Archives: Cancer Types

Anal Cancer Treatment (PDQ®)–Health Professional Version

Anal Cancer Treatment (PDQ®)–Health Professional Version

General Information About Anal Cancer

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Incidence and Mortality

Estimated new cases and deaths from anal, anal canal, and anorectal cancer in the United States in 2025:[1]

  • New cases: 10,930.
  • Deaths: 2,030.

Prognosis and Survival

The two major prognostic factors for anal cancer are tumor size and nodal status. Primary tumors smaller than 2 cm have a better prognosis.[2] Nodal drainage of the anus follows the inguinal vein. The initial evaluation of a patient with anal cancer will include a careful clinical examination of the inguinal region and biopsy of any palpable lymph nodes. For more information, see the American Joint Committee on Cancer Stage Groupings and TNM Definitions section.

Anal cancer is usually curable. At presentation, most patients have T1 or T2 disease (≤5 cm), and fewer than 20% of patients have node-positive disease. The 5-year survival rate for these early-stage patients exceeds 85%.[3,4] Even in patients with node-positive disease, 5-year survival rates exceed 50% in the absence of invasion into adjacent organs or distant metastases.[5]

Risk Factors

Overall, the risk of anal cancer is rising due to increased incidence of human papillomavirus (HPV) infection.[6,7] Ninety-five percent of anal cancers are HPV related, with the highest risk for serotypes 16 and 18. Involvement of HPV can be pathologically correlated with P16+ staining.[8] Patients with HIV have a higher risk of HPV coinfection, and consequently have a higher risk of anal cancer.

Data suggest that certain sexual practices, such as receptive anal intercourse or a high lifetime number of sexual partners, portend an increased risk of anal cancer. These practices may have led to an increase in the number of individuals at risk of infection with HPV.[6]

References
  1. American Cancer Society: Cancer Facts and Figures 2025. American Cancer Society, 2025. Available online. Last accessed January 16, 2025.
  2. Ajani JA, Winter KA, Gunderson LL, et al.: Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: the intergroup trial (RTOG 98-11). Cancer 116 (17): 4007-13, 2010. [PUBMED Abstract]
  3. Klas JV, Rothenberger DA, Wong WD, et al.: Malignant tumors of the anal canal: the spectrum of disease, treatment, and outcomes. Cancer 85 (8): 1686-93, 1999. [PUBMED Abstract]
  4. Touboul E, Schlienger M, Buffat L, et al.: Epidermoid carcinoma of the anal canal. Results of curative-intent radiation therapy in a series of 270 patients. Cancer 73 (6): 1569-79, 1994. [PUBMED Abstract]
  5. Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 275–84.
  6. Johnson LG, Madeleine MM, Newcomer LM, et al.: Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer 101 (2): 281-8, 2004. [PUBMED Abstract]
  7. Holly EA, Ralston ML, Darragh TM, et al.: Prevalence and risk factors for anal squamous intraepithelial lesions in women. J Natl Cancer Inst 93 (11): 843-9, 2001. [PUBMED Abstract]
  8. Ryan DP, Compton CC, Mayer RJ: Carcinoma of the anal canal. N Engl J Med 342 (11): 792-800, 2000. [PUBMED Abstract]

Cellular Classification of Anal Cancer

Squamous cell (epidermoid) carcinomas make up most primary anal cancers. Historically, a subset of tumors arising from the epithelial transitional zone were categorized as cloacogenic or basaloid tumors. However, these tumors are now recognized as nonkeratinizing squamous cell cancers and are similarly associated with human papillomavirus.[1,2]

Lesions in the hair-bearing skin distal to the squamous mucocutaneous junction are defined as perianal cancers. These are typically treated the same as anal canal cancers, although local therapy alone can be considered for discrete skin lesions with significant separation from the anal verge.

Adenocarcinomas starting in anal glands or fistulae formation are rare and generally have clinical features that are similar to rectal adenocarcinoma. For more information, see the Clinical Features section in Rectal Cancer Treatment.

Treatment of anal melanoma is not included in this summary.

References
  1. Palefsky JM, Holly EA, Gonzales J, et al.: Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer. Cancer Res 51 (3): 1014-9, 1991. [PUBMED Abstract]
  2. Pirog EC, Quint KD, Yantiss RK: P16/CDKN2A and Ki-67 enhance the detection of anal intraepithelial neoplasia and condyloma and correlate with human papillomavirus detection by polymerase chain reaction. Am J Surg Pathol 34 (10): 1449-55, 2010. [PUBMED Abstract]

Stage Information for Anal Cancer

The anal canal extends from the rectum to the perianal skin and is lined by a mucous membrane that covers the internal sphincter. Tumors of the anal margin (below the anal verge and involving the perianal hair-bearing skin) are classified with skin tumors.

American Joint Committee on Cancer (AJCC) Stage Groupings and TNM Definitions

The following is a staging system for anal canal cancer that has been described by the AJCC and the International Union Against Cancer.[1] The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define anal cancer.

Table 1. Definitions of TNM Stage 0a
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 275–84.
0 Tis, N0, M0 Tis = High-grade squamous intraepithelial lesion (previously termed carcinoma in situ, Bowen disease, anal intraepithelial neoplasia II–III, high-grade anal intraepithelial neoplasia).
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 2. Definitions of TNM Stage Ia
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 275–84.
I T1, N0, M0 T1 = Tumor ≤2 cm.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 3. Definitions of TNM Stages IIA and IIBa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 275–84.
IIA T2, N0, M0 T2 = Tumor >2 cm but ≤5 cm.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
IIB T3, N0, M0 T3 = Tumor >5 cm.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 4. Definitions of TNM Stages IIIA, IIIB, and IIICa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 275–84.
IIIA T1, N1, M0 T1 = Tumor ≤2 cm.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
M0 = No distant metastasis.
T2, N1, M0 T2 = Tumor >2 cm but ≤5 cm.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
M0 = No distant metastasis.
IIIB T4, N0, M0 T4 = Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
IIIC T3, N1, M0 T3 = Tumor >5 cm.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
M0 = No distant metastasis.
T4, N1, M0 T4 = Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
M0 = No distant metastasis.
Table 5. Definitions of Stage IVa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 275–84.
IV Any T, Any N, M1 TX = Primary tumor not assessed.
T0 = No evidence of primary tumor.
Tis = High-grade squamous intraepithelial lesion (previously termed carcinoma in situ, Bowen disease, anal intraepithelial neoplasia II–III, high-grade anal intraepithelial neoplasia).
T1 = Tumor ≤2 cm.
T2 = Tumor >2 cm but ≤5 cm.
T3 = Tumor >5 cm.
T4 = Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder.
NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
–N1a = Metastasis in inguinal, mesorectal, or internal iliac lymph nodes.
–N1b = Metastasis in external iliac lymph nodes.
–N1c = Metastasis in external iliac with any N1a nodes.
M1 = Distant metastasis.
References
  1. Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 275–84.

Treatment Option Overview for Anal Cancer

Treatment options for anal cancer are described in Table 6.

Table 6. Treatment Options for Anal Cancer
Stage (TNM Staging Criteria) Treatment Options
Stage 0 Surgery
Stages I, II, and III Local resection
External-beam radiation therapy with chemotherapy
Alternative strategies
Radical resection
Stage IV Palliative surgery
Palliative radiation therapy
Palliative chemotherapy (with or without radiation therapy)
Checkpoint inhibitors

The optimal approach in patients with advanced disease is still under clinical evaluation. Information about ongoing clinical trials is available from the NCI website.

Capecitabine and Fluorouracil Dosing

The DPYD gene encodes an enzyme that catabolizes pyrimidines and fluoropyrimidines, like capecitabine and fluorouracil. An estimated 1% to 2% of the population has germline pathogenic variants in DPYD, which lead to reduced DPD protein function and an accumulation of pyrimidines and fluoropyrimidines in the body.[1,2] Patients with the DPYD*2A variant who receive fluoropyrimidines may experience severe, life-threatening toxicities that are sometimes fatal. Many other DPYD variants have been identified, with a range of clinical effects.[1–3] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient’s DPYD genotype and number of functioning DPYD alleles.[4–6] DPYD genetic testing costs less than $200, but insurance coverage varies due to a lack of national guidelines.[7] In addition, testing may delay therapy by 2 weeks, which would not be advisable in urgent situations. This controversial issue requires further evaluation.[8]

References
  1. Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021. [PUBMED Abstract]
  2. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
  3. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [PUBMED Abstract]
  4. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [PUBMED Abstract]
  5. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [PUBMED Abstract]
  6. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [PUBMED Abstract]
  7. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [PUBMED Abstract]
  8. Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023. [PUBMED Abstract]

Treatment of Stage 0 Anal Cancer

Treatment Options for Stage 0 Anal Cancer

Stage 0 anal cancer is carcinoma in situ. Rarely diagnosed, it is a very early cancer that has not spread below the limiting membrane of the first layer of anal tissue.

Treatment options for stage 0 anal cancer include:

  1. Surgical resection is used to treat lesions of the perianal area not involving the anal sphincter. The surgical approach depends on the location of the lesion in the anal canal.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Treatment of Stages I, II, and III Anal Cancer

Treatment Options for Stages I, II, and III Anal Cancer

Current sphincter-sparing therapies include wide local excision for small tumors of the perianal skin or anal margin, or definitive chemoradiation therapy (fluorouracil [5-FU] and mitomycin) for cancers of the anal canal. Radical resection is reserved for patients with incomplete responses or recurrent disease.

Continued surveillance with rectal examination every 3 months for the first 2 years and endoscopy with biopsy when indicated after completion of sphincter-preserving therapy is important to monitor for recurrence.

Treatment options for stage I, stage II, and stage III anal cancer include:

  1. Small tumors of the perianal skin or anal margin not involving the anal sphincter may be adequately treated with local resection.[1]
  2. The standard of care for all other stage I, II, and III anal cancers in appropriate patients is chemoradiation therapy (external-beam radiation therapy [EBRT] with chemotherapy).
    • 5-FU + mitomycin + radiation therapy.[2,3]
    • Capecitabine + mitomycin + radiation therapy.[4,5]
    • 5-FU + cisplatin + radiation therapy.[6,7]
  3. Alternative strategies such as radiation therapy alone or surgery alone may be considered, depending on the clinical context.
  4. Radical resection is reserved for residual or recurrent cancer in the anal canal after nonoperative therapy.

Chemoradiation therapy

Because of historically high rates of recurrence with colostomy alone, chemoradiation therapy is the preferred approach for patients with anal cancer in the absence of distant metastases.

Evidence (chemoradiation therapy):

  1. The Anal Cancer Trial (ACT I) from the United Kingdom Co-ordinating Committee on Cancer Research demonstrated the superiority of chemoradiation with 5-FU and mitomycin over radiation therapy alone with regard to local failure and deaths from anal cancer.[2,8][Level of evidence A1]

    In this prospective trial, 585 patients were randomly assigned to receive 45 Gy of radiation in 20 or 25 fractions with or without 5-FU. The 5-FU was given by continuous infusion (750 mg/m2 for 5 days or 1,000 mg/m2 for 4 days) during the first and final weeks of radiation therapy, along with a single dose of mitomycin (12 mg/m2) on the first day.

    • After a median follow-up of 13.1 years, patients who received chemoradiation therapy had a reduction in local failure (36% vs. 59%; hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.35−0.60; P < .001), risk of death from anal cancer (HR, 0.61; 95% CI, 0.49−0.76; P < .001), and relapse at 12 years (17.7% vs. 29.7%; HR, 0.70; 95% CI, 9.58−0.84; P < .001).[2][Level of evidence A1]
    • There was no significant difference in overall survival (OS) in this trial (HR, 0.86; 95% CI, 0.70−1.04; P = .12).
    • An initial 9.1% increase in non–anal cancer deaths was observed in the first 5 years after chemoradiation therapy but was not seen at 10 years.
  2. A European Organisation for Research and Treatment of Cancer (EORTC) trial prospectively randomly assigned 100 patients with T3 to T4 or N1 to N3 disease to receive 45 Gy of radiation with a 15-Gy or 30-Gy boost with or without 5-FU infusion (750 mg/m2 for 5 days starting on days 1 and 29) plus mitomycin (15 mg/m2 on day 1).[3][Level of evidence B1]
    • Outcomes favored chemoradiation therapy with respect to 5-year colostomy-free survival rates (75% vs. 48%; P = .002) and 5-year progression-free survival (PFS) rates (60% vs. 48%; P = .05).

Subsequent trials have found capecitabine to be a reasonable replacement for 5-FU in combination with mitomycin and radiation therapy.[4,5]

While the ACT I and EORTC randomized trials established chemoradiation therapy as the preferred approach for nonmetastatic anal cancer, the substantial hematological, renal, and pulmonary toxicity of mitomycin has prompted studies of alternative regimens.

Evidence (chemoradiation therapy [alternative regimens]):

  1. A Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group trial of 310 patients studied chemoradiation therapy (5-FU infusion + 45 Gy of radiation) with or without mitomycin.
    • After 4-years of follow-up, patients who received mitomycin had an improved colostomy-free survival rate (71% vs. 59%; P = .014) and disease-free survival (DFS) rate (73% vs. 51%; P = .0003).[9][Level of evidence B1]

    Two large intergroup trials studied the substitution of cisplatin for mitomycin, with differing conclusions.

  2. In a phase III U.S. Intergroup trial (RTOG 9811 [NCT00003596]), patients in the cisplatin arm received two cycles of induction 5-FU and cisplatin before receiving concurrent chemoradiation therapy with 5-FU and cisplatin.[6]
    • Patients who received mitomycin had improved local control and an improved colostomy-free survival rate (90% vs. 81%; P = .02). Subsequent long-term follow-up demonstrated a borderline significant difference in the 5-year colostomy-free survival rate (71.9% vs. 65%; P = .05).[10]
    • Long-term follow-up also demonstrated a superior 5-year DFS rate (67.8% vs. 57.8%; P = .006) and OS rate (78.3% vs. 70.7%; P = .074) for patients who received mitomycin.[11][Level of evidence B1]
    • One potential explanation for the inferiority of cisplatin in this study was the delay in time to radiation therapy during induction chemotherapy.
  3. In the prospective randomized ACT II trial, 940 patients were assigned in a 2 × 2 factorial design to receive the following: (1) either mitomycin or cisplatin during induction chemoradiation therapy and (2) either maintenance therapy with 5-FU and cisplatin in weeks 11 and 14 or no maintenance therapy.[7]
    • The complete remission rate was equivalent in patients who received mitomycin or cisplatin after a median follow-up of 5.1 years (90.5% vs. 89.6%; 95% CI, -4.9 to 3.1; P = .64). The 3-year PFS rate was also equivalent in both study groups (73% for mitomycin vs. 72% for cisplatin; HR, 0.95; 95% CI, 0.75−1.19; P = .063).[7][Level of evidence B1]
    • There was also no significant effect on 3-year PFS rates among patients who received maintenance therapy or no maintenance therapy (74% vs. 73%; HR, 0.95; 95% CI, 0.75−1.21; P = .70).
    • This study suggests that cisplatin might reasonably substitute for mitomycin in a chemoradiation strategy.

The best time to assess a complete clinical response after chemoradiation therapy is generally after 26 weeks because delayed responses are seen.[12] Residual disease or subsequent local recurrence require further treatment.

The standard salvage therapy for patients with either gross or microscopic residual disease after chemoradiation therapy has been abdominoperineal resection. Alternatively, patients may be treated with additional salvage chemoradiation therapy, chemotherapy alone, or immunotherapy.[12,13]

The optimal radiation dose in various situations has not been determined. There is insufficient evidence to determine whether the dose should be escalated for patients with T3 to T4 disease or nodal metastases, or potentially de-escalated for patients with early-stage tumors smaller than 1 cm. It is also unclear whether the chemotherapy backbone can be safely omitted for some patients with early-stage tumors, and whether such a strategy would affect the optimal dose of radiation. The roles for newer strategies such as intensity-modulated radiation therapy, proton beam therapy, and brachytherapy have yet to be conclusively determined.[14–16] Based on the National Cancer Database, higher volume radiation oncology centers report improved OS for patients with anal cancer.[17]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References
  1. Enker WE, Heilwell M, Janov AJ, et al.: Improved survival in epidermoid carcinoma of the anus in association with preoperative multidisciplinary therapy. Arch Surg 121 (12): 1386-90, 1986. [PUBMED Abstract]
  2. Northover J, Glynne-Jones R, Sebag-Montefiore D, et al.: Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer 102 (7): 1123-8, 2010. [PUBMED Abstract]
  3. Bartelink H, Roelofsen F, Eschwege F, et al.: Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 15 (5): 2040-9, 1997. [PUBMED Abstract]
  4. Goodman KA, Julie D, Cercek A, et al.: Capecitabine With Mitomycin Reduces Acute Hematologic Toxicity and Treatment Delays in Patients Undergoing Definitive Chemoradiation Using Intensity Modulated Radiation Therapy for Anal Cancer. Int J Radiat Oncol Biol Phys 98 (5): 1087-1095, 2017. [PUBMED Abstract]
  5. Meulendijks D, Dewit L, Tomasoa NB, et al.: Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option. Br J Cancer 111 (9): 1726-33, 2014. [PUBMED Abstract]
  6. Ajani JA, Winter KA, Gunderson LL, et al.: Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299 (16): 1914-21, 2008. [PUBMED Abstract]
  7. James RD, Glynne-Jones R, Meadows HM, et al.: Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol 14 (6): 516-24, 2013. [PUBMED Abstract]
  8. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 348 (9034): 1049-54, 1996. [PUBMED Abstract]
  9. Flam M, John M, Pajak TF, et al.: Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14 (9): 2527-39, 1996. [PUBMED Abstract]
  10. Eng C, Ciombor KK, Cho M, et al.: Anal Cancer: Emerging Standards in a Rare Disease. J Clin Oncol 40 (24): 2774-2788, 2022. [PUBMED Abstract]
  11. Gunderson LL, Winter KA, Ajani JA, et al.: Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol 30 (35): 4344-51, 2012. [PUBMED Abstract]
  12. Pedersen TB, Gocht-Jensen P, Klein MF: 30-day and long-term outcome following salvage surgery for squamous cell carcinoma of the anus. Eur J Surg Oncol 44 (10): 1518-1521, 2018. [PUBMED Abstract]
  13. Guerra GR, Kong JC, Bernardi MP, et al.: Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma. Dis Colon Rectum 61 (2): 179-186, 2018. [PUBMED Abstract]
  14. Cordoba A, Escande A, Leroy T, et al.: Low-dose-rate interstitial brachytherapy boost for the treatment of anal canal cancers. Brachytherapy 16 (1): 230-235, 2017 Jan – Feb. [PUBMED Abstract]
  15. Call JA, Prendergast BM, Jensen LG, et al.: Intensity-modulated Radiation Therapy for Anal Cancer: Results From a Multi-Institutional Retrospective Cohort Study. Am J Clin Oncol 39 (1): 8-12, 2016. [PUBMED Abstract]
  16. Gryc T, Ott O, Putz F, et al.: Interstitial brachytherapy as a boost to patients with anal carcinoma and poor response to chemoradiation: Single-institution long-term results. Brachytherapy 15 (6): 865-872, 2016 Nov – Dec. [PUBMED Abstract]
  17. Amini A, Jones BL, Ghosh D, et al.: Impact of facility volume on outcomes in patients with squamous cell carcinoma of the anal canal: Analysis of the National Cancer Data Base. Cancer 123 (2): 228-236, 2017. [PUBMED Abstract]

Treatment of Stage IV Anal Cancer

Treatment Options for Stage IV Anal Cancer

Treatment options for stage IV anal cancer include:

  1. Palliative surgery.
  2. Palliative radiation therapy.
  3. Palliative chemotherapy (with or without radiation therapy).
    • Cisplatin + infusional fluorouracil (5-FU).[1]
    • Carboplatin + weekly paclitaxel.[2]
    • Docetaxel + cisplatin + 5-FU.[3]
    • Nivolumab.[4]
    • Pembrolizumab.[5]
  4. Checkpoint inhibitors.

Advanced-stage therapy

  1. In the multicenter, randomized, phase II International Advanced Anal Cancer InterAACT trial (NCT02560298), carboplatin (area under the curve 5) and weekly paclitaxel was compared with standard infusional 5-FU and bolus cisplatin in patients with advanced-stage anal cancer.[2]
    • With a median follow-up of 25.3 months, the median overall survival (OS) with carboplatin and paclitaxel was improved compared with cisplatin and 5-FU (20 months vs. 12.3 months; hazard ratio [HR], 2.0; P = .014).[Level of evidence A1]
    • Serious adverse events were more common in patients treated with cisplatin plus 5-FU (62% vs. 36%; P = .016).

    These promising findings have led international investigators to use carboplatin and paclitaxel as a new backbone in trials for patients with advanced-stage disease, as well as a potential partner for use with radiation therapy. Other chemotherapy regimens, such as modified docetaxel, cisplatin, and 5-FU, are under clinical evaluation.[3]

  2. The checkpoint inhibitors have also shown activity for patients with metastatic disease. The phase II NCI96773 trial (NCT02314169) of single-agent nivolumab (3 mg/kg every 2 weeks) enrolled 37 patients.[4]
  3. The phase Ib KEYNOTE-028 trial (NCT02054806) for patients with advanced tumors with programmed death ligand-1 of at least 1% enrolled a cohort of 24 patients with anal squamous cell carcinoma.[5]
    • The overall response rate was 17%, and an additional stable disease rate was 42%.[5][Level of evidence C3]

Although there is no clear standard of care for patients with metastatic disease, recent studies are uncovering promising new avenues for systemic treatment. Palliation of symptoms from the primary lesion is important. Patients with stage IV disease should strongly consider enrolling in clinical trials.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References
  1. James RD, Glynne-Jones R, Meadows HM, et al.: Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol 14 (6): 516-24, 2013. [PUBMED Abstract]
  2. Rao S, Sclafani F, Eng C, et al.: International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct. J Clin Oncol 38 (22): 2510-2518, 2020. [PUBMED Abstract]
  3. Kim S, François E, André T, et al.: Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol 19 (8): 1094-1106, 2018. [PUBMED Abstract]
  4. Morris VK, Salem ME, Nimeiri H, et al.: Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol 18 (4): 446-453, 2017. [PUBMED Abstract]
  5. Ott PA, Piha-Paul SA, Munster P, et al.: Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol 28 (5): 1036-1041, 2017. [PUBMED Abstract]

Treatment of HIV and Anal Cancer

The tolerance of patients with HIV and anal carcinoma to standard fluorouracil and mitomycin chemoradiation therapy is not well defined.[1,2] In general, patients with HIV are treated similarly to other patients and have similar outcomes, particularly in the era of highly active antiretroviral therapy (HAART). Patients with pretreatment CD4 counts of fewer than 200 cells/μl may have increased acute and late toxic effects.[3,4] Therefore, patients with a history of AIDS-related complications may have difficulty tolerating a standard regimen, necessitating a dose adjustment or omission of mitomycin.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References
  1. Holland JM, Swift PS: Tolerance of patients with human immunodeficiency virus and anal carcinoma to treatment with combined chemotherapy and radiation therapy. Radiology 193 (1): 251-4, 1994. [PUBMED Abstract]
  2. Peddada AV, Smith DE, Rao AR, et al.: Chemotherapy and low-dose radiotherapy in the treatment of HIV-infected patients with carcinoma of the anal canal. Int J Radiat Oncol Biol Phys 37 (5): 1101-5, 1997. [PUBMED Abstract]
  3. Hoffman R, Welton ML, Klencke B, et al.: The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer. Int J Radiat Oncol Biol Phys 44 (1): 127-31, 1999. [PUBMED Abstract]
  4. Place RJ, Gregorcyk SG, Huber PJ, et al.: Outcome analysis of HIV-positive patients with anal squamous cell carcinoma. Dis Colon Rectum 44 (4): 506-12, 2001. [PUBMED Abstract]

Treatment of Recurrent Anal Cancer

Local recurrences and persistent disease after treatment with radiation therapy and chemotherapy or surgery as the primary treatment may be controlled by using the alternate treatment (surgical resection after radiation and vice versa).[1] Salvage chemoradiation therapy with fluorouracil and cisplatin plus a radiation boost may avoid permanent colostomy in patients with residual tumor after initial nonoperative therapy.[2] Clinical trials are exploring the use of radiation therapy with chemotherapy and radiosensitizers to improve local control.

Preliminary studies in patients with stage IV disease suggest that alternative chemotherapy regimens (such as carboplatin and paclitaxel in the InterACCT trial [NCT02560298]) or immune checkpoint inhibitors (as in NCI9673 [NCT02314169] and KEYNOTE-028 [NCT02054806]) may be beneficial in this setting.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References
  1. Longo WE, Vernava AM, Wade TP, et al.: Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy. Ann Surg 220 (1): 40-9, 1994. [PUBMED Abstract]
  2. Flam M, John M, Pajak TF, et al.: Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14 (9): 2527-39, 1996. [PUBMED Abstract]

Latest Updates to This Summary (02/12/2025)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Anal Cancer

Updated statistics with estimated new cases and deaths for 2025 (cited American Cancer Society as reference 1).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of anal cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Anal Cancer Treatment are:

  • Amit Chowdhry, MD, PhD (University of Rochester Medical Center)
  • Leon Pappas, MD, PhD (Massachusetts General Hospital)
  • Ari Seifter, MD (Advocate Health Care)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website’s Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Anal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: /types/anal/hp/anal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389221]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.

Anal Cancer—Patient Version

Anal Cancer—Patient Version

Overview

Anal cancer cases have been increasing over several decades. Infection with human papillomavirus (HPV) is the major risk factor for anal cancer. Explore the links on this page to learn more about anal cancer prevention, treatment, statistics, research, and clinical trials.

Treatment

PDQ Treatment Information for Patients

More information

Causes & Prevention

PDQ Prevention Information for Patients

More information

Screening

NCI does not have PDQ evidence-based information about screening for anal cancer.

More information

Statistics

Coping with Cancer

The information in this section is meant to help you cope with the many issues and concerns that occur when you have cancer.

Emotions and Cancer Adjusting to Cancer Support for Caregivers Survivorship Advanced Cancer Managing Cancer Care

Research

Anal Cancer Advances Open Door to Screening and Prevention

In People with HIV, Treating Precancerous Anal Lesions Cuts Risk of Anal Cancer By More Than Half

Anal Cancer Incidence and Deaths Are Rising in the United States

DCEG Studies About Anal Cancer

Prostate Cancer Research Results and Study Updates

Prostate Cancer Research Results and Study Updates

See Advances in Prostate Cancer Research for an overview of recent findings and progress, plus ongoing projects supported by NCI.

Advances in Prostate Cancer Research

Advances in Prostate Cancer Research

Prostate cancer cells interacting with polymeric nanoparticles coated with targeting molecules.

Nanoparticles are tested as a means to deliver drugs to prostate cancer cells.

Credit: National Cancer Institute

NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat prostate cancer.  Most men diagnosed with prostate cancer will live a long time, but challenges remain in choosing the best treatments for individuals at all stages of the disease.

This page highlights some of the latest research in prostate cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Studying Early Detection for Men at High Risk

Men with certain inherited genetic traits are at increased risk for developing prostate cancer. Examples of such traits include inherited BRCA gene mutations and Lynch syndrome. No clear guidelines exist for when or how—or if—to screen men at high genetic risk for prostate cancer. 

NCI researchers are using magnetic resonance imaging (MRI) of the prostate in men at high risk of developing prostate cancer to learn more about how often and how early these cancers occur. They’re also testing whether regular scans in such men can detect cancers early, before they spread elsewhere in the body (metastasize).

Diagnosing Prostate Cancer

Improving biopsies for prostate cancer

Traditionally, prostate cancer has been diagnosed using needles inserted into the prostate gland in several places under the guidance of transrectal ultrasound (TRUS) imaging to collect samples of tissue. This approach is called systematic biopsy.

However, ultrasound does not generally show the location of cancer within the prostate. It is mainly used to make sure the biopsy needles go into the gland safely. Therefore, biopsy samples using ultrasound guidance can miss cancer altogether. Or they may identify low-grade cancer while missing areas of high-grade, potentially more aggressive cancer, particularly in Black men.

Some doctors, concerned that a systematic biopsy showing only low-grade cancer could have missed a high-grade cancer, may suggest surgery or radiation. However, in some cases these treatments will be for a cancer that may have never caused a problem, which is considered overtreatment.

Using MRI and ultrasound. Scientists at NCI have developed a procedure that combines magnetic resonance imaging (MRI) with TRUS for more accurate prostate biopsies. MRI can locate potential areas of cancer within the gland but is not practical for real-time imaging to guide a prostate biopsy. The procedure, known as MRI-targeted biopsy, uses computers to fuse an MRI image with an ultrasound image. This lets doctors use ultrasound guidance to take biopsy samples of areas of possible cancer seen on MRI.

NCI researchers have found that combining MRI-targeted biopsy with systematic biopsy can increase the detection of high-grade prostate cancers while decreasing detection of low-grade cancers that are unlikely to progress. 

Testing machine learning. Researchers are testing the use of machine learning, also called artificial intelligence (AI), to better recognize suspicious areas in a prostate MRI that should be biopsied. AI is also being developed to help pathologists who aren’t prostate cancer experts accurately assess prostate cancer grade. Cancer grade is the most important factor in determining the need for treatment versus active surveillance.

Finding small amounts of prostate cancer using imaging and PSMA

NCI-supported researchers are developing new imaging techniques to improve the diagnosis of recurrent prostate cancer. A protein called prostate-specific membrane antigen (PSMA) is found in large amounts—and almost exclusively—on both cancerous and noncancerous prostate cells. By fusing a molecule that binds to PSMA to a compound used in PET imaging, scientists have been able to see tiny deposits of prostate cancer that are too small to be detected by regular imaging.

The Food and Drug Administration (FDA) has approved two such compounds for use in PSMA-PET imaging of men with prostate cancer. These approvals are for men whose cancer may have spread to other parts of the body but is still considered curable, either with surgery or other treatments.

The ability to detect very small amounts of metastatic prostate cancer could help doctors and patients make better-informed treatment decisions. For example, if metastatic cancer is found when a man is first diagnosed, he may choose an alternative treatment to surgery because the cancer has already spread. Or doctors may be able to treat cancer recurrence—either in the prostate or metastatic disease—earlier, which may lead to better survival. Studies are being done to determine if such early detection can improve outcomes.

As part of the Cancer Moonshot℠, NCI researchers are testing whether PSMA-PET imaging can also identify men who are at high risk of their cancer recurring. Such imaging may eventually be able to help predict who needs more aggressive treatment—such as radiation therapy in addition to surgery—after diagnosis.

Research teams are also looking at:

New Prostate Cancer Treatments

Standard treatments for prostate cancer that has not spread elsewhere in the body are surgery or radiation therapy, with or without hormone therapy. 

Active surveillance is also an option for men who have a low risk of their cancer spreading. This means monitoring the cancer with regular biopsies and other tests, and holding off on treatment unless there is evidence of progression. Rates of active surveillance more than doubled between 2014 and 2021, to almost 60% of US men diagnosed with low-risk prostate cancer. 

Hormone therapy for prostate cancer

Over the last decade, several new approaches to hormone therapy for advanced or metastatic prostate cancer have been approved for clinical use.

Many prostate cancers that originally respond to treatment with standard hormone therapy become resistant over time, resulting in castrate-resistant prostate cancer (CRPC). Four newer drugs have been shown to extend survival in some groups of men with CRPC. All inhibit the action of hormones that drive CRPC:

These drugs are now also used in some people whose prostate cancer still responds to standard hormone therapies but has spread elsewhere in the body (metastasized).

Scientists are continuing to study novel treatments and drugs, along with new combinations of existing treatments, in men with metastatic and castrate-resistant prostate cancer.

Hormone therapy for biochemically recurrent prostate cancer

A biochemical recurrence is a rise in the blood level of PSA in people with prostate cancer after treatment with surgery or radiation. In 2023, the FDA approved enzalutamide, given alone or with another drug called leuprolide, for some men who have a biochemical recurrence and are at high risk of their cancer spreading but don’t have signs on regular imaging that their cancer has come back.

Use of this drug combination can improve how long these men live without their cancer spreading. But it’s not yet known if using the drugs in this manner improves how long people live overall. Researchers are trying to determine which patients will benefit most from these types of treatments.

PARP inhibitors for prostate cancer

A PARP inhibitor is a substance that blocks an enzyme in cells called PARP. PARP helps repair DNA when it becomes damaged. Some prostate tumors have genetic changes that limit their ability to repair DNA damage. These tumors may be sensitive to treatment with PARP inhibitors. Some people also inherit genetic factors that limit their body’s ability to repair DNA damage. Prostate tumors in such people can also be treated with PARP inhibitors.  

Two PARP inhibitors, olaparib (Lynparza) and rucaparib (Rubraca), have been approved for use alone in some men whose prostate cancer has such genetic changes and has metastasized, and whose disease has stopped responding to standard hormone treatments alone.

Ongoing studies are looking at combining PARP inhibitors with hormone therapies. Since 2023, the FDA has approved three such combinations for some men with metastatic prostate cancer:

Immunotherapy: vaccines for prostate cancer

Immunotherapies are treatments that harness the power of the immune system to fight cancer. These treatments can either help the immune system attack the cancer directly or stimulate the immune system in a more general way.

Vaccines and checkpoint inhibitors are two types of immunotherapy being tested in prostate cancer. Treatment vaccines are injections that stimulate the immune system to recognize and attack a tumor.

One type of treatment vaccine called sipuleucel-T (Provenge) is approved for men with few or no symptoms from metastatic CRPC.

Immunotherapy: checkpoint inhibitors for prostate cancer

An immune checkpoint inhibitor is a type of drug that blocks proteins on immune cells, making the immune system more effective at killing cancer cells.

Two checkpoint inhibitors, pembrolizumab (Keytruda) and dostarlimab (Jemperli) have been approved for the treatment of tumors, including prostate cancers, that have specific genetic features. Pembrolizumab has also been approved for any tumor that has metastasized and has a high number of genetic mutations.

But relatively few prostate cancers have these features, and prostate cancer in general has largely been resistant to treatment with checkpoint inhibitors and other immunotherapies, such as CAR T-cell therapy.

Research is ongoing to find ways to help the immune system recognize prostate tumors and help immune cells penetrate prostate tumor tissue. Studies are looking at whether combinations of immunotherapy drugs, or immunotherapy drugs given with other types of treatment, may be more effective in treating prostate cancer than single immunotherapies alone.

PSMA-targeted radiation therapy

Scientists have developed targeted therapies based on PSMA, the same protein that is used for imaging prostate cancer. For treatment, the molecule that targets PSMA is chemically linked to a radioactive substance. This new compound can potentially find, bind to, and kill prostate cancer cells throughout the body.

In a recent clinical trial, men with a type of advanced prostate cancer who received a PSMA-targeting drug lived longer than those who received standard therapies. This trial led to FDA approval of the drug, Lu177-PSMA-617 (Pluvicto), to treat some people with metastatic prostate cancer who had previously received chemotherapy. 

An ongoing study is testing the use of Lu177-PSMA-617 in some people with metastatic prostate cancer who haven’t yet received chemotherapy. Other clinical trials are testing PSMA-targeting drugs in patients with earlier stages of prostate cancer, and in combination with other treatments, including targeted therapies like PARP inhibitors and immunotherapy.

Personalized clinical trials for prostate cancer

Research is uncovering more information about the genetic changes that happen as prostate cancers develop and progress. Although early-stage prostate cancer has relatively few genetic changes compared with other types of cancer, researchers have learned that metastatic prostate cancers usually accumulate more changes as they spread through the body.

These changes may make men with metastatic prostate cancers candidates for what are called “basket” clinical trials of new drugs. Such trials enroll participants based on the changes found in their cancer, not where in the body the cancer arose. In the NCI-MATCH trial, a high percentage of enrolled men with advanced prostate cancer had genetic changes that could potentially be targeted with investigational drugs.

NCI-Supported Research Programs

Many NCI-funded researchers working at the National Institutes of Health campus, as well as across the United States and world, are seeking ways to address prostate cancer more effectively. Some of this research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in prostate cancer.

  • The Cancer Biomarkers Research Group promotes research on cancer biomarkers and manages the Early Detection Research Network (EDRN). EDRN is a network of NCI-funded institutions that are collaborating to discover and validate early detection biomarkers.
  • Within the Center for Cancer Research, the Prostate Cancer Multidisciplinary Clinic (PCMC) provides comprehensive consultations on diagnosis and treatment options to people with newly-diagnosed prostate cancer. 
  • The Prostate Specialized Programs of Research Excellence (Prostate SPOREs) are designed to quickly move basic scientific findings into clinical settings. The Prostate SPOREs support the development of new therapies and technologies and studies to better understand how to prevent, monitor, and treat prostate cancer.
  • The NCI Cancer Intervention and Surveillance Modeling Network (CISNET) focuses on using modeling to improve our understanding of which men are most likely to benefit from PSA-based screening. CISNET also studies treatment strategies for prostate cancer and approaches for reducing prostate cancer disparities.
  • The NCI Genitourinary Malignancies Center of Excellence (GUM-COE) brings together scientists studying genitourinary cancers (GU) from across NCI’s Center for Cancer Research and the Division of Cancer Epidemiology and Genetics, as well as investigators who study GU malignancies in other institutes of NIH. The goal is to provide a centralized resource and infrastructure to accelerate the discovery, development, and delivery of interventions for the prevention, diagnosis, and treatment of these cancers.
  • The Research on Prostate Cancer in Men with African Ancestry (RESPOND) study is the largest-ever coordinated research effort to study biological and non-biological factors associated with aggressive prostate cancer in African American men. The study, launched by NCI and the National Institute on Minority Health and Health Disparities in partnership with the Prostate Cancer Foundation, is looking at the environmental and genetic factors related to the aggressiveness of prostate cancer in African American men to better understand why they disproportionally experience aggressive disease.

Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for prostate cancer prevention, screening, and treatment.

Prostate Cancer Research Results

The following are some of our latest news articles on prostate cancer research:

View the full list of Prostate Cancer Research Results and Study Updates.

Understanding Prostate Changes and Conditions

Understanding Prostate Changes and Conditions

Black male consulting with doctor.

Take charge of your health. Talk with your doctor about how prostate problems are treated.

Prostate changes and conditions that are common in men include inflammation (prostatitis), enlarged prostate (benign prostatic hyperplasia (BPH), and prostate cancer. Learn about prostate health including prostate-related symptoms, diagnostic tests, and treatments that your doctor may suggest for prostate issues.

About the prostate and prostate changes

The prostate is part of the male reproductive system. The prostate tends to grow larger as a man ages. When men are in their 20s, the normal prostate is about the size of a walnut. By the time a man is 40 the prostate may have grown slightly larger, and by age 60, the prostate is often the size of a lemon. Age increases the risk of prostate problems, such as BPH and prostate cancer.

Anatomy of the male reproductive and urinary systems showing the prostate, testicles, bladder, and other organs. Enlarge

Anatomy of the male reproductive and urinary systems showing the prostate, testicles, bladder, and other organs.

Where is the prostate located? 

The prostate gland is located below the bladder and in front of the rectum. The prostate surrounds part of the urethra, a tube that carries urine out of the bladder and through the penis.

What does the prostate do?

The prostate is a gland that helps make semen, the white, milky fluid that carries sperm when a man ejaculates. Muscles in the prostate push semen into the urethra and out, through ejaculation.

What are symptoms of prostate changes? 

Benign prostate conditions can cause symptoms such as frequent or the sudden need to urinate (pee) especially at night, pain or burning while urinating, a weak stream of urine, difficulty urinating, blood in the urine or semen, and painful ejaculation.

What tests are used to diagnose prostate problems?

Diagnostic tests can determine if your symptoms are caused by prostate cancer, a benign prostate condition, or other condition such as a urinary tract infection (UTI). Your doctor will do a physical exam and ask about symptoms such as pain, fever, or trouble passing urine—as well as how long you’ve had these problems and how much they are affecting you.

What to expect during a prostate exam

Based on your symptoms, your doctor may advise a digital rectal exam, blood tests such as the prostate-specific antigen (PSA) test, and a urinalysis. Your doctor may refer you to a urologist, a doctor who specializes in diagnosing and treating diseases of the urinary and reproductive organs in males and the urinary organs in females. Learn more about prostate tests that may be used to check for prostate problems.

If you have a PSA test and your PSA level is high, your doctor will talk with you about next steps. A high PSA level can be caused by many things, including:

  • some benign prostate conditions
  • urinary tract infections
  • having a digital rectal exam
  • having a prostate biopsy
  • disturbance to the prostate (from bike riding, for example)
  • prostate cancer

Learn more about the PSA test.

What is prostatitis?

Prostatitis is a benign condition that involves inflammation of the prostate. Prostatitis does not increase your risk of prostate cancer. It is the most common urinary condition in men younger than age 50 and affects at least half of all men at some time during their lives. Prostatitis can raise a man’s PSA level.

Signs and symptoms of types of prostatitis

There are four major types of prostatitis. Each type has unique symptoms and causes.

Acute bacterial prostatitis is caused by a bacterial infection. It is the least common type of prostatitis. Symptoms begin suddenly, get worse quickly, and may include

  • fever, chills, body aches, nausea, or vomiting
  • burning when urinating, frequent, sudden, or urgent need to urinate (pee), difficulty urinating, or a weak urine stream 
  • pain in your lower belly (abdomen), groin, genitals, or lower back

Sometimes this type of prostatitis can block the urinary tract, and you may be unable to urinate. Seek treatment right away for symptoms of acute bacterial prostatitis.

Chronic bacterial prostatitis is also caused by a bacterial infection. Symptoms are similar to those of acute bacterial prostatitis but are less severe. Unlike acute bacterial prostatitis, chronic bacterial prostatitis symptoms may come and go or get worse slowly, over several months. Men with chronic bacterial prostatitis often have urinary tract infections (UTIs) that keep coming back after treatment.

Chronic prostatitis/chronic pelvic pain syndrome is diagnosed in men of all ages who have pain that lasts more than three months, including:

  • pain in the genital area, lower abdomen, or lower back
  • pain when urinating, the need to urinate often, or a weak flow of urine

It is the most common but least understood type of prostatitis. Infection-fighting cells (white blood cells) are often found in the prostate fluid and semen.

Asymptomatic inflammatory prostatitis doesn’t cause symptoms, although white blood cells are detected in the prostate fluid and semen. This condition is often found during testing for other conditions, such as infertility or prostate cancer.

Learn about treatment for different types of prostatitis.

What is benign prostatic hyperplasia (BPH)?

Benign prostatic hyperplasia (BPH) (also called an enlarged prostate) is an overgrowth of prostate tissue. Its name comes from benign (not cancer) and hyperplasia, which means there are an increased number of cells in the prostate gland.

Signs and symptoms of an enlarged prostate (BPH)

Illustration showing the difference between a normal prostate and an enlarged prostate

Normal prostate and benign prostatic hyperplasia (BPH). A normal prostate does not block the flow of urine from the bladder. An enlarged prostate presses on the bladder and urethra and blocks the flow of urine.

Because an enlarged prostate can push against the urethra and the bladder, it may cause urinary symptoms, such as:

  • the need to urinate more often, especially at night 
  • pushing or straining to begin a urine stream
  • feeling that the bladder has not fully emptied
  • the strong or sudden need to urinate
  • weak, slow, or dribbling stream of urine
  • trouble urinating; stopping and starting multiple times while passing urine
  • painful urination
  • pain after ejaculation
  • blood in the urine

Symptoms related to BPH are one of the most common reasons that older men make an appointment to see a urologist.

An enlarged prostate does not increase a man’s risk for prostate cancer. However, people with an enlarged prostate have an increased risk of prostatitis. Over time, if it’s not treated, BPH can lead to a weak bladder, a backflow of urine that can cause bladder or kidney infections, or a blocked flow of urine, which can cause kidney failure.

Treatment for an enlarged prostate  

Although BPH cannot be cured, medicine or surgery can reduce symptoms and help you feel better. Your doctor will talk with you about treatment options, which are based on the results of medical tests, the size of the prostate, your overall health, and your personal preferences.

If your symptoms are mild, your doctor may advise practical steps you can take at home, such as drinking less fluids, especially those with alcohol or caffeine, before bedtime. You may also read about herbal or natural remedies. But such remedies may not help and can possibly cause harm. Before trying any supplements, you should check with your doctor. Their advice may depend on other medications you take and your personal medical history.

Your doctor may also suggest medications. Drugs such as alpha-blockers may be used to relax the muscles near the prostate, and 5-alpha reductase inhibitors may be used to shrink the prostate gland. For severe BPH symptoms or if medicine has not worked well, your doctor may talk with you about minimally invasive procedures or surgery.

Learn more about treatment options for benign prostatic hyperplasia (BPH) and about ongoing BPH clinical trials.

What is prostate cancer?

Prostate cancer is cancer that forms in tissues of the prostate. 

Prostate cancer risk factors

Illustration of the anatomy of prostate with cancer

Risk factors for prostate cancer include:

  • being 50 years or older
  • having a first-degree relative (a father, brother, or son) with prostate cancer
  • inherited gene changes, such as having BRCA1 or BRCA2 gene mutation or Lynch syndrome
  • race and ethnicity; prostate cancer develops more often in African American men
  • history of smoking

BPH and prostatitis are not risk factors for prostate cancer. Learn more about risk factors and protective factors for prostate cancer.

Can prostate cancer be detected early?

PSA testing is sometimes used to screen for prostate cancer. There are both possible benefits and harms to screening, and men who are considering screening should talk with their doctor to see if screening is right for them. Learn more about the prostate-specific antigen (PSA) test.

Symptoms of prostate cancer 

Early-stage prostate cancer does not usually cause symptoms. However, locally advanced prostate cancer may cause urinary symptoms including blood in the urine or semen or pain in the back, hips, or pelvis that doesn’t go away. Learn more about signs of prostate cancer.

Treatment for prostate cancer

Treatment options for prostate cancer are based on your specific diagnosis. Standard treatments for prostate cancer include watchful waiting or active surveillance, surgery, radiation therapy, hormone therapy, chemotherapy, targeted therapy, and immunotherapy, among others. There are also new treatments for prostate cancer that are being tested in clinical trials. Learn about prostate cancer treatment.  

Talk with your doctor about prostate health

Older man and woman have a conversation with their doctor while seated at a table.

Your doctor will talk with you about diagnostic tests and treatment options for your prostate condition or disease.

Questions to ask your primary care doctor or urologist

  • What prostate condition or disease do I have?
  • What type of treatment do you recommend for my prostate problem?
  • What are possible side effects that men have from this procedure or treatment? 

Prostate-Specific Antigen (PSA) Test

Prostate-Specific Antigen (PSA) Test

What is the PSA test?

Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. Both prostate cancer and several benign conditions (particularly benign prostatic hyperplasia, or BPH, and prostatitis) can cause PSA levels in the blood to rise. 

The PSA test measures the level of PSA in the blood. This test is used in several different ways:

  • to monitor the progression of prostate cancer in men who have already been diagnosed with the disease
  • to follow up on prostate symptoms, such as painful or frequent urination, blood in urine or semen, and pelvic and/or back pain
  • to screen for prostate cancer in men who do not have symptoms of the disease

The PSA test is not recommended for routine prostate cancer screening in the general population. It was used for this purpose for several decades, beginning in the late 1980s. But by around 2008, as more was learned about both the benefits and harms of prostate cancer screening, many professional medical organizations began to caution against routine population screening with the PSA test. Most organizations now recommend that individuals who are considering PSA screening first discuss the risks and benefits with their doctors before making a decision. 

Some organizations do recommend that men who are at higher risk of prostate cancer have routine PSA testing, beginning at age 40 or 45. Those at higher risk include Black men, men with inherited variants in BRCA2 (and to a lesser extent, in BRCA1), and men whose father or brother had prostate cancer.

The current recommendation of the United States Preventive Serves Task Force (USPSTF), which applies both to the general population and to those at increased risk due to race/ethnicity or family history, is as follows:

  • For individuals aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one. Before making the decision, a person should discuss the potential benefits and harms of screening with their clinician and consider these in the context of their own values and preferences.
  • PSA-based screening for prostate cancer is not recommended for individuals 70 years and older. 

Currently, Medicare provides coverage for an annual PSA test for all Medicare-eligible individuals over 50. Many private insurers cover PSA screening as well.

What is a normal PSA test result?

There is no single threshold that distinguishes a normal versus an abnormal PSA result. This is in part because there is no specific PSA level that means that someone has prostate cancer. However, the higher someone’s PSA level, the likelier it is that prostate cancer is present.

In general, a PSA level above 4.0 ng/mL is considered abnormal and may result in a recommendation for prostate biopsy. However, because PSA levels increase with age, some doctors apply a higher cutoff (such as 5 ng/ml) for older men and a lower cutoff ( such as 2.5 ng/mL) for younger men (1).

In addition, a lower cutoff for abnormal is used in men taking certain drugs, including finasteride and dutasteride, which are used to treat BPH. These drugs lower the PSA level.

Various factors can increase someone’s PSA level temporarily. An infection or inflammation of the prostate or having had a recent prostate biopsy can cause PSA levels to be raised for a month or two. Vigorous exercise (such as cycling) and ejaculation can also increase the PSA level transiently. People are generally recommended to wait until any conditions that can change PSA level resolve before they have testing and to avoid activities that may raise the PSA level for 2 days before testing.

What is done if a screening test shows an elevated PSA level?

If someone who has no symptoms of prostate cancer chooses to undergo prostate cancer screening and is found to have an abnormal PSA level, the doctor may recommend another PSA test in 6 to 8 weeks to confirm the original finding. If the PSA level is still elevated, the doctor may recommend continued observation with repeat PSA tests along with digital rectal exams (DREs) to watch for any changes over time.

If the PSA level continues to rise—especially if it rises quickly—or if a lump is detected during a DRE, the doctor may recommend additional tests. These may include additional blood- or urine-based tests, or imaging tests, such as magnetic resonance imaging (MRI) or high-resolution micro-ultrasound.

Alternatively, the doctor may recommend a prostate biopsy without further testing. During this procedure, multiple samples of prostate tissue are collected by inserting hollow needles into the prostate and then withdrawing them. The biopsy needle may be inserted through the wall of the rectum (transrectal biopsy) or through the perineum (transperineal biopsy). A pathologist then examines the collected tissue under a microscope. Although both biopsy techniques are guided by ultrasound imaging so the doctor can view the prostate during the biopsy procedure, ultrasound cannot be used alone to diagnose prostate cancer. An MRI-guided biopsy may be performed for patients with suspicious areas seen on MRI.

What are some of the potential benefits and harms of the PSA test for prostate cancer screening?

The potential benefit of the PSA test for prostate cancer screening is that it may help detect prostate cancer earlier, before it spreads and when it may be easier to treat, possibly reducing someone’s risk of dying from prostate cancer. 

A systematic review and meta-analysis of all randomized controlled trials comparing PSA screening with usual care in men without a diagnosis of prostate cancer concluded that PSA screening for prostate cancer leads to a small reduction in prostate cancer mortality over 10 years (2).

However, this potential benefit needs to be balanced against several potential harms:

  • Some cancers detected through PSA screening grow so slowly that they would never cause symptoms or become life threatening. However, treating them can cause harms. Detecting tumors that would not have caused problems during someone’s lifetime is called “overdiagnosis,” and treating them is called “overtreatment.”

    Overtreatment exposes a person unnecessarily to potential complications. These include urinary, bowel, and sexual side effects, such as leaking of urine following surgery; increased frequency and urgency of urination following radiation; loose stools or, less commonly, rectal bleeding, following radiation; and loss of erections or decreased erections, following both surgery and radiation.
     

  • Detecting prostate cancer earlier does not always result in cure. While the PSA test can help detect small tumors, some of these tumors, regardless of size, may have already spread beyond the prostate before being detected and may not be curable.
     
  • The PSA test may give false-positive results. A false-positive test result occurs when the PSA level is elevated but no cancer is present. A false-positive test result may create anxiety and lead to additional medical procedures, such as a prostate biopsy, that can be harmful. Possible side effects of biopsies include serious infections, pain, and bleeding.

    False-positive test results are common with PSA screening. About 6%–7% of men have a false-positive PSA test on any given screening round, and only about 25% of men who have a biopsy due to an elevated PSA level are found to have prostate cancer (3). 

The United States Preventive Services Task Force has estimated that, for every 1,000 men ages 55 to 69 years who are screened for 13 years (4):

  • About 1.3 deaths from prostate cancer would be avoided (or 1 death avoided per 769 men screened). Subsequent trial data showed that up to 2 deaths from prostate cancer would be avoided per every 1,000 men screened (or 1 death avoided in 570 men screened) (5).
  • 3 men would avoid developing metastatic cancer.
  • 5 men would die from prostate cancer despite having screening, diagnosis, and treatment.
  • 240 men would have a positive PSA test result, many of whom would have a biopsy that shows that the result was a false-positive; some men who had a biopsy would experience at least moderately bothersome symptoms (pain, bleeding, or infection) from the procedure (and 2 would be hospitalized).
  • 100 men would be diagnosed with prostate cancer. Of those, 80 would be treated (either immediately or after a period of active surveillance) with surgery or radiation. Many of these men would have a serious complication from treatment, with 50 experiencing sexual dysfunction and 15 experiencing urinary incontinence.
  • 200 men would die of causes other than prostate cancer.

How is the PSA test used in people who have been treated for prostate cancer?

The PSA test is used to monitor people after surgery or radiation therapy for prostate cancer to see if their cancer has recurred (come back). If a person’s PSA level begins to rise after prostate cancer treatment, it may be the first sign of a recurrence. Such a “biochemical relapse” typically appears months or years before the recurrence causes symptoms.

However, a single elevated PSA measurement in someone who has a history of prostate cancer does not always mean that the cancer has come back. Someone who has been treated for prostate cancer should discuss an elevated PSA level with their doctor. The doctor may recommend repeating the PSA test or performing other tests to check for evidence of a recurrence. The doctor may look for a trend of rising PSA level over time rather than a single elevated PSA level.

A rising trend in PSA level over time in combination with other findings, such as an abnormal result on imaging tests, may lead the doctor to recommend further cancer treatment.

How are researchers trying to improve the PSA test?

Scientists are investigating ways to improve the PSA test and to identify other potential biomarkers and imaging tests to help doctors better distinguish cancerous from benign conditions and slow-growing cancers from fast-growing, potentially lethal cancers. None of these tests has yet been proven to decrease the risk of death from prostate cancer. Some of the methods being studied include:

Blood-based tests. Tests that measure different characteristics of PSA in the blood may help

  • determine whether a prostate biopsy is needed (Prostate Health Index)
  • determine the risk of a high-grade prostate cancer requiring a biopsy (IsoPSA [6])
  • assess the risk of aggressive prostate cancer in someone with an abnormal prostate screening result (4Kscore test)

Urine-based tests. Tests that measure biomarkers in the urine may help

  • prevent an unnecessary biopsy among people with an elevated blood PSA (PCA3 mRNA and the TMPRSS2-ERG gene fusion in combination with PSA and the MPS2 test [7])
  • screen for prostate cancer (exosomal PCA3, SPDEF, and ERG RNA [ExoDx Prostate IntelliScore]; HOXC6 and DLX1 mRNA after an abnormal PSA and/or DRE [SelectMDx]; and small non-coding RNAs [Sentinel PCa Test])

Imaging tests. Tests that integrate magnetic resonance imaging (MRI) into PSA and biomarker screening are being studied to assess the risk of prostate cancer before a biopsy (8).

Prostate Cancer Screening (PDQ®)–Patient Version

Prostate Cancer Screening (PDQ®)–Patient Version

What Is Screening?

Go to Health Professional Version

Screening is looking for cancer before a person has any symptoms. This can help find cancer at an early stage. When abnormal tissue or cancer is found early, it may be easier to treat. By the time symptoms appear, cancer may have begun to spread.

Scientists are trying to better understand which people are more likely to get certain types of cancer. They also study the things we do and the things around us to see if they cause cancer. This information helps doctors recommend who should be screened for cancer, which screening tests should be used, and how often the tests should be done.

It is important to remember that your doctor does not necessarily think you have cancer if he or she suggests a screening test. Screening tests are given when you have no cancer symptoms. Screening tests may be repeated on a regular basis.

If a screening test result is abnormal, you may need to have more tests done to find out if you have cancer. These are called diagnostic tests.

General Information About Prostate Cancer

Key Points

  • Prostate cancer is a disease in which malignant (cancer) cells form in the tissues of the prostate.
  • Prostate cancer is the most common nonskin cancer among men in the United States.
  • Different factors increase or decrease the risk of developing prostate cancer.

Prostate cancer is a disease in which malignant (cancer) cells form in the tissues of the prostate.

The prostate is a gland in the male reproductive system. It lies just below the bladder (the organ that collects and empties urine) and in front of the rectum (the lower part of the intestine). It is about the size of a walnut and surrounds part of the urethra (the tube that empties urine from the bladder). The prostate gland makes fluid that is part of the semen.

EnlargeDrawing of the male reproductive system and urinary system anatomy showing the front and side views of the ureters, bladder, prostate gland, vas deferens, urethra, penis, and testicles. A side view of the seminal vesicle and ejaculatory duct is also shown. The drawing also shows front and side views of the rectum and lymph nodes in the pelvis.
Anatomy of the male reproductive and urinary systems showing the ureters, bladder, prostate gland, urethra, penis, testicles, and other organs.

As men age, the prostate may get bigger. A bigger prostate may block the flow of urine from the bladder and cause problems with sexual function. This condition is called benign prostatic hyperplasia (BPH). BPH is not cancer, but surgery may be needed to correct it. The symptoms of BPH or of other problems in the prostate may be similar to symptoms of prostate cancer.

EnlargeTwo-panel drawing shows normal male reproductive and urinary anatomy and benign prostatic hyperplasia (BPH). Panel on the left shows the normal prostate and flow of urine from the bladder through the urethra. Panel on the right shows an enlarged prostate pressing on the bladder and urethra, blocking the flow of urine.
Normal prostate and benign prostatic hyperplasia (BPH). A normal prostate does not block the flow of urine from the bladder. An enlarged prostate presses on the bladder and urethra and blocks the flow of urine.

Other PDQ summaries containing information related to prostate cancer include:

Prostate cancer is the most common nonskin cancer among men in the United States.

Prostate cancer is most common in older men. In the United States, about one out of every eight men will be diagnosed with prostate cancer. Most men diagnosed with this disease do not die from it. Prostate cancer causes more deaths in men than any other cancer except lung cancer. Prostate cancer occurs more often in Black men than in White men. Black men with prostate cancer are more likely to die from the disease than White men with prostate cancer.

Different factors increase or decrease the risk of developing prostate cancer.

Anything that increases your chance of getting a disease is called a risk factor. Anything that decreases your chance of getting a disease is called a protective factor.

To learn more about risk factors and protective factors for prostate cancer, visit Prostate Cancer Prevention.

Prostate Cancer Screening

Key Points

  • Tests are used to screen for different types of cancer when a person does not have symptoms.
  • There is no standard or routine screening test for prostate cancer.
    • Digital rectal exam
    • Prostate-specific antigen test
  • A prostate cancer gene 3 (PCA3) RNA test may be used for certain patients.
  • Screening tests for prostate cancer are being studied in clinical trials.

Tests are used to screen for different types of cancer when a person does not have symptoms.

Scientists study screening tests to find those with the fewest harms and most benefits. Cancer screening trials also are meant to show whether early detection (finding cancer before it causes symptoms) helps a person live longer or decreases a person’s chance of dying from the disease. For some types of cancer, the chance of recovery is better if the disease is found and treated at an early stage.

There is no standard or routine screening test for prostate cancer.

Although there are no standard or routine screening tests for prostate cancer, the following tests are being used or studied to screen for it:

Digital rectal exam

Digital rectal exam (DRE) is an exam of the rectum. The doctor or nurse inserts a lubricated, gloved finger into the lower part of the rectum to feel the prostate for lumps or anything else that seems unusual, such as an enlarged prostate.

EnlargeDigital rectal exam; drawing shows a side view of the male reproductive anatomy and the urinary anatomy, including the prostate, rectum, and bladder. Also shown is a gloved, lubricated finger inserted into the rectum to feel the rectum, anus, and prostate.
Digital rectal exam (DRE). The doctor inserts a gloved, lubricated finger into the rectum and feels the rectum, anus, and prostate (in males) to check for anything abnormal.

Prostate-specific antigen test

A prostate-specific antigen (PSA) test is a test that measures the level of PSA in the blood. PSA is a substance made mostly by the prostate that may be found in an increased amount in the blood of men who have prostate cancer. The level of PSA may also be high in men who have an infection or inflammation of the prostate or benign prostatic hyperplasia (BPH; an enlarged, but noncancerous, prostate).

A PSA test or a DRE may be able to detect prostate cancer at an early stage, but it is not clear whether early detection and treatment decrease the risk of dying from prostate cancer.

Studies are being done to find ways to make PSA testing more accurate for early cancer detection.

A prostate cancer gene 3 (PCA3) RNA test may be used for certain patients.

If a man had a high PSA level and a biopsy of the prostate did not show cancer and the PSA level remains high after the biopsy, a PCA3 RNA test may be done. This test measures the amount of PCA3 RNA in the urine after a DRE. If the PCA3 RNA level is higher than normal, another prostate biopsy may be needed to help diagnose prostate cancer.

Screening tests for prostate cancer are being studied in clinical trials.

Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Risks of Prostate Cancer Screening

Key Points

  • Screening tests have risks.
  • The risks of prostate cancer screening include:
    • Finding prostate cancer that may never cause symptoms or become life threatening.
    • Complications from a follow-up biopsy can occur.
    • False-negative test results can occur.
    • False-positive test results can occur.

Screening tests have risks.

Decisions about screening tests can be difficult. Not all screening tests are helpful, and most have risks. Before having any screening test, you may want to discuss the test with your doctor. It is important to know the risks of the test and whether it has been proven to reduce the risk of dying from cancer.

The risks of prostate cancer screening include:

Finding prostate cancer that may never cause symptoms or become life threatening.

Screening may not improve your health or help you live longer if you have cancer that has already spread to the area outside of the prostate or to other places in your body.

Some prostate cancers never cause symptoms or become life-threatening, but if found by a screening test, the cancer may be treated. Finding these cancers is called overdiagnosis. It is not known if treatment of these cancers would help you live longer than if no treatment were given.

Treatments for prostate cancer, such as radical prostatectomy and radiation therapy, may have long-term side effects in many men. The most common side effects are erectile dysfunction and urinary incontinence.

Some studies of patients with newly diagnosed prostate cancer showed these patients had a higher risk of death from cardiovascular (heart and blood vessel) disease or suicide. The risk was greatest in the first weeks or months after diagnosis.

Complications from a follow-up biopsy can occur.

If a PSA test is higher than normal, a biopsy of the prostate may be done. Complications from a biopsy of the prostate may include fever, pain, blood in the urine or semen, and urinary tract infection. Even if a biopsy shows that a patient does not have prostate cancer, he may worry more about developing prostate cancer in the future.

Magnetic resonance imaging (MRI)−guided biopsy is being studied in the diagnosis of prostate cancer, either in place of, or in addition to, standard prostate needle biopsy.

False-negative test results can occur.

Screening test results may appear to be normal even though prostate cancer is present. A man who receives a false-negative test result (one that shows there is no cancer when there really is) may delay seeking medical care even if he has symptoms.

False-positive test results can occur.

Screening test results may appear to be abnormal even though no cancer is present. A false-positive test result (one that shows there is cancer when there really isn’t) can cause anxiety and is usually followed by more tests and procedures (such as a biopsy), which also have risks.

Your doctor can advise you about your risk for prostate cancer and your need for screening tests.

About This PDQ Summary

About PDQ

Physician Data Query (PDQ) is the National Cancer Institute’s (NCI’s) comprehensive cancer information database. The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come in two versions. The health professional versions have detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions have cancer information that is accurate and up to date and most versions are also available in Spanish.

PDQ is a service of the NCI. The NCI is part of the National Institutes of Health (NIH). NIH is the federal government’s center of biomedical research. The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH.

Purpose of This Summary

This PDQ cancer information summary has current information about prostate cancer screening. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

Reviewers and Updates

Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary (“Updated”) is the date of the most recent change.

The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Screening and Prevention Editorial Board.

Clinical Trial Information

A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become “standard.” Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Clinical trials can be found online at NCI’s website. For more information, call the Cancer Information Service (CIS), NCI’s contact center, at 1-800-4-CANCER (1-800-422-6237).

Permission to Use This Summary

PDQ is a registered trademark. The content of PDQ documents can be used freely as text. It cannot be identified as an NCI PDQ cancer information summary unless the whole summary is shown and it is updated regularly. However, a user would be allowed to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks in the following way: [include excerpt from the summary].”

The best way to cite this PDQ summary is:

PDQ® Screening and Prevention Editorial Board. PDQ Prostate Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: /types/prostate/patient/prostate-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389306]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use in the PDQ summaries only. If you want to use an image from a PDQ summary and you are not using the whole summary, you must get permission from the owner. It cannot be given by the National Cancer Institute. Information about using the images in this summary, along with many other images related to cancer can be found in Visuals Online. Visuals Online is a collection of more than 3,000 scientific images.

Disclaimer

The information in these summaries should not be used to make decisions about insurance reimbursement. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s E-mail Us.

Prostate Cancer Prevention (PDQ®)–Patient Version

Prostate Cancer Prevention (PDQ®)–Patient Version

What is prevention?

Go to Health Professional Version

Cancer prevention is action taken to lower the chance of getting cancer. By preventing cancer, the number of new cases of cancer in a group or population is lowered. Hopefully, this will lower the number of deaths caused by cancer.

To prevent new cancers from starting, scientists look at risk factors and protective factors. Anything that increases your chance of developing cancer is called a cancer risk factor; anything that decreases your chance of developing cancer is called a cancer protective factor.

Some risk factors for cancer can be avoided, but many cannot. For example, both smoking and inheriting certain genes are risk factors for some types of cancer, but only smoking can be avoided. Regular exercise and a healthy diet may be protective factors for some types of cancer. Avoiding risk factors and increasing protective factors may lower your risk but it does not mean that you will not get cancer.

Different ways to prevent cancer are being studied.

General Information About Prostate Cancer

Key Points

  • Prostate cancer is a disease in which malignant (cancer) cells form in the tissues of the prostate.
  • Prostate cancer is the second most common cancer among men in the United States.

Prostate cancer is a disease in which malignant (cancer) cells form in the tissues of the prostate.

The prostate is a gland in the male reproductive system. The prostate is just below the bladder (the organ that collects and empties urine) and in front of the rectum (the lower part of the intestine). It is about the size of a walnut and surrounds part of the urethra (the tube that empties urine from the bladder). The prostate gland produces fluid that makes up part of the semen.

EnlargeDrawing of the male reproductive system and urinary system anatomy showing the front and side views of the ureters, bladder, prostate gland, vas deferens, urethra, penis, and testicles. A side view of the seminal vesicle and ejaculatory duct is also shown. The drawing also shows front and side views of the rectum and lymph nodes in the pelvis.
Anatomy of the male reproductive and urinary systems showing the ureters, bladder, prostate gland, urethra, penis, testicles, and other organs.

As men age, the prostate may get bigger. A bigger prostate may block the flow of urine from the bladder and cause problems with sexual function. This condition is called benign prostatic hyperplasia (BPH). BPH is not cancer, but surgery may be needed to correct it. The symptoms of BPH or of other problems in the prostate may be like symptoms of prostate cancer.

EnlargeTwo-panel drawing shows normal male reproductive and urinary anatomy and benign prostatic hyperplasia (BPH). Panel on the left shows the normal prostate and flow of urine from the bladder through the urethra. Panel on the right shows an enlarged prostate pressing on the bladder and urethra, blocking the flow of urine.
Normal prostate and benign prostatic hyperplasia (BPH). A normal prostate does not block the flow of urine from the bladder. An enlarged prostate presses on the bladder and urethra and blocks the flow of urine.

Prostate cancer is the second most common cancer among men in the United States.

Prostate cancer is most common in older men. In the United States, about one out of every eight men will be diagnosed with prostate cancer. Most men diagnosed with prostate cancer do not die of it.

See the following PDQ summaries for more information about prostate cancer:

Prostate Cancer Prevention

Key Points

  • Avoiding risk factors and increasing protective factors may help prevent cancer.
  • The following risk factors may increase the risk of prostate cancer:
    • Age
    • Family history of prostate cancer
    • Race
    • Hormones
    • Vitamin E
    • Folic acid
    • Dairy and calcium
  • The following protective factors may decrease the risk of prostate cancer:
    • Folate
    • Finasteride and dutasteride
  • The following have been proven not to affect the risk of prostate cancer, or their effects on prostate cancer risk are not known:
    • Selenium and vitamin E
    • Diet
    • Multivitamins
    • Lycopene
  • Cancer prevention clinical trials are used to study ways to prevent cancer.
  • New ways to prevent prostate cancer are being studied in clinical trials.

Avoiding risk factors and increasing protective factors may help prevent cancer.

Avoiding cancer risk factors may help prevent certain cancers. Risk factors include smoking, having overweight, and not getting enough exercise. Increasing protective factors such as quitting smoking and exercising may also help prevent some cancers. Talk to your doctor or other health care professional about how you might lower your risk of cancer.

The following risk factors may increase the risk of prostate cancer:

Age

Prostate cancer is rare in men younger than 50 years of age. The chance of developing prostate cancer increases as men get older.

Family history of prostate cancer

A man whose father, brother, or son has had prostate cancer has a higher-than-average risk of prostate cancer.

Race

Prostate cancer occurs more often in African American men than in White men. African American men with prostate cancer are more likely to die from the disease than White men with prostate cancer.

Hormones

The prostate needs male hormones to work the way it should. The main male sex hormone is testosterone. Testosterone helps the body develop and maintain male sex characteristics.

Testosterone is changed into dihydrotestosterone (DHT) by an enzyme in the body. DHT is important for normal prostate growth but can also cause the prostate to get bigger and may play a part in the development of prostate cancer.

Vitamin E

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) found that vitamin E taken alone increased the risk of prostate cancer. The risk continued even after the men stopped taking vitamin E.

Folic acid

Folate is a kind of vitamin B that occurs naturally in some foods, such as green vegetables, beans, and orange juice. Folic acid is a man-made form of folate that is found in vitamin supplements and fortified foods, such as whole-grain breads and cereals. A 10-year study showed that the risk of prostate cancer was increased in men who took 1 milligram (mg) supplements of folic acid. However, the risk of prostate cancer was lower in men who had enough folate in their diets.

Dairy and calcium

A diet high in dairy foods and calcium may cause a small increase in the risk of prostate cancer.

The following protective factors may decrease the risk of prostate cancer:

Folate

Folate is a kind of vitamin B that occurs naturally in some foods, such as green vegetables, beans, and orange juice. Folic acid is a man-made form of folate that is found in vitamin supplements and fortified foods, such as whole-grain breads and cereals. A 10-year study showed that the risk of prostate cancer was lower in men who had enough folate in their diets. However, the risk of prostate cancer was increased in men who took 1 milligram (mg) supplements of folic acid.

Finasteride and dutasteride

Finasteride and dutasteride are drugs used to lower the amount of male sex hormones made by the body. These drugs block the enzyme that changes testosterone into dihydrotestosterone (DHT). Higher than normal levels of DHT may play a part in developing prostate cancer. Taking finasteride or dutasteride has been shown to lower the risk for prostate cancer, but it is not known if these drugs lower the risk of death from prostate cancer.

The Prostate Cancer Prevention Trial (PCPT) studied whether the drug finasteride can prevent prostate cancer in healthy men 55 years of age and older. This prevention study showed there were fewer prostate cancers in the group of men that took finasteride compared with the group of men that did not. The number of deaths from prostate cancer was the same in both groups. Men who took finasteride reported more side effects compared with the group of men that did not, including erectile dysfunction, loss of desire for sex, and enlarged breasts. In the PCPT, the men who took finasteride who did have prostate cancer had more aggressive tumors, but a follow-up analysis of the PCPT found that these men did not have more aggressive tumors.

The Reduction by Dutasteride of Prostate Cancer Events Trial (REDUCE) studied whether the drug dutasteride can prevent prostate cancer in men aged 50 to 75 years at higher risk for the disease. This prevention study showed there were fewer prostate cancers in the group of men who took dutasteride compared with the group of men that did not. The number of less aggressive prostate cancers was lower, but the number of more aggressive prostate cancers was not. Men who took dutasteride reported more side effects than men who did not, including erectile dysfunction, loss of desire for sex, less semen, and enlarged breasts.

The following have been proven not to affect the risk of prostate cancer, or their effects on prostate cancer risk are not known:

Selenium and vitamin E

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) studied whether taking vitamin E and selenium (a mineral) will prevent prostate cancer. The selenium and vitamin E were taken separately or together by healthy men 55 years of age and older (50 years of age and older for African American men). The study showed that taking selenium alone or selenium and vitamin E together did not decrease the risk of prostate cancer.

Diet

It is not known if decreasing fat or increasing fruits and vegetables in the diet helps decrease the risk of prostate cancer or death from prostate cancer. In the PCPT trial, certain fatty acids increased the risk of high-grade prostate cancer while others decreased the risk of high-grade prostate cancer.

Multivitamins

Regular use of multivitamins has not been proven to increase the risk of early or localized prostate cancer. However, a large study showed an increased risk of advanced prostate cancer among men who took multivitamins more than seven times a week.

Lycopene

Some studies have shown that a diet high in lycopene may be linked to a decreased risk of prostate cancer, but other studies have not. It has not been proven that taking lycopene supplements decreases the risk of prostate cancer.

Cancer prevention clinical trials are used to study ways to prevent cancer.

Cancer prevention clinical trials are used to study ways to lower the risk of developing certain types of cancer. Some cancer prevention trials are conducted with healthy people who have not had cancer but who have an increased risk for cancer. Other prevention trials are conducted with people who have had cancer and are trying to prevent another cancer of the same type or to lower their chance of developing a new type of cancer. Other trials are done with healthy volunteers who are not known to have any risk factors for cancer.

The purpose of some cancer prevention clinical trials is to find out whether actions people take can prevent cancer. These may include eating fruits and vegetables, exercising, quitting smoking, or taking certain medicines, vitamins, minerals, or food supplements.

New ways to prevent prostate cancer are being studied in clinical trials.

Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

About This PDQ Summary

About PDQ

Physician Data Query (PDQ) is the National Cancer Institute’s (NCI’s) comprehensive cancer information database. The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come in two versions. The health professional versions have detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions have cancer information that is accurate and up to date and most versions are also available in Spanish.

PDQ is a service of the NCI. The NCI is part of the National Institutes of Health (NIH). NIH is the federal government’s center of biomedical research. The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH.

Purpose of This Summary

This PDQ cancer information summary has current information about prostate cancer prevention. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

Reviewers and Updates

Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary (“Updated”) is the date of the most recent change.

The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Screening and Prevention Editorial Board.

Clinical Trial Information

A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become “standard.” Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Clinical trials can be found online at NCI’s website. For more information, call the Cancer Information Service (CIS), NCI’s contact center, at 1-800-4-CANCER (1-800-422-6237).

Permission to Use This Summary

PDQ is a registered trademark. The content of PDQ documents can be used freely as text. It cannot be identified as an NCI PDQ cancer information summary unless the whole summary is shown and it is updated regularly. However, a user would be allowed to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks in the following way: [include excerpt from the summary].”

The best way to cite this PDQ summary is:

PDQ® Screening and Prevention Editorial Board. PDQ Prostate Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: /types/prostate/patient/prostate-prevention-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389260]

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Prostate Cancer Prevention (PDQ®)–Health Professional Version

Prostate Cancer Prevention (PDQ®)–Health Professional Version

Overview

Go to Patient Version

Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.

Other PDQ summaries on Prostate Cancer Screening; Prostate Cancer Treatment; and Levels of Evidence for Cancer Screening and Prevention Studies are also available.

Benefits From Finasteride and Dutasteride Chemoprevention

Chemoprevention with finasteride and dutasteride reduces the incidence of prostate cancer, but the evidence is inadequate to determine whether chemoprevention with finasteride or dutasteride reduces mortality from prostate cancer.

Magnitude of Effect: In the Prostate Cancer Prevention Trial (PCPT), absolute reduction in incidence for more than 7 years with finasteride as compared with placebo was 6% (18.4% with finasteride and 24.4% with placebo); relative risk reduction (RRR) for incidence was 24.8% (95% confidence interval [CI], 18.6%–30.6%). With long-term follow-up (median, 18.4 years), prostate cancer mortality was not statistically different between men in the placebo and finasteride groups of PCPT (hazard ratio [HR], finasteride vs. placebo, 0.75; 95% CI, 0.50–1.12). Long-term follow-up (median, 16 years) of PCPT participants found that with 7 years of finasteride therapy, there was a 21.1% relative reduction in risk of prostate cancer.[1]

In the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) randomized trial of dutasteride versus placebo, using the restricted crude rate, the absolute risk reduction was 5.1% at 4 years, and the RRR was 22.8% (95% CI, 15.2%–29.8%; P < .001). There was no difference in prostate cancer or overall mortality, although the number of deaths was small and none were due to prostate cancer. The reduction in prostate cancer incidence occurred primarily in Gleason score 5 to 6 cancers.[2] That the reduction in incidence was primarily in less aggressive cancers (i.e., Gleason score 5–6) and not in more aggressive cancers (i.e., Gleason score 7–10) raises the question of whether this reduction in incidence would lead to any reduction in mortality. This question is presently unanswered.

  • Study Design: Two randomized controlled trials; one for finasteride and one for dutasteride.
  • Internal Validity: Good for the outcome of incidence, poor for the outcome of mortality.
  • Consistency: Good.
  • External Validity: The studies focused on different populations. The finasteride trial enrolled men with a prostate-specific antigen (PSA) of less than 3 ng/mL, constituting the majority of U.S. men, but those with a lower risk of cancer. In the dutasteride trial, men were at somewhat higher risk, with a PSA of 2.5 to 10.0 ng/mL and a prior negative biopsy. As such, results are generalizable primarily to these respective populations.

Harms From Finasteride and Dutasteride Chemoprevention

Finasteride

Men in the finasteride group had statistically significantly more erectile dysfunction, loss of libido, and gynecomastia than men in the placebo group. Men in the finasteride group had a statistically significant higher incidence of high-grade (Gleason score 7–10) cancers during the study than did men in the placebo group (relative risk, 1.27; 95% CI, 1.07–1.50).[3] Subsequent studies showed that diagnostic tests (PSA, prostate digital rectal exam, and prostate biopsy) had improved performance for detection of cancer and of high-grade cancer in men who received finasteride.[4–6] Long-term follow-up in the finasteride trial (PCPT) found no increased risk of prostate cancer mortality (HR, finasteride vs. placebo, 0.75; 95% CI, 0.50–1.12).

Magnitude of Effect: Statistically significant increases in the following outcomes were observed in the finasteride group (a greater fraction of men in the finasteride group [36.8%] temporarily discontinued treatment at some time during the study for reasons other than death or a diagnosis of prostate cancer than in the placebo group [28.9%]):

  • Percentage in finasteride group versus percentage in placebo group:
    • Reduced volume of ejaculate (60.4% vs. 47.3%).
    • Erectile dysfunction (67.4% vs. 61.5%).
    • Loss of libido (65.4% vs. 59.6%).
    • Gynecomastia (4.5% vs. 2.8%).
  • Study Design: Two randomized controlled trials; one for finasteride and one for dutasteride.
  • Internal Validity: Good: The finasteride trial used two subject-completed sexual functioning instruments administered at enrollment, randomization, 6 months, and annually over the 7-year study. The dutasteride trial administered a sexual functioning instrument after completion of placebo run-in and annually thereafter.
  • Consistency: Good (evidence other than the randomized controlled trial supports these effects).
  • External Validity: As above, the studies evaluated two different populations: PSA less than or equal to 3 ng/mL in the finasteride trial and PSA of 2.5 to 10.0 ng/mL with a prior negative biopsy in the REDUCE trial. The results are most generalizable to these two populations.

Dutasteride

Overall, 4.3% of men in the dutasteride group compared with 2% of men in the placebo group discontinued the trial because of drug-related adverse events (P < .001). Men in the dutasteride group had a higher incidence of decreased libido, loss of libido, decreased semen volume, erectile dysfunction, and gynecomastia than men in the placebo group.[2]

Magnitude of Effect: Increases in the following outcomes were observed in the dutasteride group:

  • Percentage in dutasteride group versus percentage in placebo group:
    • Decreased libido (3.3% vs. 1.6%).
    • Loss of libido (1.9% vs. 1.3%).
    • Decreased semen volume (1.4% vs. 0.2%).
    • Erectile dysfunction (9.0% vs. 5.7%).
    • Gynecomastia (1.9% vs. 1.0%).

U.S. Food and Drug Administration (FDA) Review of Finasteride and Dutasteride

The Oncology Drugs Advisory Committee of the FDA examined both finasteride and dutasteride in 2010. Neither agent was recommended for use for chemoprevention of prostate cancer.

Other Prevention Interventions

The Selenium and Vitamin E Cancer Prevention Trial (SELECT [NCT00006392]) was a large randomized placebo-controlled trial of vitamin E and selenium. It showed no reduction in prostate cancer period prevalence, but an increased risk of prostate cancer with vitamin E alone.[7]

Magnitude of Effect: Compared with the placebo group in which 529 men developed prostate cancer, there was a statistically significant increase in prostate cancer in the vitamin E group (620 cases) but not in the selenium plus vitamin E group (555 cases) or in the selenium group (575 cases). The magnitude of increase in prostate cancer risk with vitamin E alone was 17%.

  • Study Design for Vitamin E and Selenium: Randomized, placebo-controlled trial of selenium (200 µg/d from L-selenomethionine), vitamin E (400 IU/d of all-rac-[alpha]-tocopheryl acetate), or both.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.
References
  1. Unger JM, Hershman DL, Till C, et al.: Using Medicare Claims to Examine Long-term Prostate Cancer Risk of Finasteride in the Prostate Cancer Prevention Trial. J Natl Cancer Inst 110 (11): 1208-1215, 2018. [PUBMED Abstract]
  2. Andriole GL, Bostwick DG, Brawley OW, et al.: Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362 (13): 1192-202, 2010. [PUBMED Abstract]
  3. Thompson IM, Goodman PJ, Tangen CM, et al.: The influence of finasteride on the development of prostate cancer. N Engl J Med 349 (3): 215-24, 2003. [PUBMED Abstract]
  4. Thompson IM, Chi C, Ankerst DP, et al.: Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J Natl Cancer Inst 98 (16): 1128-33, 2006. [PUBMED Abstract]
  5. Thompson IM, Tangen CM, Goodman PJ, et al.: Finasteride improves the sensitivity of digital rectal examination for prostate cancer detection. J Urol 177 (5): 1749-52, 2007. [PUBMED Abstract]
  6. Lucia MS, Epstein JI, Goodman PJ, et al.: Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. J Natl Cancer Inst 99 (18): 1375-83, 2007. [PUBMED Abstract]
  7. Klein EA, Thompson IM, Tangen CM, et al.: Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306 (14): 1549-56, 2011. [PUBMED Abstract]

Incidence and Mortality of Prostate Cancer

Carcinoma of the prostate is the most common tumor in men in the United States (other than skin cancer), with an estimated 313,780 new cases and 35,770 deaths expected in 2025.[1] A wide range of estimates of the impact of the disease are notable. The disease is histologically evident in as many as 34% of men in their fifth decade and in up to 70% of men aged 80 years and older.[2,3] The lifetime risk of being diagnosed with prostate cancer for U.S. men is 12.8%, while the lifetime risk of dying from prostate cancer is 2.0%.[4] The estimated reduction in life expectancy of men who die of prostate cancer is approximately 9 years.[5]

The extraordinarily high rate of clinically occult prostate cancer in the general population compared with the 20-fold lower likelihood of death from the disease indicates that many of these cancers have low biological risk. Concordant with this observation are the many series of patients with lower-risk (i.e., Gleason grade 6 and some low-volume Gleason grade 7 tumors) prostate cancer managed by surveillance alone with high survival rates at 5 and 10 years of follow-up.[6] Data demonstrate, however, that with longer follow-up, higher-grade cancers are associated with a greater risk of prostate cancer death.[7,8]

Because of marked variability in tumor differentiation from one microscopic field to another, many pathologists will report the range of differentiation among the malignant cells that are present in a biopsy using the Gleason grading system. This grading system includes five histological patterns distinguished by the glandular architecture of the cancer. The architectural patterns are identified and assigned a grade from 1 to 5 with 1 being the most differentiated and 5 being the least differentiated. The sum of the grades of the predominant and next most prevalent will range from 2 (well-differentiated tumors) to 10 (undifferentiated tumors).[9,10] Systematic changes to the histological interpretation of biopsy specimens by anatomical pathologists have occurred during the prostate-specific antigen (PSA) screening era (i.e., since about 1985) in the United States.[11] This phenomenon, sometimes called grade inflation, is the apparent increase in the distribution of high-grade tumors in the population for a period of time but in the absence of a true biological or clinical change. It is possibly the result of an increasing tendency for pathologists to read tumor grade as more aggressive, resulting in a higher preponderance to treat these cancers aggressively.[12] In general, these changes in interpretation have resulted in almost all prostate cancers being graded with Gleason grades of 3, 4, or 5; Gleason grades of 1 or 2 are highly unusual.

Treatment options available for prostate cancer include radical prostatectomy, external-beam radiation therapy, brachytherapy, cryotherapy, focal ablation, androgen deprivation with luteinizing hormone-releasing hormone analogs and/or antiandrogens, intermittent androgen deprivation, cytotoxic agents, and watchful waiting. Of all the means of management, only radical prostatectomy has been tested in a randomized clinical trial to assess survival benefit. In this study, prostatectomy was found to be superior to surveillance in men with localized prostate cancer, diagnosed in an era before widespread PSA screening. There were reduced rates of prostate cancer mortality (relative risk [RR], 0.56; 95% confidence interval [CI], 0.41–0.77) and overall mortality (RR, 0.71; 95% CI, 0.59–0.86).[13] Only 12% of the men had nonpalpable T1x tumors, suggesting that a minority of tumors were detected by PSA screening, whereas the majority were clinically detected. The relative efficacy of radical prostatectomy compared with other forms of treatment has not been adequately addressed.[14] Previous studies that compared radical prostatectomy with radiation therapy and brachytherapy closed because of poor patient accrual. Confounding issues in the treatment of prostate cancer include side effects of treatment, inability to predict the natural history of a given cancer, patient comorbidity that may affect an individual’s likelihood of surviving long enough to be at risk of disease morbidity and mortality, and an increasing body of evidence suggesting that, with careful PSA monitoring following treatment, a substantial fraction of patients may suffer disease recurrence.[15]

Because of considerable uncertainty regarding the efficacy of treatment and the difficulty with selecting patients for whom there is a known risk of disease progression, opinion in the medical community is divided regarding screening for carcinoma of the prostate. While both digital rectal examination and PSA screening have demonstrated reasonable performance characteristics (sensitivity, specificity, and positive predictive value) for the early detection of prostate cancer, conflicting outcomes of randomized trials examining the impact of screening on mortality has led some organizations to recommend for and others to recommend against screening.[16]

The tremendous impact of prostate cancer on the U.S. population and the financial burden of the disease for both patients and society have led to an increased interest in primary disease prevention.

The main treatment modalities for prostate cancer are surgery, radiation, hormonal, and active surveillance. For a detailed discussion, see Prostate Cancer Treatment. The goal of prostate cancer prevention interventions is to reduce the occurrence of prostate cancer, thereby obviating the need for treatment. As the effectiveness of prevention interventions improves, it is expected that the need for treatment will diminish.

References
  1. American Cancer Society: Cancer Facts and Figures 2025. American Cancer Society, 2025. Available online. Last accessed January 16, 2025.
  2. Sakr WA, Haas GP, Cassin BF, et al.: The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol 150 (2 Pt 1): 379-85, 1993. [PUBMED Abstract]
  3. Hølund B: Latent prostatic cancer in a consecutive autopsy series. Scand J Urol Nephrol 14 (1): 29-35, 1980. [PUBMED Abstract]
  4. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
  5. Horm JW, Sondik EJ: Person-years of life lost due to cancer in the United States, 1970 and 1984. Am J Public Health 79 (11): 1490-3, 1989. [PUBMED Abstract]
  6. Cooperberg MR, Carroll PR, Klotz L: Active surveillance for prostate cancer: progress and promise. J Clin Oncol 29 (27): 3669-76, 2011. [PUBMED Abstract]
  7. Lu-Yao GL, Albertsen PC, Moore DF, et al.: Outcomes of localized prostate cancer following conservative management. JAMA 302 (11): 1202-9, 2009. [PUBMED Abstract]
  8. Jones CU, Hunt D, McGowan DG, et al.: Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 365 (2): 107-18, 2011. [PUBMED Abstract]
  9. Gleason DF, Mellinger GT: Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 111 (1): 58-64, 1974. [PUBMED Abstract]
  10. Gleason DF: Histologic grading and clinical staging of prostatic carcinoma. In: Tannenbaum M: Urologic Pathology: The Prostate. Lea and Febiger, 1977, pp 171-197.
  11. Albertsen PC, Hanley JA, Barrows GH, et al.: Prostate cancer and the Will Rogers phenomenon. J Natl Cancer Inst 97 (17): 1248-53, 2005. [PUBMED Abstract]
  12. Thompson IM, Canby-Hagino E, Lucia MS: Stage migration and grade inflation in prostate cancer: Will Rogers meets Garrison Keillor. J Natl Cancer Inst 97 (17): 1236-7, 2005. [PUBMED Abstract]
  13. Bill-Axelson A, Holmberg L, Garmo H, et al.: Radical Prostatectomy or Watchful Waiting in Prostate Cancer – 29-Year Follow-up. N Engl J Med 379 (24): 2319-2329, 2018. [PUBMED Abstract]
  14. Middleton RG, Thompson IM, Austenfeld MS, et al.: Prostate Cancer Clinical Guidelines Panel Summary report on the management of clinically localized prostate cancer. The American Urological Association. J Urol 154 (6): 2144-8, 1995. [PUBMED Abstract]
  15. Moul JW: Prostate specific antigen only progression of prostate cancer. J Urol 163 (6): 1632-42, 2000. [PUBMED Abstract]
  16. Carter HB, Albertsen PC: Re: Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening. J Urol 193 (3): 1063-4; discussion 1064, 2015. [PUBMED Abstract]

Risk Factors for Prostate Cancer Development

Age

Prostate cancer incidence escalates with increasing age. Although it is an unusual disease in men younger than 50 years, incidence rates increase substantially thereafter. Data from the Surveillance, Epidemiology and End Results (SEER) program for 2017 to 2021 showed that incidence rates for prostate cancer were 109.6 per 100,000 for men aged 50 to 54 years, 251.3 per 100,000 for men aged 55 to 59 years, 440.5 per 100,000 for men aged 60 to 64 years, and 693.2 per 100,000 for men aged 65 to 69 years. After age 70 years, incidence rates stabilized or decreased modestly. From 2018 to 2022, mortality rates showed a greater increasing trend with age than did incidence, increasing from 2.8 per 100,000 for men aged 50 to 54 years to 39.1 per 100,000 for men aged 65 to 69 years to 209.7 per 100,000 for men aged 80 to 84 years.[1]

Family History

Approximately 15% of men with a diagnosis of prostate cancer will be found to have a first-degree relative (e.g., brother, father) with prostate cancer, compared with approximately 8% of the U.S. population.[2] Approximately 9% of all prostate cancers may result from heritable susceptibility genes.[3] Several authors have completed segregation analyses, and though a single, rare autosomal gene has been suggested to cause cancer in some of these families, the burden of evidence suggests that the inheritance is considerably more complex.[4–6] Evidence from the Prostate Cancer Prevention Trial (PCPT) and Selenium and Vitamin E Cancer Prevention Trial suggest that physician and patient bias lead to a greater likelihood of prostate biopsy, which contributes significantly to the increased risk of prostate cancer diagnosis in men with a family history of the disease.[7]

Hormones

The development of the prostate is dependent upon the secretion of dihydrotestosterone (DHT) by the fetal testis. Testosterone causes normal virilization of the Wolffian duct structures and internal genitalia and is acted upon by the enzyme 5-alpha-reductase (5AR) to form DHT. DHT has a 4-fold to 50-fold greater affinity for the androgen receptor than testosterone, and it is DHT that leads to normal prostatic development. Children born with abnormal 5AR (due to a change in a single base pair in exon 5 of the normal type II 5AR gene), are born with ambiguous genitalia (variously described as hypospadias with a blind-ending vagina to a small phallus) but masculinize at puberty because of the surge of testosterone production at that time. Clinical, imaging, and histological studies of kindreds born with 5AR deficiency have demonstrated a small, pancake-appearing prostate with an undetectable prostate-specific antigen (PSA) level and no evidence of prostatic epithelium.[8] Long-term follow-up demonstrates that neither benign prostatic hyperplasia (BPH) nor prostate cancer develop.

Other evidence suggesting that the degree of cumulative exposure of the prostate to androgens is related to an increased risk of prostate cancer includes the following:

  1. Neither BPH nor prostate cancer have been reported in men castrated prior to puberty.[9]
  2. Androgen deprivation in almost all forms leads to involution of the prostate, a fall in PSA levels, apoptosis of prostate cancer and epithelial cells, and a clinical response in prostate cancer patients.[10,11]
  3. The results of two large-scale chemoprevention trials using 5AR inhibitors (finasteride and dutasteride) demonstrate that intraprostatic androgens modulate prostate cancer risk. In both studies, reductions in overall prostate cancer risk were identified although with increased risk of high-grade disease.[12,13]

Ecological studies have found a correlation between serum levels of testosterone, especially DHT, and overall risk of prostate cancer among African American, White, and Japanese males.[14–16] However, evidence from prospective studies of the association between serum concentrations of sex hormones, including androgens and estrogens, does not support a direct link.[17] A collaborative analysis of 18 prospective studies, pooling prediagnostic measures on 3,886 men with incident prostate cancer and 6,438 control subjects, found no association between the risk of prostate cancer and serum concentrations of testosterone, calculated-free testosterone, DHT sulfate, androstenedione, androstanediol glucuronide, estradiol, or calculated-free estradiol.[17] A caution for interpreting the data is the unknown degree of correlation between serum levels and prostate tissue level. Androstanediol glucuronide may most closely reflect intraprostatic androgen activity, and this measure was not associated with the risk of prostate cancer. This lack of association affirms that risk stratification cannot be made on serum hormone concentrations.

Race

The risk of developing and dying of prostate cancer is higher among Black men (Hispanic and non-Hispanic), is of intermediate levels among White men (Hispanic and non-Hispanic), and is lowest among native Japanese men.[1,18] Conflicting data have been published regarding the etiology of these outcomes, but some evidence is available that access to health care may play a role in disease outcomes.[19] According to the Surveillance, Epidemiology, and End Results (SEER) Program, incidence of prostate cancer in African American men exceeds those of White men at all ages.[20]

Dietary Fat

An interesting observation is that although the incidence of latent (occult, histologically evident) prostate cancer is similar throughout the world, clinical prostate cancer varies from country to country by as much as 20-fold.[21] Previous ecological studies have demonstrated a direct relationship between a country’s prostate cancer-specific mortality rate and average total calories from fat consumed by the country’s population.[22,23] Studies of immigrants from Japan have demonstrated that native Japanese have the lowest risk of clinical prostate cancer, first-generation Japanese American men have an intermediate risk, and subsequent generations have a risk comparable to the U.S. population.[24,25] Animal models of explanted human prostate cancer have demonstrated decreased tumor growth rates in animals who are fed a low-fat diet.[26,27] Evidence from many case-control studies has shown an association between dietary fat and prostate cancer risk,[28–30] although studies have not uniformly reached this conclusion.[31–33] In a review of published studies of the relationship between dietary fat and prostate cancer risk, among descriptive studies, approximately half found an increased risk with increased dietary fat and half found no association.[34] Among case-control studies, about half of the studies found an increased risk with increasing dietary fat, animal fat, and saturated and monounsaturated fat intake while approximately half found no association. Only in studies of polyunsaturated fat intake were three studies reported of a significant negative association between prostate cancer and fat intake. Fat of animal origin seems to be associated with the highest risk.[19,35] In a series of 384 patients with prostate cancer, the risk of cancer progression to an advanced stage was greater in men with a high fat intake.[36] The announcement in 1996 that cancer mortality rates had fallen in the United States prompted the suggestion that this may be caused by decreases in dietary fat intake during the same time period.[37,38]

Two studies were conducted within the PCPT in which prospective nutritional information was collected and all participants were recommended to undergo biopsy. Findings included that among 9,559 participants, there was no association between any supplement or nutrient (including fat) and risk of prostate cancer overall, but the risk of high-grade cancer was associated with high intake of polyunsaturated fats. In a subset of 1,658 cases and 1,803 controls, specific fatty acids were examined, and docosahexaenoic acid was associated with risk of high-grade disease while trans-fatty acids (TFA) 18:1 and TFA 18:2 were inversely associated with risk of high-grade disease. These large-scale studies suggest a complex relationship between nutrients such as fat and risk of prostate cancer.[39,40]

The explanation for this possible association between prostate cancer and dietary fat is unknown. Several hypotheses have been advanced, including the following:

  1. Dietary fat may increase serum androgen levels, thereby increasing prostate cancer risk. This hypothesis is supported by observations from South Africa and the United States that changes in dietary fat intake change urinary and serum levels of androgens.[41,42]
  2. Certain types of fatty acids or their metabolites may initiate or promote prostate carcinoma development. The evidence for this hypothesis is conflicting, but one study suggests that linoleic acid (omega-6 polyunsaturated fatty acid) may stimulate prostate cancer cells, while omega-3 fatty acids inhibit cell growth.[43]
  3. An observation made in an animal model is that male offspring of pregnant rats who are fed a high-fat diet will develop prostate cancer at a higher rate than animals who are fed a low-fat diet.[44] This observation may explain some of the variations in prostate cancer incidence and mortality among ethnic groups; an observation has been made that first trimester androgen levels in pregnant Black men are higher than those in White men.[45]

Dairy and Calcium Intake

A meta-analysis of ten cohort studies (eight from the United States and two from Europe) concluded that men with the highest intake of dairy products (relative risk [RR], 1.11; 95% confidence interval [CI], 1.00–1.22; P = .04) and calcium (RR, 1.39; 95% CI, 1.09–1.77; P = .18) were more likely to develop prostate cancer than men with the lowest intake. The pooled RRs of advanced prostate cancer were 1.33 (95% CI, 1.00–1.78; P = .055) for the highest versus lowest intake categories of dairy products and 1.46 (95% CI, 0.65–3.25; P > .2) for the highest versus lowest intake categories of calcium. High intake of dairy products and calcium may be associated with an increased risk of prostate cancer, although the increase may be small.[46]

Multivitamin Use

Regular multivitamin use has not been associated with the risk of early or localized prostate cancer. However, in this large (295,344 men) study, there was a statistically significantly increased risk of advanced and fatal prostate cancer among men with excessive use of multivitamins.[47]

Folate

The Aspirin/Folate Polyp Prevention Study, a placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas, was conducted between July 6, 1994, and December 31, 2006. In a secondary analysis, the authors addressed the effect of folic acid supplementation on the risk of prostate cancer. Participants were followed for up to 10.8 (median, 7.0; interquartile range, 6.0–7.8) years and asked periodically to report all illnesses and hospitalizations.[48] Supplementation with 1 mg of folic acid was associated with an increased risk of prostate cancer. However, dietary and plasma levels among nonmultivitamin users were inversely associated with risk. These findings highlight the potentially complex role of folate in prostate carcinogenesis.[48,49]

Cadmium Exposure

Cadmium exposure is occupationally associated with nickel-cadmium batteries and cadmium recovery plant smelters and is associated with cigarette smoke.[50] The earliest studies of this agent documented an apparent association with prostate cancer, but better-designed studies have failed to note an association.[51,52]

Dioxin Exposure

Dioxin (2,3,7,8 tetrachlorodibenzo-p-dioxin or TCDD) is a contaminant of an herbicide used in Vietnam. This agent is similar to many components of herbicides used in farming. A review of the linkage between dioxin and prostate cancer risk, by the National Academy of Sciences Institute of Medicine Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides, found only two articles on prostate cancer with sufficient numbers of cases and follow-up to allow analysis.[53,54] The analysis of all available data suggests that the association between dioxin exposure and prostate cancer is not conclusive.[55]

Prostatitis

Several case-control and cohort studies, as well as two meta-analyses, suggested a significant but modest increase in the risk of prostate cancer in men with prostatitis (RR, 1.6) and in those with a history of syphilis or gonorrhea (RR, 1.4).[56,57] However, PSA values can be elevated with prostatitis, leading to more prostate biopsies and a greater likelihood of making the diagnosis of cancer. This is an example of ascertainment bias, and this bias can be significant in prostate cancer. Any factor associated with an elevation in serum PSA would be expected to lead to more biopsies being performed, and consequently an artifactual elevation in prostate cancer diagnoses. Despite a significant body of work relating inflammation to cancer, a cause and effect relationship has not been established between prostatitis and prostate cancer.[56,57]

References
  1. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
  2. Steinberg GD, Carter BS, Beaty TH, et al.: Family history and the risk of prostate cancer. Prostate 17 (4): 337-47, 1990. [PUBMED Abstract]
  3. Grönberg H, Isaacs SD, Smith JR, et al.: Characteristics of prostate cancer in families potentially linked to the hereditary prostate cancer 1 (HPC1) locus. JAMA 278 (15): 1251-5, 1997. [PUBMED Abstract]
  4. Carter BS, Steinberg GD, Beaty TH, et al.: Familial risk factors for prostate cancer. Cancer Surv 11: 5-13, 1991. [PUBMED Abstract]
  5. Schaid DJ, McDonnell SK, Blute ML, et al.: Evidence for autosomal dominant inheritance of prostate cancer. Am J Hum Genet 62 (6): 1425-38, 1998. [PUBMED Abstract]
  6. Bauer JJ, Srivastava S, Connelly RR, et al.: Significance of familial history of prostate cancer to traditional prognostic variables, genetic biomarkers, and recurrence after radical prostatectomy. Urology 51 (6): 970-6, 1998. [PUBMED Abstract]
  7. Tangen CM, Goodman PJ, Till C, et al.: Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials. J Clin Oncol 34 (36): 4338-4344, 2016. [PUBMED Abstract]
  8. Imperato-McGinley J, Gautier T, Zirinsky K, et al.: Prostate visualization studies in males homozygous and heterozygous for 5 alpha-reductase deficiency. J Clin Endocrinol Metab 75 (4): 1022-6, 1992. [PUBMED Abstract]
  9. Isaacs JT: Hormonal balance and the risk of prostatic cancer. J Cell Biochem Suppl 16H: 107-8, 1992. [PUBMED Abstract]
  10. Peters CA, Walsh PC: The effect of nafarelin acetate, a luteinizing-hormone-releasing hormone agonist, on benign prostatic hyperplasia. N Engl J Med 317 (10): 599-604, 1987. [PUBMED Abstract]
  11. Kyprianou N, Isaacs JT: Expression of transforming growth factor-beta in the rat ventral prostate during castration-induced programmed cell death. Mol Endocrinol 3 (10): 1515-22, 1989. [PUBMED Abstract]
  12. Andriole GL, Bostwick DG, Brawley OW, et al.: Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362 (13): 1192-202, 2010. [PUBMED Abstract]
  13. Thompson IM, Goodman PJ, Tangen CM, et al.: The influence of finasteride on the development of prostate cancer. N Engl J Med 349 (3): 215-24, 2003. [PUBMED Abstract]
  14. Ellis L, Nyborg H: Racial/ethnic variations in male testosterone levels: a probable contributor to group differences in health. Steroids 57 (2): 72-5, 1992. [PUBMED Abstract]
  15. Ross RK, Bernstein L, Lobo RA, et al.: 5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet 339 (8798): 887-9, 1992. [PUBMED Abstract]
  16. Wu AH, Whittemore AS, Kolonel LN, et al.: Serum androgens and sex hormone-binding globulins in relation to lifestyle factors in older African-American, white, and Asian men in the United States and Canada. Cancer Epidemiol Biomarkers Prev 4 (7): 735-41, 1995 Oct-Nov. [PUBMED Abstract]
  17. Roddam AW, Allen NE, Appleby P, et al.: Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 100 (3): 170-83, 2008. [PUBMED Abstract]
  18. Bunker CH, Patrick AL, Konety BR, et al.: High prevalence of screening-detected prostate cancer among Afro-Caribbeans: the Tobago Prostate Cancer Survey. Cancer Epidemiol Biomarkers Prev 11 (8): 726-9, 2002. [PUBMED Abstract]
  19. Optenberg SA, Thompson IM, Friedrichs P, et al.: Race, treatment, and long-term survival from prostate cancer in an equal-access medical care delivery system. JAMA 274 (20): 1599-605, 1995 Nov 22-29. [PUBMED Abstract]
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  21. Wynder EL, Mabuchi K, Whitmore WF: Epidemiology of cancer of the prostate. Cancer 28 (2): 344-60, 1971. [PUBMED Abstract]
  22. Armstrong B, Doll R: Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 15 (4): 617-31, 1975. [PUBMED Abstract]
  23. Rose DP, Connolly JM: Dietary fat, fatty acids and prostate cancer. Lipids 27 (10): 798-803, 1992. [PUBMED Abstract]
  24. Haenszel W, Kurihara M: Studies of Japanese migrants. I. Mortality from cancer and other diseases among Japanese in the United States. J Natl Cancer Inst 40 (1): 43-68, 1968. [PUBMED Abstract]
  25. Shimizu H, Ross RK, Bernstein L, et al.: Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 63 (6): 963-6, 1991. [PUBMED Abstract]
  26. Wang Y, Corr JG, Thaler HT, et al.: Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet. J Natl Cancer Inst 87 (19): 1456-62, 1995. [PUBMED Abstract]
  27. Connolly JM, Coleman M, Rose DP: Effects of dietary fatty acids on DU145 human prostate cancer cell growth in athymic nude mice. Nutr Cancer 29 (2): 114-9, 1997. [PUBMED Abstract]
  28. Ross RK, Shimizu H, Paganini-Hill A, et al.: Case-control studies of prostate cancer in blacks and whites in southern California. J Natl Cancer Inst 78 (5): 869-74, 1987. [PUBMED Abstract]
  29. Kolonel LN, Yoshizawa CN, Hankin JH: Diet and prostatic cancer: a case-control study in Hawaii. Am J Epidemiol 127 (5): 999-1012, 1988. [PUBMED Abstract]
  30. Whittemore AS, Kolonel LN, Wu AH, et al.: Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. J Natl Cancer Inst 87 (9): 652-61, 1995. [PUBMED Abstract]
  31. Giovannucci E: Epidemiologic characteristics of prostate cancer. Cancer 75 (Suppl 7): 1766-77, 1995.
  32. Mettlin C, Selenskas S, Natarajan N, et al.: Beta-carotene and animal fats and their relationship to prostate cancer risk. A case-control study. Cancer 64 (3): 605-12, 1989. [PUBMED Abstract]
  33. Severson RK, Nomura AM, Grove JS, et al.: A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res 49 (7): 1857-60, 1989. [PUBMED Abstract]
  34. Zhou JR, Blackburn GL: Bridging animal and human studies: what are the missing segments in dietary fat and prostate cancer? Am J Clin Nutr 66 (6 Suppl): 1572S-1580S, 1997. [PUBMED Abstract]
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  36. Bairati I, Meyer F, Fradet Y, et al.: Dietary fat and advanced prostate cancer. J Urol 159 (4): 1271-5, 1998. [PUBMED Abstract]
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  38. Wynder EL, Cohen LA: Correlating nutrition to recent cancer mortality statistics. J Natl Cancer Inst 89 (4): 324, 1997. [PUBMED Abstract]
  39. Kristal AR, Till C, Platz EA, et al.: Serum lycopene concentration and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev 20 (4): 638-46, 2011. [PUBMED Abstract]
  40. Kristal AR, Arnold KB, Neuhouser ML, et al.: Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol 172 (5): 566-77, 2010. [PUBMED Abstract]
  41. Hill P, Wynder EL, Garbaczewski L, et al.: Diet and urinary steroids in black and white North American men and black South African men. Cancer Res 39 (12): 5101-5, 1979. [PUBMED Abstract]
  42. Hämäläinen E, Adlercreutz H, Puska P, et al.: Diet and serum sex hormones in healthy men. J Steroid Biochem 20 (1): 459-64, 1984. [PUBMED Abstract]
  43. Rose DP, Connolly JM: Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines. Prostate 18 (3): 243-54, 1991. [PUBMED Abstract]
  44. Kondo Y, Homma Y, Aso Y, et al.: Promotional effect of two-generation exposure to a high-fat diet on prostate carcinogenesis in ACI/Seg rats. Cancer Res 54 (23): 6129-32, 1994. [PUBMED Abstract]
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  46. Gao X, LaValley MP, Tucker KL: Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer Inst 97 (23): 1768-77, 2005. [PUBMED Abstract]
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Opportunities for Prevention

Hormonal Prevention

The Prostate Cancer Prevention Trial (PCPT), a large randomized placebo-controlled trial of finasteride (an inhibitor of alpha-reductase), was performed in 18,882 men aged 55 years or older. At 7 years, the incidence of prostate cancer was 18.4% in the finasteride group versus 24.4% in the placebo group, a relative risk reduction (RRR) of 24.8% (95% confidence interval [CI], 18.6%–30.6%; P < .001). The finasteride group had more patients with Gleason grade 7 to 10, but the clinical significance of Gleason scoring is uncertain in conditions of androgen deprivation.[1] High-grade cancers (Gleason score 7–10) were noted in 6.4% of finasteride patients, compared with 5.1% of men who received placebo, yielding a relative risk (RR) of 1.27 (95% CI, 1.07–1.50). The increase in high-grade tumors was seen within 1 year of finasteride exposure and did not increase during this time period.[2]

Finasteride decreases the risk of prostate cancer but may also alter the detection of disease through effects on prostate-specific antigen (PSA), prostate digital rectal examination (DRE), and decreased prostate volume (24%), creating a detection bias.[3] Adjustment of PSA in men taking finasteride preserves the performance characteristics for cancer detection.[4]

Examination of the outcomes of the PCPT found that finasteride significantly reduced the risk of high-grade prostatic intraepithelial neoplasia (HGPIN); HGPIN alone was reduced by 15% (RR, 0.85; 95% CI, 0.73–0.99) and HGPIN with prostate cancer was reduced by 31% (RR, 0.69; 95% CI, 0.56–0.85).[3,5] The concern that finasteride may increase the risk of high-grade cancer prompted an examination of the rate of cancer development in the PCPT. While a gradual and progressive increase in the number of high-grade tumors would have been expected over the study duration of 7 years, when compared with placebo, this was not the case. The increase in high-grade tumors was seen within 1 year of finasteride exposure and did not increase during this time period.[2] An analysis of the PCPT data adjusted for the sources of detection bias found that finasteride reduced the incidence of Gleason score 5 to 7 and Gleason score 3 to 4 prostate cancer, but not Gleason score 2 to 3 or Gleason score 8 to 10. The reduction in the incidence of Gleason score 7 (22%) was less than the reduction in the incidence of Gleason 5 score (58%) and Gleason score 6 (52%).[6] An analysis using different methodologies found an overall reduction of both low-grade (Gleason score <6) and high-grade (Gleason score >7) cancers.[7]

A follow-up analysis of the PCPT of finasteride mapped study participants with the National Death Index, allowing for an analysis of prostate cancer-specific mortality. With 296,842 person-years of follow-up and a median follow-up of 18.4 years, of the 9,423 men randomly assigned to the finasteride group, there were 3,048 deaths of which 42 were caused by prostate cancer; of the 9,457 men randomly assigned to the placebo group, there were 2,979 deaths of which 56 were caused by prostate cancer. The 25% reduction in risk of prostate cancer death with finasteride was not statistically significant (hazard ratio, finasteride vs. placebo, 0.75; 95% CI, 0.50–1.12). It was concluded that the early concern for an increased risk of high-grade prostate cancer with finasteride was not borne out. In this study, it was notable that, of the 61 prostate cancer deaths for which original Gleason grading was available, 23 (38%) of the prostate cancer deaths were seen in men whose original biopsy Gleason grade was less than or equal to 6.[8]

A retrospective, population-based, cohort study from the U.S. Department of Veterans Affairs health care system examined the impact of 5-alpha reductase inhibitor (5-ARI) use before prostate cancer diagnosis on prostate cancer-specific mortality.[9] The authors found that prediagnostic use of 5-ARIs was associated with a delayed diagnosis (median time from first elevated PSA was 3.6 years for men who received 5-ARIs versus 1.4 years for non–5-ARI users) and worsened cancer-specific outcomes (e.g., higher grade, higher clinical stage, more with positive nodes, and higher rates of metastatic disease) in men with prostate cancer. A subsequent letter to the editor pointed out the following challenges with the analysis:

  1. A 39% improvement in prostate cancer mortality with a 2-year earlier diagnosis and with only 5.9 years of follow-up is implausible, given that the very best reduction in prostate cancer mortality in a randomized clinical trial was 20%.
  2. Because the study could not assess 5-ARI medication adherence, PSA misadjustment was a serious concern.
  3. Because men treated with 5-ARIs are very different than those not treated (i.e., more urinary symptoms, older, larger prostates, etc.), major differences in baseline characteristics, as reported in the study, prevented adequate adjustment in outcomes.
  4. As demonstrated by the PCPT, because finasteride (a 5-ARI) prevents a substantial proportion of low-grade tumors, a greater proportion of high-grade tumors would be expected.
  5. Because national treatment guidelines recommend 5-ARIs for men with larger prostates, which have higher PSA values, and as prostate cancers are more commonly missed in larger prostates (and may be identified at a subsequent biopsy, often with a magnetic resonance imaging-directed biopsy), a later diagnosis would be common in this patient population.
  6. The authors’ analysis did not adjust for survival bias; men not receiving a 5-ARI had an earlier diagnosis, and therefore, an inherent longer survival.

When taken together, these biases call into question the conclusions, which appear to be at odds with the prostate cancer–specific mortality outcomes of the randomized PCPT.

The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial randomly assigned 8,231 men aged 50 to 75 years at higher risk of prostate cancer (i.e., PSA 2.5–10.0 ng/mL) with one recent negative prostate biopsy to dutasteride at 0.5 mg daily or to placebo. The primary end point was prostate cancer diagnosed by prostate biopsy at 2 years and 4 years after randomization. After 4 years, among the 6,729 men (82% of initial population) who had at least one prostate biopsy, 25.1% of the placebo group and 19.9% of the dutasteride group had been diagnosed with prostate cancer, a statistically significant difference (absolute risk reduction, 5.1% and RRR, 22.8% [95% CI, 15.2%–29.8%]). The RRR in years 3 to 4 was similar to the RRR in years 1 to 2. The difference between the groups was entirely due to a reduction in prostate cancers with Gleason score 5 to 7. For years 3 to 4 there was a statistically significant increase in the dutasteride group compared with the placebo group in prostate cancers with Gleason score 8 to 10 (12 cancers in the dutasteride group vs. 1 cancer in the placebo group).[10]

Overall, there was no statistically significant difference in high-grade tumors for Gleason score 8 to 10 cancers in years 1 to 4 (29 tumors in the dutasteride group vs. 19 tumors in the placebo group, 0.9% vs. 0.6%; P = .15). However, in a retrospective analysis there was a statistically significant difference between years 3 to 4. Because this is a small retrospective subgroup, the finding of an increase in Gleason score 8 to 10 cancers is of uncertain validity. However, the finding of no reduction in these cancers is more significant.[10]

While long-term data are unavailable for dutasteride as a cancer prevention agent, evidence is now available that finasteride does not have a significant effect on overall survival or prostate cancer–specific survival. Its effect is primarily in preventing the diagnosis of prostate cancer and the subsequent events (staging, treatment, follow-up, and management of treatment-related side effects) after diagnosis.

Agents that are used for hormonal therapy of existing prostate cancers would be unsuitable for prostate cancer chemoprevention because of the cost and wide variety of side effects including sexual dysfunction, osteoporosis, and vasomotor symptoms (hot flushes).[11] Newer antiandrogens may play a role as preventive agents in the future.[12]

A Cochrane systematic review of all published studies of clinical outcome investigations of the prostate preventive effects of 5-ARIs through 2010 that were at least 1 year in duration concluded that finasteride and dutasteride reduce the risk of being diagnosed with prostate cancer among men who are screened regularly for prostate cancer. The review also concluded that mortality effects could not be assessed from these studies and that persistent use of these agents increased sexual and erectile dysfunction. The review was based on MEDLINE and Cochrane Collaboration Library computerized searches through June 2010 using the Medical Subject Headings terms and text words finasteride, dutasteride, neoplasms, azasteroids, reductase inhibitors, and enzyme inhibitors to identify randomized trials. Eight studies met the inclusion criteria. Only the PCPT and the REDUCE study were designed to assess the impact of 5-ARIs on prostate cancer period prevalence. Reviews of all eight studies concluded that compared with placebo, 5-ARIs resulted in 25% RR reduction in prostate cancers detected for cause (RR, 0.75; 95% CI, 0.67–0.83 and 1.4% absolute risk reduction [3.5% vs. 4.9%]). Six trials of 5-ARIs versus placebo assessed prostate cancers detected overall. Among these there was a 26% RR reduction favoring 5-ARIs (RR, 0.74; 95% CI, 0.55–1.00 and 2.9% absolute risk reduction [6.3% vs. 9.2%]). There were reductions across age, race, and family history. One placebo-controlled trial of men considered at greater risk for prostate cancer based on age, elevated PSA, and previous suspicion of prostate cancer leading to a prostate biopsy reported that dutasteride did not reduce prostate cancers detected for cause based on needle biopsy but did reduce risk of overall incident prostate cancer detected by biopsy by 23% (RR, 0.77; 95% CI, 0.7–0.85 and absolute risk reduction, 16.1% vs. 20.8%). There were reductions across age, family history of prostate cancer, PSA level, and prostate volume subgroups. The Cochrane review defined for cause cancers as follows:

  1. Suspected clinically from symptoms, abnormal DRE, or PSA and confirmed on biopsy.
  2. Study protocol recommended biopsy, but it was not done and the end-of-study biopsy showed prostate cancer.
  3. The end-of-study biopsy with PSA less than 4 ng/mL and/or suspicious DRE showed prostate cancer.[13]

Dietary Prevention With Fruit, Vegetables, and a Low-fat Diet

Results from studies of the association between dietary intake of fruits and vegetables and risk of prostate cancer are not consistent. A study evaluated 1,619 prostate cancer cases and 1,618 controls in a multicenter, multiethnic population. The study found that intake of legumes and yellow-orange and cruciferous vegetables was associated with a lower risk of prostate cancer.

The European Prospective Investigation into Cancer and Nutrition examined the association between fruit and vegetable intake and subsequent prostate cancer. After an average follow-up of 4.8 years, 1,104 men developed prostate cancer among the 130,544 male participants. No statistically significant associations were observed for fruit intake, vegetable intake, cruciferous vegetable intake, or the intake of fruits and vegetables combined.[14]

One study of dietary intervention over a 4-year period with reduced fat and increased consumption of fruit, vegetables, and fiber had no impact on serum PSA levels.[15] It is unknown whether dietary modification through the use of a low-fat, plant-based diet will reduce prostate cancer risk. While this outcome is unknown, multiple additional benefits may be observed in patients following such a diet, including a lower risk of hyperlipidemia, better control of blood pressure, and a lower risk of cardiovascular disease—all of which may merit adoption of such a diet.

Chemoprevention

While several agents, including alpha-tocopherol, selenium, lycopene, difluoromethylornithine,[16–20] vitamin D,[21–23] and isoflavonoids,[24,25] have shown potential in either clinical or laboratory studies for chemoprevention of prostate cancer. However, the correlations of cancer prevention with these agents are increasingly of concern given the statistically significant increased risk of prostate cancer with alpha-tocopherol in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and the lack of preventive effect (actually, a nonsignificant increase in prostate cancer risk) with selenium.

Chemoprevention with selenium and vitamin E

The SELECT (NCT00006392) was a large randomized placebo-controlled trial of vitamin E and selenium. It showed no reduction in prostate cancer period prevalence, but an increased risk of prostate cancer with vitamin E alone.[26]

Compared with the placebo group in which 529 men developed prostate cancer, there was a statistically significant increase in prostate cancer in the vitamin E group (620 cases), but not in the selenium plus vitamin E group (555 cases) or in the selenium group (575 cases). The magnitude of increase in prostate cancer risk with vitamin E alone was 17%. Of interest, the statistically increased risk of prostate cancer among men receiving vitamin E was seen after study supplements had been discontinued suggesting a longer-term effect of this agent.[26]

Chemoprevention with lycopene

Evidence exists that a diet with a high intake of fruits and vegetables is associated with a lower risk of cancer. Which, if any, micronutrients may account for this reduction is unknown. One group of nutrients often postulated as having chemoprevention properties is the carotenoids. Lycopene is the predominant circulating carotenoid in Americans and has a number of potential activities, including an antioxidant effect.[27] It is encountered in a number of vegetables, most notably tomatoes, and is best absorbed if these products are cooked and in the presence of dietary fats or oils.

The earliest studies of the association of lycopene and prostate cancer risk were generally negative before 1995 with only one study of 180 case-control patients showing a reduced risk.[28–31] In 1995, an analysis of the Physicians’ Health Study found a one-third reduction in prostate cancer risk in the group of men with the highest consumption of tomato products when compared with the group with the lowest level of consumption, which was attributed to the lycopene content of these vegetables.[32] This large analysis prompted several subsequent studies, the results of which were mixed.[33,34] A review of the published data concluded that the evidence is weak that lycopene is associated with a reduced risk because previous studies were not controlled for total vegetable intake (i.e., separating the effect of tomatoes from vegetables), dietary intake instruments are poorly able to quantify lycopene intake, and other potential biases.[35] Specific dietary supplementation with lycopene remains to be demonstrated to reduce prostate cancer risk. In the largest prospective study to date, the PCPT, lycopene was not associated with any reduction in risk of prostate cancer among 9,559 men studied. Similarly, there was no relationship between lycopene serum concentrations and risk of prostate cancer.[36,37]

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  34. Key TJ, Silcocks PB, Davey GK, et al.: A case-control study of diet and prostate cancer. Br J Cancer 76 (5): 678-87, 1997. [PUBMED Abstract]
  35. Kristal AR, Cohen JH: Invited commentary: tomatoes, lycopene, and prostate cancer. How strong is the evidence? Am J Epidemiol 151 (2): 124-7; discussion 128-30, 2000. [PUBMED Abstract]
  36. Kristal AR, Till C, Platz EA, et al.: Serum lycopene concentration and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev 20 (4): 638-46, 2011. [PUBMED Abstract]
  37. Kristal AR, Arnold KB, Neuhouser ML, et al.: Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol 172 (5): 566-77, 2010. [PUBMED Abstract]

Latest Updates to This Summary (04/09/2025)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Incidence and Mortality of Prostate Cancer

Updated statistics with estimated new cases and deaths for 2025 (cited American Cancer Society as reference 1).

This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about prostate cancer prevention. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

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PDQ® Screening and Prevention Editorial Board. PDQ Prostate Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: /types/prostate/hp/prostate-prevention-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389405]

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Hormone Therapy for Prostate Cancer

Hormone Therapy for Prostate Cancer

What are male sex hormones?

Hormones are substances that are made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs.

Androgens (male sex hormones) are a class of hormones that control the development and maintenance of male characteristics. The most abundant androgens in men are testosterone and dihydrotestosterone (DHT). 

Androgens are required for normal growth and function of the prostate, a gland in the male reproductive system that helps make semen. Androgens are also necessary for prostate cancers to grow. Androgens promote the growth of both normal and cancerous prostate cells by binding to and activating the androgen receptor, a protein that is expressed in prostate cells (1). Once activated, the androgen receptor stimulates the expression of specific genes that cause prostate cells to grow (2).

Almost all testosterone is produced in the testicles; a small amount is produced by the adrenal glands. Although prostate cells do not normally make testosterone, some prostate cancer cells acquire the ability to do so (3).

How does hormone therapy work against prostate cancer?

Early in their development, prostate cancers need androgens to grow. Hormone therapies, which are treatments that decrease androgen levels or block androgen action, can inhibit the growth of such prostate cancers, which are therefore called castrate-sensitive prostate cancer. Such cancers may also be described as being androgen dependent, androgen sensitive, castration sensitive, or hormone sensitive.

Most prostate cancers eventually stop responding to hormone therapy and become castration (or castrate) resistant. That is, they continue to grow even when androgen levels in the body are extremely low or undetectable. In the past, these tumors were also called hormone resistant, androgen independent, or hormone refractory; however, these terms are rarely used now because the tumors are not truly independent of androgens for their growth. In fact, some newer hormone therapies have become available that can be used to treat tumors that have become castration resistant.

What types of hormone therapy are used for prostate cancer?

Hormone therapy for prostate cancer can block the production or use of androgens (4). Currently available treatments can do so in several ways:

  • reducing androgen production by the testicles
  • blocking the action of androgens throughout the body
  • blocking androgen production (synthesis) throughout the body including by prostate cancer cells
Illustration of the male endocrine system focusing on hormone regulation. It shows the brain, hypothalamus, and pituitary gland producing LHRH, which stimulates the release of LH. Arrows indicate the feedback loop of hormone regulation within the body.

Androgen production in men. Drawing shows that testosterone production is regulated by luteinizing hormone (LH) and luteinizing hormone-releasing hormone (LHRH). The hypothalamus releases LHRH, which stimulates the release of LH from the pituitary gland. LH acts on specific cells in the testes to produce the majority of testosterone in the body. Most of the remaining androgens are produced by the adrenal glands. Androgens are taken up by prostate cells, where they either bind to the androgen receptor directly or are converted to dihydrotestosterone (DHT), which has a greater binding affinity for the androgen receptor than testosterone.

Credit: © Terese Winslow

Treatments that reduce androgen production by the testicles are the most commonly used hormone therapies for prostate cancer and the first type of hormone therapy that most people with prostate cancer receive. This form of hormone therapy, which is called androgen deprivation therapy, or ADT, includes:

  • Orchiectomy, a surgical procedure to remove both testicles. Removal of the testicles, called surgical castration, can reduce the level of testosterone in the blood by 90% to 95% (5). 
  • Drugs called luteinizing hormone-releasing hormone (LHRH) agonists, which prevent the pituitary gland from secreting a hormone called luteinizing hormone. LHRH agonists, which are sometimes called LHRH analogs, are synthetic proteins that are structurally similar to LHRH and bind to the LHRH receptor in the pituitary gland. (LHRH is also known as gonadotropin-releasing hormone or GnRH, so LHRH agonists are also called GnRH agonists or GnRH analogs.)

    Normally, when androgen levels in the body are low, the hypothalamus releases LHRH. This stimulates the pituitary gland to produce luteinizing hormone, which in turn stimulates the testicles to produce androgens. LHRH agonists, like the body’s own LHRH, initially stimulate the production of luteinizing hormone. However, the continued presence of high levels of LHRH agonists actually causes the pituitary gland to stop producing luteinizing hormone. As a result, the testicles are not stimulated to produce androgens.

    Treatment with an LHRH agonist is called medical castration or chemical castration. But unlike surgical castration (orchiectomy), medical castration is reversible. Once treatment is stopped, androgen production usually resumes.

    LHRH agonists are given by injection or are implanted under the skin. LHRH agonists that are approved to treat prostate cancer in the United States include leuprolide (Lupron Depot, Eligard, Camcevi), goserelin (Zoladex), and triptorelin (Trelstar).

    When patients receive an LHRH agonist for the first time, they may experience a phenomenon called “testosterone flare.” This is a temporary increase in testosterone level that occurs because LHRH agonists briefly cause the pituitary gland to secrete extra luteinizing hormone before blocking its release. The flare may worsen clinical symptoms (such as bone pain, ureter or bladder outlet obstruction, and spinal cord compression).

  • Drugs called LHRH antagonists, which are another form of medical castration. LHRH antagonists (also called GnRH antagonists) prevent LHRH from binding to its receptors in the pituitary gland. This in turn prevents the secretion of luteinizing hormone, which stops the testicles from producing androgens. Unlike LHRH agonists, LHRH antagonists do not cause a testosterone flare.

    LHRH antagonists that are approved to treat advanced prostate cancer in the United States include degarelix (Firmagon), which is given by injection, and relugolix (Orgovyx), which is a pill that is taken by mouth.

Treatments that block the action of androgens in the body, called antiandrogen therapies, androgen receptor blockers, or androgen receptor antagonists. Such treatments work by competing with androgens for binding to androgen receptors. By keeping androgens from binding to androgen receptors, these treatments reduce the ability of androgens to promote prostate cancer cell growth. 

Androgen receptor blockers are typically used together with ADT (orchiectomy or an LHRH agonist) because the combination both reduces androgen levels and keeps any remaining androgen from binding to androgen receptors. The combination is often referred to as combined androgen blockade, complete androgen blockade, maximal androgen blockade, or total androgen blockade. In addition to being used as hormone therapy for prostate cancer, androgen receptor blockers are sometimes used for a few weeks at the start of ADT to prevent testosterone flares.

Androgen receptor blockers that are approved in the United States to treat prostate cancer include the “first-generation” drugs flutamide, bicalutamide (Casodex), and nilutamide (Nilandron), and the “second-generation” drugs enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). The second-generation drugs bind to and block the androgen receptor more strongly and specifically than the first-generation drugs (6). Darolutamide is the only androgen receptor blocker that does not cross the blood-brain barrier in humans, which may result in fewer central nervous system–related side effects. Androgen receptor blockers are given as pills to be swallowed.

Treatments that block the production of androgens throughout the body, known as androgen synthesis inhibitors. Like ADT, androgen synthesis inhibitors prevent androgen production by the testicles; unlike ADT they also prevent androgen production by the adrenal glands and prostate cancer cells. Even though only small amounts of androgens are produced outside the testicles, the low levels that are still produced can be enough to support the growth of some prostate cancers.

Androgen synthesis inhibitors lower testosterone levels to a greater extent than any other known treatment. They do so by inhibiting an enzyme called CYP17. This enzyme, which is found in testicular, adrenal, and prostate tumor tissues, is necessary for the body to produce testosterone.

Androgen synthesis inhibitors approved in the United States include abiraterone (Yonsa, Zytiga) and ketoconazole. Both are given as pills to be swallowed.

Abiraterone is used in combination with prednisone to treat metastatic prostate cancer, both castration-sensitive and castration-resistant. Ketoconazole is approved for indications other than prostate cancer but is sometimes used off-label as second-line treatment for castration-resistant prostate cancer, although such use is rare given the availability of second-generation androgen receptor blockers.

How is hormone therapy used to treat castration-sensitive prostate cancer?

Hormone therapy may be used in several ways to treat castration-sensitive prostate cancer, including for:

Early-stage prostate cancer with an intermediate or high risk of recurrence. Men who are having radiation therapy to treat early-stage prostate cancer that has an unfavorable intermediate or high risk of recurrence often receive ADT as well. And ADT may be used after prostatectomy in men who have high-risk node-positive disease (7, 8). 

Enzalutamide Gets Added Approval for Prostate Cancer That Hasn’t Spread

The approval covers people whose cancer is at high risk of coming back.

Relapsed/recurrent prostate cancer. Hormone therapy is often used alone for people who have a recurrence of prostate cancer after earlier treatment with radiation or surgery. Hormone therapy is standard treatment for those who have a symptomatic recurrence (as documented by CT, MRI, PSMA PET scan, or bone scan) and may also be recommended for some people who have a “biochemical recurrence” (a rise in prostate-specific antigen [PSA] level after treatment with surgery or radiation), especially if the PSA level is rising rapidly. 

Advanced or metastatic prostate cancer. ADT used alone was for many years the standard treatment for men who, at the time of their initial prostate cancer diagnosis, are found to have castration-sensitive metastatic disease (i.e., disease that has spread to other parts of the body) (9). Now, such men are treated with ADT plus another type of hormone therapy (abiraterone, enzalutamide, or apalutamide) or ADT plus the chemotherapy drug docetaxel (Taxotere) and a second-generation androgen receptor blocker, such as abiraterone or darolutamide. Some of these men, especially those with extensive metastases, may be treated with ADT plus chemotherapy plus another type of hormone therapy (10). 

Although hormone therapy can delay progression of metastatic disease and may extend survival, it can also have side effects. Men should discuss the risks and potential benefits of hormone therapy with their doctors and potential ways to reduce some side effects. 

Palliation of symptoms. Hormone therapy is sometimes used alone for palliation or prevention of local symptoms in men with localized prostate cancer who are not candidates for surgery or radiation therapy (11). Such men include those with a limited life expectancy, those with locally advanced tumors, and/or those with other serious health conditions.

How will I know that my hormone therapy is working?

Doctors cannot predict how long hormone therapy will be effective in suppressing the growth of any individual man’s prostate cancer. Therefore, men who take hormone therapy for more than a few months are regularly tested to determine the level of PSA in their blood. An increase in PSA level may indicate that a man’s cancer has started growing again or become resistant to the hormone therapy that is currently being used.

How is castration-resistant prostate cancer treated?

Treatments for castration-resistant prostate cancer include:

People with castration-resistant prostate cancer who receive these treatments will continue to receive ADT (e.g., an LHRH agonist) to keep testosterone levels low, because an increase in testosterone could lead to tumor progression in some men (12).

What is intermittent ADT?

Researchers have investigated whether a technique called intermittent androgen deprivation can delay the development of hormone resistance. With intermittent androgen deprivation, hormone therapy is given in cycles with breaks between drug administrations rather than continuously, particularly in people with a biochemical recurrence. The goal of intermittent androgen deprivation is to delay the development of hormone resistance. An additional potential benefit of this approach is that the temporary break from the side effects of hormone therapy may improve a man’s quality of life. No trials have compared intermittent ADT with continuous ADT.

What are the side effects of hormone therapy for prostate cancer?

Because androgens affect many other organs besides the prostate, ADT can have a wide range of side effects (4, 13), including:

Antiandrogens can cause diarrhea, breast tenderness, nausea, hot flashes, loss of libido, and erectile dysfunction. The antiandrogen flutamide may damage the liver, and enzalutamide and apalutamide may cause fractures. Darolutamide may avoid some central nervous system–related side effects seen with enzalutamide and apalutamide, such as seizures and falls.

Androgen synthesis inhibitors can cause diarrhea, itching and rashes, fatigue, erectile dysfunction (with long-term use), and, potentially, liver damage.

Although the addition of ADT to radiation therapy has been shown to increase survival for men with high-risk prostate cancer, it worsens some adverse effects of radiotherapy, particularly sexual side effects and vitality (14). The risk of side effects increases the longer a person is on hormone therapy (13).

What can be done to reduce the side effects of hormone therapy for prostate cancer?

Men who lose bone mass during long-term hormone therapy may be prescribed drugs to slow or reverse this loss. The drugs zoledronic acid (Zometa) and alendronate (Fosamax) (both of which belong to a class of drugs called bisphosphonates) can be used to increase bone mineral density in men who are undergoing hormone therapy (15, 16), as can a newer drug, denosumab (Prolia), which increases bone mass through a different mechanism (17). However, drugs to treat bone loss are associated with a rare but serious side effect called osteonecrosis of the jaw (12).

Exercise may help reduce some of the side effects of hormone therapy, including bone loss, muscle loss, weight gain, fatigue, and insulin resistance (12, 18). Several clinical trials are examining whether exercise can reverse or prevent side effects of hormone therapy for prostate cancer.

The sexual side effects of hormone therapy for prostate cancer can be some of the most difficult to deal with. Erectile dysfunction drugs such as sildenafil (Viagra) do not usually work for men undergoing hormone therapy because these drugs do not address the loss of libido (sexual desire) that is associated with a lack of androgens.

More information about the sexual side effects of cancer treatment can be found on the Sexual Health Issues in Men with Cancer page.

Most of the sexual and emotional side effects caused by low levels of androgens will eventually go away if a man stops taking hormone therapy. However, particularly for older men and those who received ADT for a long time, testosterone levels may not fully recover and these side effects may not disappear completely. Some physical changes that have developed over time, such as bone loss, will remain after stopping hormone therapy.

Patients should be sure to tell their doctor about all medications and supplements they are taking, including over-the-counter herbal medicines. Some herbal medicines interact with drug metabolizing enzymes in the body, which can adversely affect hormone therapy (19).