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Gestational Trophoblastic Disease Treatment (PDQ®)–Health Professional Version

Gestational Trophoblastic Disease Treatment (PDQ®)–Health Professional Version

General Information About Gestational Trophoblastic Disease

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Gestational trophoblastic disease (GTD) is a broad term encompassing both benign and malignant growths arising from products of conception in the uterus.[1]

Incidence and Mortality

The reported incidence of GTD varies widely worldwide, from a low of 23 per 100,000 pregnancies (Paraguay) to a high of 1,299 per 100,000 pregnancies (Indonesia).[2] However, at least part of this variability is caused by differences in diagnostic criteria and reporting. The reported incidence in the United States is about 110 to 120 per 100,000 pregnancies. In the United States, the reported incidence of choriocarcinoma, the most aggressive form of GTD, is about 2 to 7 per 100,000 pregnancies. The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is about 0.18 per 100,000 women between the ages of 15 years and 49 years.[2]

Risk Factors

Two factors have consistently been associated with an increased risk of GTD:[2]

  • Maternal age.
  • History of hydatidiform mole (HM).

If a woman has been previously diagnosed with an HM, she carries a 1% risk of HM in subsequent pregnancies. This increases to approximately 25% with more than one prior HM. The risk associated with maternal age is bimodal, with increased risk both for mothers younger than 20 years and older than 35 years (and particularly for mothers >45 years). Relative risks are in the range of 1.1 to 11 for both the younger and older age ranges compared with ages 20 to 35 years. However, a population-based HM registry study suggests that the age-related patterns of the two major types of HM—complete and partial HM—are distinct.[3] For more information, see the Cellular Classification of Gestational Trophoblastic Disease section. In that study, the rate of complete HM was highest in women younger than 20 years and then decreased monotonically with age. However, the rates of partial HM increased for the entire age spectrum, suggesting possible differences in etiology. The association with paternal age is inconsistent.[2] A variety of exposures have been examined, with no clear associations found with tobacco smoking, alcohol consumption, diet, and oral contraceptive use.[2]

Clinical Features

GTDs contain paternal chromosomes and are placental, rather than maternal, in origin. The most common presenting symptoms are vaginal bleeding and a rapidly enlarging uterus, and GTD should be considered whenever a premenopausal woman presents with these findings. Because the vast majority of GTD types are associated with elevated human chorionic gonadotropin (hCG) levels, an hCG blood level and pelvic ultrasound are the initial steps in the diagnostic evaluation. In addition to vaginal bleeding and uterine enlargement, other presenting symptoms or signs may include the following:

  • Pelvic pain or sensation of pressure.
  • Anemia.
  • Hyperemesis gravidarum.
  • Hyperthyroidism (secondary to the homology between the beta-subunits of hCG and thyroid-stimulating hormone [TSH], which causes hCG to have weak TSH-like activity).
  • Preeclampsia early in pregnancy.

The most common antecedent pregnancy in GTD is that of an HM.

Choriocarcinoma most commonly follows a molar pregnancy but can follow a normal pregnancy, ectopic pregnancy, or abortion, and it should always be considered when a patient has continued vaginal bleeding in the postdelivery period. Other possible signs include neurologic symptoms (resulting from brain metastases) in a female within the reproductive age group and asymptomatic lesions on routine chest x-ray.

Prognostic Factors and Survivorship

The prognosis for cure of patients with GTDs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM (tumor, node, metastasis) staging system has limited prognostic value.[4] The probability of cure depends on the following:

  • Histological type (invasive mole or choriocarcinoma).
  • Extent of spread of the disease/largest tumor size.
  • Level of serum beta-hCG.
  • Duration of disease from the initial pregnancy event to start of treatment.
  • Number and specific sites of metastases.
  • Nature of antecedent pregnancy.
  • Extent of prior treatment.

Selection of treatment depends on these factors plus the patient’s desire for future pregnancies. Beta-hCG is a sensitive marker to indicate the presence or absence of disease before, during, and after treatment. Given the extremely good therapeutic outcomes of most of these tumors, an important goal is to distinguish patients who need less-intensive therapies from those who require more-intensive regimens to achieve a cure.

References
  1. Ngan HY, Kohorn EI, Cole LA, et al.: Trophoblastic disease. Int J Gynaecol Obstet 119 (Suppl 2): S130-6, 2012. [PUBMED Abstract]
  2. Altieri A, Franceschi S, Ferlay J, et al.: Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol 4 (11): 670-8, 2003. [PUBMED Abstract]
  3. Altman AD, Bentley B, Murray S, et al.: Maternal age-related rates of gestational trophoblastic disease. Obstet Gynecol 112 (2 Pt 1): 244-50, 2008. [PUBMED Abstract]
  4. Gestational trophoblastic neoplasms. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 691-7.

Cellular Classification of Gestational Trophoblastic Disease

Gestational trophoblastic disease (GTD) may be classified as follows:[1]

Choriocarcinoma, PSTT, and ETT are often grouped under the heading gestational trophoblastic tumors.

Hydatidiform Mole (HM)

HM is defined as products of conception that show gross cyst-like swellings of the chorionic villi that are caused by an accumulation of fluid. There is disintegration and loss of blood vessels in the villous core.

Complete HM

A complete mole occurs when an ovum that has extruded its maternal nucleus is fertilized by either a single sperm, with subsequent chromosome duplication, or two sperm, resulting in either case in a diploid karyotype. The former case always yields a mole with a karyotype of 46 XX, since at least one X chromosome is required for viability and a karyotype of 46 YY is rapidly lethal to the ovum. The latter case may yield a karyotype of 46 XX or 46 XY. About 90% of complete HMs are 46 XX. On ultrasound examination, complete moles rarely reveal a fetus or amniotic fluid.

Partial HM

A partial mole occurs when the ovum retains its nucleus but is fertilized by a single sperm, with subsequent chromosome duplication, or is fertilized by two sperm; the possible resulting triploid karyotypes are 69 XXY, 69 XXX, or 69 XYY. Therefore, in contrast to a complete mole, the partial mole chromosomes of a partial mole are only two-thirds paternal in origin. In contrast to complete moles, partial moles usually show a fetus, which may even be viable, and amniotic fluid is visible.

Complete HMs have a 15% to 25% risk of developing into an invasive mole, but transformation to malignancy is much more rare (<5%) in the case of partial moles.

Gestational Trophoblastic Neoplasias

Invasive mole

Invasive moles (chorioadenoma destruens) are locally invasive, rarely metastatic lesions characterized microscopically by trophoblastic invasion of the myometrium with identifiable villous structures. These may be preceded by either complete or partial molar pregnancy. They are usually diploid in karyotype, but may be aneuploid. Microscopically, these lesions are characterized by hyperplasia of cytotrophoblastic and syncytial elements and persistence of villous structures. They may histologically resemble choriocarcinoma. Invasive moles have more aggressive behavior than either complete or partial HMs, and they are treated similarly to choriocarcinoma (i.e., with chemotherapy). However, unlike choriocarcinoma, they may regress spontaneously.

Choriocarcinoma

Choriocarcinoma is a malignant tumor of the trophoblastic epithelium. Uterine muscle and blood vessels are invaded with areas of hemorrhage and necrosis. Columns and sheets of trophoblastic tissue invade normal tissues and spread to distant sites, the most common of which are lungs, brain, liver, pelvis, vagina, spleen, intestines, and kidney. Most choriocarcinomas have an aneuploid karyotype, and about three-quarters of them contain a Y chromosome. Most follow an HM pregnancy, spontaneous abortion, or ectopic pregnancy; but, about one-quarter of them are preceded by a full-term pregnancy. Nearly all GTDs that are preceded by nonmolar pregnancies are choriocarcinomas; the rare exceptions generally are PSTTs.

PSTT

PSTT disease is the result of a very rare tumor arising from the placental implantation site and resembles an exaggerated form of syncytial endometritis. Trophoblastic cells infiltrate the myometrium, and there is vascular invasion. Human placental lactogen is present in the tumor cells, whereas immunoperoxidase staining for human chorionic gonadotropin (hCG) is positive in only scattered cells, and elevations in serum hCG are relatively low compared with the marked elevations seen in choriocarcinoma. hCG is not a reliable marker of tumor volume.[2,3] PSTTs have much lower growth rates than choriocarcinoma, and presentation after a full-term pregnancy is often delayed by months or years. They are generally resistant to chemotherapy. Therefore, hysterectomy is the standard primary treatment if the tumor is confined to the uterus. However, about 35% of PSTTs have distant metastases at diagnosis.[3,4] Common sites of metastasis include the lungs, pelvis, and lymph nodes. Central nervous system, renal, and liver metastases have also been observed.

ETT

ETT is an extremely rare gestational trophoblastic tumor.[5,6] Although this tumor was originally called an atypical choriocarcinoma, ETT appears to be less aggressive than choriocarcinoma and is now regarded as a distinct entity. Pathologically, it has a monomorphic cellular pattern of epithelioid cells and may resemble squamous cell cancer of the cervix when arising in the cervical canal. Its clinical behavior appears to be closer to that of PSTT than to choriocarcinoma. It has a spectrum of clinical behavior from benign to malignant. About one-third of patients present with metastases, usually in the lungs.

References
  1. Altieri A, Franceschi S, Ferlay J, et al.: Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol 4 (11): 670-8, 2003. [PUBMED Abstract]
  2. Lurain JR: Gestational trophoblastic tumors. Semin Surg Oncol 6 (6): 347-53, 1990. [PUBMED Abstract]
  3. Feltmate CM, Genest DR, Goldstein DP, et al.: Advances in the understanding of placental site trophoblastic tumor. J Reprod Med 47 (5): 337-41, 2002. [PUBMED Abstract]
  4. Schmid P, Nagai Y, Agarwal R, et al.: Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet 374 (9683): 48-55, 2009. [PUBMED Abstract]
  5. Shih IM, Kurman RJ: Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol 22 (11): 1393-403, 1998. [PUBMED Abstract]
  6. Palmer JE, Macdonald M, Wells M, et al.: Epithelioid trophoblastic tumor: a review of the literature. J Reprod Med 53 (7): 465-75, 2008. [PUBMED Abstract]

Stage Information for Gestational Trophoblastic Disease

Hydatidiform Mole (HM)

HM (molar pregnancy) is disease limited to the uterine cavity.

Gestational Trophoblastic Neoplasia

Definitions: FIGO

The Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging to define gestational trophoblastic neoplasia; the FIGO system is most commonly used.[1,2] Some tumor registrars encourage the recording of staging in both systems.

FIGO staging system (and modified World Health Organization [WHO] prognostic scoring system)

The FIGO staging system is as follows:[1]

Table 1. Gestational Trophoblastic Neoplasiaa,b
FIGO Anatomical Staging
FIGO = Fédération Internationale de Gynécologie et d’Obstétrique; hCG = human chorionic gonadotropin; WHO = World Health Organization.
aAdapted from FIGO Committee on Gynecologic Oncology.[1]
bTo stage and allot a risk factor score, a patient’s diagnosis is allocated to a stage as represented by a Roman numeral I, II, III, and IV. This is then separated by a colon from the sum of all the actual risk factor scores expressed in Arabic numerals, i.e., stage II:4, stage IV:9. This stage and score will be allotted for each patient.
cSize of the tumor in the uterus.
Stage
I Gestational trophoblastic tumors strictly confined to the uterine corpus.
II Gestational trophoblastic tumors extending to the adnexa or to the vagina, but limited to the genital structures.
III Gestational trophoblastic tumors extending to the lungs, with or without genital tract involvement.
IV All other metastatic sites.
Modified WHO Prognostic Scoring System as Adapted by FIGOb
Scores 0 1 2 4
Age <40 ≥40 – –
Antecedent pregnancy mole abortion term –
Interval months from index pregnancy <4 4–6 7–12 >12
Pretreatment serum hCG (IU/L) <103 103–104 104–105 >105
Largest tumor size (including uterusc) <3 3–4 cm ≥5 cm –
Site of metastases, including uterus lung spleen, kidney gastrointestinal tract liver, brain
Number of metastases – 1–4 5–8 >8
Previous failed chemotherapy – – single drug ≥2 drugs

In addition, the FIGO staging system incorporates a modified WHO prognostic scoring system. The scores from the eight risk factors are summed and incorporated into the FIGO stage, separated by a colon (e.g., stage II:4, stage IV:9, etc.). Unfortunately, a variety of risk scoring systems have been published, making comparisons of results difficult.

References
  1. Ngan HYS, Seckl MJ, Berkowitz RS, et al.: Diagnosis and management of gestational trophoblastic disease: 2021 update. Int J Gynaecol Obstet 155 (Suppl 1): 86-93, 2021. [PUBMED Abstract]
  2. Gestational trophoblastic neoplasms. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 691-7.

Treatment Option Overview for Gestational Trophoblastic Disease

Most hydatidiform moles (HMs) are benign and are treated conservatively by dilation, suction evacuation, and curettage. However, since they carry a risk of persistence or progression to malignant gestational trophoblastic disease (GTD), they must be followed carefully with weekly serum human chorionic gonadotropin (hCG) levels to normalization. Monthly follow-up for 6 months is generally recommended, although the duration of this phase of follow-up is not based on empiric study.[1]

Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. The modified World Health Organization (WHO) Prognostic Scoring System (see Table 1) should be used, and combination chemotherapy should be initiated when warranted by the patient’s score. If a diagnosis of GTD is made, routine work-up includes the following:

  • Serum beta-hCG.
  • Blood work of liver, renal, and marrow function.
  • Chest x-ray.
  • Pelvic ultrasound.
  • Head computed tomography or magnetic resonance imaging (in the case of choriocarcinoma or central nervous system signs).

Treatment of GTD depends on the risk category determined by the modified WHO Prognostic Scoring System as adapted by the Fédération Internationale de Gynécologie et d’Obstétrique (see Table 1). Since the very rare placental-site trophoblastic tumors and the even more rare epithelioid trophoblastic tumors are biologically distinct entities, their management is discussed separately.

Low Levels of hCG

Accurate monitoring of hCG is critical to successfully diagnose and monitor the treatment course of gestational trophoblastic disease. False-positive results may lead to inappropriate diagnoses and treatment, and must be minimized. The following are possible alternate diagnoses to be considered in cases of low-level hCG.

False-positive hCG

Serum hCG testing relies on detecting two antibodies on the hCG molecule. The antibodies are polyclonal or monoclonal antibodies derived from various animals: mouse, rabbit, goat or sheep. Humans with heterophilic (or cross-species) antibodies bind the antibodies in the assay, leading to a false-positive result. This was a common problem with one of the commercially available assays until it was re-engineered in 2003. Heterophilic antibodies cannot cross the glomerular filtration barrier, so the performance of a urinary hCG can eliminate this source for a positive test result. The urine sample should be run using the same system generally reserved for serum, as opposed to over-the-counter urine-pregnancy tests, to avoid decreased sensitivity in the latter.

Pituitary hCG

The anterior stalk of the pituitary secretes luteinizing hormone (LH), which shares an alpha subunit with hCG. In normal menstrual cycles, pituitary-generated hCG may be detectable at the time of the LH surge. Estrogen provides negative feedback for this LH secretion and acts as a suppressing agent. In patients in low-estrogen states (perimenopause, menopause, and status postoophorectomy), pituitary hCG may be secreted in increasing amounts, although only levels between 1 to 32 IU/L have been recorded.[2] To confirm a pituitary source for the hCG, patients are started on high-dose oral contraceptive pills to produce an exogenous source of estrogen. In general, patients with pituitary hCG will have their hCG levels suppressed after 3 weeks on this regimen.[2]

References
  1. Sita-Lumsden A, Short D, Lindsay I, et al.: Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000-2009. Br J Cancer 107 (11): 1810-4, 2012. [PUBMED Abstract]
  2. Muller CY, Cole LA: The quagmire of hCG and hCG testing in gynecologic oncology. Gynecol Oncol 112 (3): 663-72, 2009. [PUBMED Abstract]

Management of Hydatidiform Mole

Treatment of hydatidiform mole (HM) is within the purview of the obstetrician/gynecologist and is not discussed separately here. However, following the diagnosis and treatment of HM, patients should be monitored to rule out the possibility of metastatic gestational trophoblastic neoplasia. In almost all cases, this can be performed with routine monitoring of serum beta human chorionic gonadotropin (beta-hCG) to document its return to normal. An effective form of contraception is important during the follow-up period to avoid the confusion that can occur with a rising beta-hCG as a result of pregnancy.

Chemotherapy is necessary when there is the following:

  1. A rising beta-hCG titer for 2 weeks (3 titers).
  2. A tissue diagnosis of choriocarcinoma.
  3. A plateau of the beta-hCG for 3 weeks.
  4. Persistence of detectable beta-hCG 6 months after mole evacuation.
  5. Metastatic disease.
  6. An elevation in beta-hCG after a normal value.
  7. Postevacuation hemorrhage not caused by retained tissues.

Chemotherapy is ultimately required for persistence or neoplastic transformation in about 15% to 20% of patients after evacuation of a complete HM but for fewer than 5% of patients with partial HM. Chemotherapy is determined by the patient’s modified World Health Organization score.

In women with complete HM, risk of persistence or neoplastic transformation is approximately doubled in the setting of certain characteristics, which include the following:

  • Age older than 35 years or younger than 20 years.
  • Pre-evacuation serum beta-hCG greater than 100,000 IU/L.
  • Large-for-date uterus.
  • Large uterine molar mass.
  • Large (>6 cm) ovarian cysts.
  • Preeclampsia.
  • Hyperthyroidism.
  • Hyperemesis of pregnancy.
  • Trophoblastic embolization.
  • Disseminated intravascular coagulation.

Studies have shown that a single course of prophylactic dactinomycin or methotrexate can decrease the risk of a postmolar gestational trophoblastic disease (GTD).[1–3] However, there is concern that chemoprophylaxis increases tumor resistance to standard therapy in the women who subsequently develop GTD.[1] Therefore, this practice is generally limited to countries in which a large number of women do not return for follow-up.

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. Kim DS, Moon H, Kim KT, et al.: Effects of prophylactic chemotherapy for persistent trophoblastic disease in patients with complete hydatidiform mole. Obstet Gynecol 67 (5): 690-4, 1986. [PUBMED Abstract]
  2. Limpongsanurak S: Prophylactic actinomycin D for high-risk complete hydatidiform mole. J Reprod Med 46 (2): 110-6, 2001. [PUBMED Abstract]
  3. Uberti EM, Fajardo Mdo C, Ferreira SV, et al.: Reproductive outcome after discharge of patients with high-risk hydatidiform mole with or without use of one bolus dose of actinomycin D, as prophylactic chemotherapy, during the uterine evacuation of molar pregnancy. Gynecol Oncol 115 (3): 476-81, 2009. [PUBMED Abstract]

Treatment of Low-Risk Gestational Trophoblastic Neoplasia (FIGO Score 0–6)

There is no consensus on the best chemotherapy regimen for initial management of low-risk gestational trophoblastic neoplasia (GTN), and first-line regimens vary by geography and institutional preference. Most regimens have not been compared head-to-head, and the level of evidence for efficacy is often limited to C2 except as noted below. Even if there are differences in initial remission rate among the regimens, salvage with alternate regimens is very effective, and the ultimate cure rates are generally 99% or more. The initial regimen is generally given until a normal beta human chorionic gonadotropin (beta-hCG) (for the institution) is achieved and sustained for 3 consecutive weeks (or at least for one treatment cycle beyond normalization of the beta-hCG). A salvage regimen is instituted if any of the following occur:

  • A plateau of the beta-hCG for 3 weeks (defined as a beta-hCG decrease of 10% or less for 3 consecutive weeks).
  • A rise in beta-hCG of greater than 20% for 2 consecutive weeks.
  • Appearance of metastases.

The use of chemotherapy in the first-line management of low-risk GTN has been assessed in a Cochrane Collaboration systematic review.[1] In that systematic review, four randomized controlled trials were identified.[2–5]

Three of the randomized trials [3–5] compared the same two commonly used regimens:

  • Biweekly (pulsed) dactinomycin (1.25 mg/m2 intravenously [IV]).
  • Weekly intramuscular (IM) methotrexate (30 mg/m2).

These three trials included a total of 392 patients. In all three trials, patients who received pulsed dactinomycin had better primary complete response rates without the need for additional salvage therapy (relative risk [RR] of cure, 3.00; 95% confidence interval [CI], 1.10–8.17), even though the magnitude of benefit showed substantial heterogeneity (I2 statistic = 79%).[3–5][Level of evidence B1] Fewer courses of dactinomycin therapy were needed to achieve complete response and cure. As expected, salvage chemotherapy was nearly uniformly successful, because almost all low-risk GTN patients are ultimately cured, irrespective of the initial chemotherapeutic regimen. There were no statistically significant differences in most toxicities, including the following:

  • Nausea and vomiting.
  • Diarrhea.
  • Hematologic toxicity.
  • Hepatic toxicity.

There was a statistically significant increase in dermatologic toxicity, including alopecia, associated with dactinomycin. However, in the largest study,[5] there was more low-grade gastrointestinal toxicity, grade 2 nausea, grade 1 to 2 vomiting, and grades 1 to 3 neutropenia in the dactinomycin group. These values were statistically significant. In this study, patients with choriocarcinoma and risk scores of 5 to 6 had worse complete response rates to initial treatment with single-agent therapy. Methotrexate was virtually ineffective.[5]

The fourth randomized trial was very small and included 45 patients. The study compared a 5-day regimen of dactinomycin (10 μg/kg) with an 8-day regimen of methotrexate (1 mg/kg) and leucovorin (0.1 mg/kg) on alternate days. There was a statistically significant decrease in risk of failure to achieve primary cure without the need for salvage therapy in the dactinomycin arm (RR, 0.57; 95% CI, 0.40–0.81).[2][Level of evidence B1] There was less alopecia associated with methotrexate but more hepatic toxicity.

The Cochrane systematic review also summarized the evidence from four nonrandomized trials, but comparisons across studies are difficult. The regimens evaluated in those studies are included in the lists below.[1][Level of evidence C2]

Commonly used treatment regimens include the following:

  1. The 8-day Charing Cross regimen. Methotrexate (50 mg IM on days 1, 3, 5, and 7) and leucovorin (7.5 mg orally on days 2, 4, 6, and 8). This may be the most common regimen worldwide,[1,6] but it has not been directly compared with other regimens.
  2. Biweekly pulsed dactinomycin (1.25 mg/m2 IV).
  3. Weekly methotrexate (30 mg/m2 IM). Efficacy of this regimen appears to be low for choriocarcinoma and for patients with Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) risk scores of 5 to 6.

Other regimens in less-common use include the following:[1]

  • An 8-day regimen of methotrexate (1 mg/kg IM on days 1, 3, 5, and 7) and leucovorin (0.1 mg/kg IM on days 2, 4, 6, and 8).
  • Methotrexate 20 mg/m2 IM on days 1 to 5, repeated every 14 days.
  • Dactinomycin 12 μg/kg/day IV on days 1 to 5, repeated every 2 to 3 weeks. This regimen is used less often because of substantial alopecia and nausea.
  • Methotrexate 20 mg IM daily on days 1 to 5; and dactinomycin 500 μg IV daily on days 1 to 5, repeated every 14 days.
  • Dactinomycin 10 μg/kg/day on days 1 to 5, repeated every 2 weeks.
  • Methotrexate 0.4 mg/kg/day IM daily on days 1 to 5, repeated after 7 days.
  • Etoposide 100 mg/m2/day IV on days 1 to 5, or 250 mg/m2 IV on days 1 and 3, at 10-day intervals.[7]

The unusual patient with a tumor that becomes refractory to single-agent chemotherapy is treated with one of the combination regimens described below for high-risk GTN. For more information, see the Treatment of High-Risk Gestational Trophoblastic Neoplasia (FIGO Score ≥7) section.

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. Alazzam M, Tidy J, Hancock BW, et al.: First line chemotherapy in low risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev (1): CD007102, 2009. [PUBMED Abstract]
  2. Lertkhachonsuk AA, Israngura N, Wilailak S, et al.: Actinomycin d versus methotrexate-folinic acid as the treatment of stage I, low-risk gestational trophoblastic neoplasia: a randomized controlled trial. Int J Gynecol Cancer 19 (5): 985-8, 2009. [PUBMED Abstract]
  3. Gilani MM, Yarandi F, Eftekhar Z, et al.: Comparison of pulse methotrexate and pulse dactinomycin in the treatment of low-risk gestational trophoblastic neoplasia. Aust N Z J Obstet Gynaecol 45 (2): 161-4, 2005. [PUBMED Abstract]
  4. Yarandi F, Eftekhar Z, Shojaei H, et al.: Pulse methotrexate versus pulse actinomycin D in the treatment of low-risk gestational trophoblastic neoplasia. Int J Gynaecol Obstet 103 (1): 33-7, 2008. [PUBMED Abstract]
  5. Osborne RJ, Filiaci V, Schink JC, et al.: Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study. J Clin Oncol 29 (7): 825-31, 2011. [PUBMED Abstract]
  6. Khan F, Everard J, Ahmed S, et al.: Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects. Br J Cancer 89 (12): 2197-201, 2003. [PUBMED Abstract]
  7. Hitchins RN, Holden L, Newlands ES, et al.: Single agent etoposide in gestational trophoblastic tumours. Experience at Charing Cross Hospital 1978-1987. Eur J Cancer Clin Oncol 24 (6): 1041-6, 1988. [PUBMED Abstract]

Treatment of High-Risk Gestational Trophoblastic Neoplasia (FIGO Score ≥7)

Multiagent chemotherapy is standard for the initial management of high-risk gestational trophoblastic neoplasia (GTN). A systematic literature review revealed only one randomized controlled trial (and no high-quality trials)—conducted in the 1980s—comparing multiagent chemotherapy regimens for high-risk GTN.[1] In the trial, only 42 women were randomly assigned to either a CHAMOMA regimen (i.e., methotrexate, leucovorin, hydroxyurea, dactinomycin, vincristine, melphalan, and doxorubicin) or MAC (i.e., methotrexate, dactinomycin, and chlorambucil).[2] There was substantially more life-threatening toxicity in the CHAMOMA arm and no evidence of higher efficacy. However, there were serious methodological problems with this trial. It was reportedly designed as an equivalency trial, but owing to the small sample size, the trial was inadequately powered to assess equivalence. In addition, the characteristics of the patients randomly assigned to the two study arms were not reported (although the authors stated that there were no major differences in the patient populations assigned to each arm), nor was the method of randomization or allocation concealment described.

There are no randomized trials comparing regimens in common use to establish the superiority of one over another. Therefore, the literature does not permit firm conclusions about the best chemotherapeutic regimen.[1][Level of evidence C2] However, since EMA/CO (i.e., etoposide, methotrexate, and dactinomycin/cyclophosphamide and vincristine) is the most commonly used regimen, the specifics are provided in Table 2 below.[3–5]

Table 2. Specifics of the EMA/CO Regimena,b,c
Day Drug Dose
IV = intravenously; PO = orally.
aAdapted from Bower et al.[3]
bAdapted from Escobar et al.[4]
cAdapted from Lurain et al.[5]
1 Etoposide 100 mg/m2 IV for 30 min
  Dactinomycin 0.5 mg IV push
  Methotrexate 300 mg/m2 IV for 12 h
2 Etoposide 100 mg/m2 IV for 30 min
  Dactinomycin 0.5 mg IV push
  Leucovorin 15 mg or PO every 12 h × 4 doses, beginning 24 h after the start of methotrexate
8 Cyclophosphamide 600 mg/m2 IV infusion
  Vincristine 0.8–1.0 mg/m2 IV push (maximum dose 2 mg)

Cycles are repeated every 2 weeks (on days 15, 16, and 22) until any metastases present at diagnosis disappear and serum beta-human chorionic gonadotropin (beta-hCG) has normalized, then the treatment is usually continued for an additional three to four cycles.

Results of a large, consecutive case series of 272 patients with up to 16 years of follow-up showed a complete remission rate of 78% using this regimen, and these results are consistent with other case series in the literature that employed EMA/CO.[3] More than two-thirds of the women who did not have a complete response or subsequently had disease recurrence could be salvaged with cisplatin-containing regimens (with or without resection of metastases), yielding a long-term cure rate of 86.2% (95% confidence interval, 81.9%–90.5%).[3][Level of evidence C1] Moreover, routinely when the addition of cisplatin plus etoposide was added to EMA/CO, a 9% improvement was reported in the survival results of these high-risk patients.[6] Among the women who had an intact uterus, about 50% retained their fertility. Patients with documented brain metastases received higher doses of systemic methotrexate as part of the EMA component of EMA/CO (1 g/m2 intravenously [IV] for 24 hours, followed by leucovorin rescue, 15 mg orally every 6 hours for 12 doses starting 32 hours after methotrexate). Patients with brain metastases received an increased dose of systemic methotrexate of 1 g/m2 for 24 hours followed by leucovorin (15 mg orally every 6 hours for 12 doses starting 32 hours after methotrexate). Patients with lung metastases received cranial prophylaxis with irradiation and intrathecal methotrexate 12.5 mg every 2 weeks with the CO (i.e., cyclophosphamide and vincristine) cycles.

Examples of other regimens that have been used include the following:[1]

  • MAC: Methotrexate, leucovorin, dactinomycin, and cyclophosphamide.
  • Another MAC: Methotrexate, dactinomycin, and chlorambucil.
  • EMA: Etoposide, methotrexate, leucovorin, and dactinomycin (EMA/CO without the CO).
  • CHAMOCA: Methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine.
  • CHAMOMA: Methotrexate, leucovorin, hydroxyurea, dactinomycin, vincristine, melphalan, and doxorubicin.

Brain metastases are associated with poor prognosis, particularly when liver metastases are also present.[7–9] However, even patients with brain metastases may achieve long-term remission in 50% to 80% of cases.[3,4,9] Patients with central nervous system (CNS) metastases receive additional therapy simultaneously with the initiation of systemic chemotherapy. Some centers use whole-brain irradiation (30 Gy in 2 Gy fractions) with or without intrathecal methotrexate.[7] However, some investigators omit the cranial radiation, relying on replacement of the standard dose of methotrexate in the EMA/CO regimen with the higher dose of 1,000 mg/m2 IV for 24 hours on the first day, as noted above, to achieve therapeutic CNS levels.[9]

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. Deng L, Yan X, Zhang J, et al.: Combination chemotherapy for high-risk gestational trophoblastic tumour. Cochrane Database Syst Rev (2): CD005196, 2009. [PUBMED Abstract]
  2. Curry SL, Blessing JA, DiSaia PJ, et al.: A prospective randomized comparison of methotrexate, dactinomycin, and chlorambucil versus methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine in “poor prognosis” metastatic gestational trophoblastic disease: a Gynecologic Oncology Group study. Obstet Gynecol 73 (3 Pt 1): 357-62, 1989. [PUBMED Abstract]
  3. Bower M, Newlands ES, Holden L, et al.: EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients. J Clin Oncol 15 (7): 2636-43, 1997. [PUBMED Abstract]
  4. Escobar PF, Lurain JR, Singh DK, et al.: Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy. Gynecol Oncol 91 (3): 552-7, 2003. [PUBMED Abstract]
  5. Lurain JR, Singh DK, Schink JC: Management of metastatic high-risk gestational trophoblastic neoplasia: FIGO stages II-IV: risk factor score > or = 7. J Reprod Med 55 (5-6): 199-207, 2010 May-Jun. [PUBMED Abstract]
  6. Alifrangis C, Agarwal R, Short D, et al.: EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis. J Clin Oncol 31 (2): 280-6, 2013. [PUBMED Abstract]
  7. Small W, Lurain JR, Shetty RM, et al.: Gestational trophoblastic disease metastatic to the brain. Radiology 200 (1): 277-80, 1996. [PUBMED Abstract]
  8. Crawford RA, Newlands E, Rustin GJ, et al.: Gestational trophoblastic disease with liver metastases: the Charing Cross experience. Br J Obstet Gynaecol 104 (1): 105-9, 1997. [PUBMED Abstract]
  9. Newlands ES, Holden L, Seckl MJ, et al.: Management of brain metastases in patients with high-risk gestational trophoblastic tumors. J Reprod Med 47 (6): 465-71, 2002. [PUBMED Abstract]

Treatment of Placental-Site Trophoblastic Tumor

Because placental-site trophoblastic tumors (PSTTs) are rare, reports of therapeutic results are confined to relatively small case series with accrual extending for very long time periods. Therefore, few reliable comparisons among surgical approaches or chemotherapeutic regimens can be made. Nevertheless, there are distinctions in underlying biology between PSTTs and the other gestational trophoblastic tumors—particularly resistance to chemotherapy—that justify specific treatment strategies, such as the following:

  1. Tumors confined to the uterus (Fédération Internationale de Gynécologie et d’Obstétrique [FIGO] Stage I).

    Hysterectomy is the treatment of choice.[1,2] In a relatively large, retrospective, population-based, consecutive case series of 62 women with PSTT, 33 had disease confined to the uterus and were treated with hysterectomy (n = 17) or with hysterectomy plus chemotherapy (n = 16). Overall survival rates at 10 years were virtually identical between the two groups (90% and 91%, respectively). There was only one recurrence in the surgery group and two in the combination therapy group.[2][Level of evidence C2] There is little evidence to guide the optimal extent of surgery (e.g., lymph node resection or oophorectomy).

  2. Tumors with extrauterine spread to genital structures (FIGO stage II).

    Complete resection with or without adjuvant chemotherapy. Because the relapse rate is high after surgery and overall mortality in patients is high, adjuvant multiple-agent chemotherapy should be considered.[1,2][Level of evidence C2] However, the impact of adjuvant therapy on overall mortality is uncertain.

  3. Metastatic tumors (FIGO stages III and IV).

    Polyagent chemotherapy. A variety of regimens have been used with no direct comparisons to determine whether one is superior. Some of the regimens include the following:[1,2]

    • EMA/CO: Etoposide, methotrexate with leucovorin rescue, dactinomycin, cyclophosphamide, and vincristine. This appears to be the most commonly used regimen.
    • EP/EMA: Etoposide and cisplatin with etoposide, methotrexate, and dactinomycin.
    • MAE: Methotrexate with leucovorin rescue, dactinomycin, and etoposide.

In part because of the inherent chemoresistance of PSTTs, resection of tumors is often considered in addition to chemotherapy regimens used for high-risk gestational trophoblastic neoplasias. In retrospective series, adjuvant surgery, such as hysterectomy, excision of lung metastases, or removal of obstructing abdominal lesions, has been associated with favorable disease control. However, it is not clear which component of the favorable outcomes is attributable to the surgery or to patient selection factors.[2,3][Level of evidence C2]

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. Lurain JR: Gestational trophoblastic tumors. Semin Surg Oncol 6 (6): 347-53, 1990. [PUBMED Abstract]
  2. Schmid P, Nagai Y, Agarwal R, et al.: Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet 374 (9683): 48-55, 2009. [PUBMED Abstract]
  3. Feltmate CM, Genest DR, Goldstein DP, et al.: Advances in the understanding of placental site trophoblastic tumor. J Reprod Med 47 (5): 337-41, 2002. [PUBMED Abstract]

Treatment of Epithelioid Trophoblastic Tumor

Epithelioid trophoblastic tumors (ETTs) are exceedingly rare, and there is little information to guide therapy. However, these tumors are similar in behavior and prognosis to placental-site trophoblastic tumors, so it is reasonable to manage them similarly. For more information, see the Treatment of Placental-Site Trophoblastic Tumor section. Few ETTs are malignant in nature, but they are not very responsive to systemic therapy. A variety of chemotherapy regimens have been used.[1]

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. Palmer JE, Macdonald M, Wells M, et al.: Epithelioid trophoblastic tumor: a review of the literature. J Reprod Med 53 (7): 465-75, 2008. [PUBMED Abstract]

Treatment of Recurrent or Chemoresistant Gestational Trophoblastic Neoplasia

Recurrent disease indicates failure of prior chemotherapy unless initial therapy was surgery alone. One study found recurrence of disease in 2.5% of patients with nonmetastatic disease, 3.7% of patients with good-prognosis metastatic disease, and 13% of patients with poor-prognosis metastatic disease.[1] Nearly all recurrences occur within 3 years of remission (85% before 18 months). A patient whose disease progresses after primary surgical therapy is generally treated with single-agent chemotherapy unless one of the poor-prognosis factors that requires combination chemotherapy supervenes. Relapse after failure of prior chemotherapy automatically places the patient in the high-risk category. These patients should be treated with aggressive chemotherapy.

Reports of combination chemotherapy come from small retrospective case series. Long-term disease-free survival, in excess of 50%, is achievable with combination drug regimens.[2][Level of evidence C2] A variety of regimens have been reported that include combinations of the following:[3–7]

  • Cisplatin.
  • Etoposide.
  • Bleomycin.
  • Ifosfamide.
  • Paclitaxel.
  • Fluorouracil.
  • Floxuridine.

A select group of patients with chemotherapy-resistant and clinically detectable gestational trophoblastic neoplasia may benefit from salvage surgery.[8][Level of evidence C2]

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.[9,10] 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.[9–11] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient’s DPYD genotype and number of functioning DPYD alleles.[12–14] DPYD genetic testing costs less than $200, but insurance coverage varies due to a lack of national guidelines.[15] In addition, testing may delay therapy by 2 weeks, which would not be advisable in urgent situations. This controversial issue requires further evaluation.[16]

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. Mutch DG, Soper JT, Babcock CJ, et al.: Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center. Cancer 66 (5): 978-82, 1990. [PUBMED Abstract]
  2. Newlands ES: The management of recurrent and drug-resistant gestational trophoblastic neoplasia (GTN). Best Pract Res Clin Obstet Gynaecol 17 (6): 905-23, 2003. [PUBMED Abstract]
  3. Matsui H, Iitsuka Y, Suzuka K, et al.: Salvage chemotherapy for high-risk gestational trophoblastic tumor. J Reprod Med 49 (6): 438-42, 2004. [PUBMED Abstract]
  4. Xiang Y, Sun Z, Wan X, et al.: EMA/EP chemotherapy for chemorefractory gestational trophoblastic tumor. J Reprod Med 49 (6): 443-6, 2004. [PUBMED Abstract]
  5. Lurain JR, Nejad B: Secondary chemotherapy for high-risk gestational trophoblastic neoplasia. Gynecol Oncol 97 (2): 618-23, 2005. [PUBMED Abstract]
  6. Wan X, Xiang Y, Yang X, et al.: Efficacy of the FAEV regimen in the treatment of high-risk, drug-resistant gestational trophoblastic tumor. J Reprod Med 52 (10): 941-4, 2007. [PUBMED Abstract]
  7. Wang J, Short D, Sebire NJ, et al.: Salvage chemotherapy of relapsed or high-risk gestational trophoblastic neoplasia (GTN) with paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE). Ann Oncol 19 (9): 1578-83, 2008. [PUBMED Abstract]
  8. Lehman E, Gershenson DM, Burke TW, et al.: Salvage surgery for chemorefractory gestational trophoblastic disease. J Clin Oncol 12 (12): 2737-42, 1994. [PUBMED Abstract]
  9. 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]
  10. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. 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]

Latest Updates to This Summary (07/19/2024)

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.

Treatment of Recurrent or Chemoresistant Gestational Trophoblastic Neoplasia

Added Fluorouracil Dosing as a new subsection.

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 gestational trophoblastic disease. 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:

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  • be cited with text, or
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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.

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.

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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 Gestational Trophoblastic Disease Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: /types/gestational-trophoblastic/hp/gtd-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389414]

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Gestational Trophoblastic Disease—Health Professional Version

Gestational Trophoblastic Disease—Health Professional Version

Treatment

PDQ Treatment Information for Health Professionals

More information

Causes & Prevention

NCI does not have PDQ evidence-based information about prevention of gestational trophoblastic disease.

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Screening

NCI does not have PDQ evidence-based information about screening for gestational trophoblastic disease.

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Supportive & Palliative Care

We offer evidence-based supportive and palliative care information for health professionals on the assessment and management of cancer-related symptoms and conditions.

Cancer Pain Nausea and Vomiting Nutrition in Cancer Care Transition to End-of-Life Care Last Days of Life View all Supportive and Palliative Care Summaries

Gestational Trophoblastic Disease—Patient Version

Gestational Trophoblastic Disease—Patient Version

Overview

Gestational trophoblastic disease (GTD) is a general term for rare tumors that form from the tissues surrounding fertilized egg. GTD is often found early and usually cured. Hydatidiform mole (HM) is the most common type of GTD. Explore the links on this page to learn more about GTD treatment and clinical trials.

Treatment

PDQ Treatment Information for Patients

More information

Causes & Prevention

NCI does not have PDQ evidence-based information about prevention of gestational trophoblastic disease.

More information

Screening

NCI does not have PDQ evidence-based information about screening for gestational trophoblastic disease.

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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

Stomach Cancer Survival Rates and Prognosis

Photo of a doctor sitting at a desk speaking with a patient.

Your doctor can discuss your prognosis–the likely outcome of your cancer–with you. Some people like to have a loved one or friend with them for the conversation. 

Credit: iStock

If you’ve been diagnosed with stomach cancer, you may have questions about how serious the cancer is and your chances of survival. The likely outcome or course of a disease is called prognosis.     

The prognosis for stomach cancer depends on

  • the stage of the cancer, including whether the cancer is only in the stomach or has spread to lymph nodes or other places in the body 
  • your overall health  

When stomach cancer is found early, there is a better chance of recovery. Stomach cancer is often advanced when it is diagnosed. At advanced stages, stomach cancer can be treated but is rarely cured. Learn more about Stomach Cancer Treatment.

Survival rates for stomach cancer

Doctors estimate stomach cancer prognosis by using statistics collected over many years from people with stomach cancer. One statistic that is commonly used in making a prognosis is the 5-year relative survival rate. The 5-year relative survival rate tells you what percent of people with the same type and stage of stomach cancer are alive 5 years after their cancer was diagnosed, compared with people in the overall population. For example, the 5-year relative survival rate for stomach cancer is 36%. This means that, overall, people diagnosed with stomach cancer are 36% as likely as similar people who do not have stomach cancer to be alive 5 years after diagnosis.

Stomach Cancer Statistics

Learn more about statistics for stomach cancer from our Cancer Stat Facts Collection, including new cases, survival rates, and who is most affected.

The 5-year relative survival rates for different stages of stomach cancer are:

  • 75% for localized stomach cancer (cancer is in the stomach only)
  • 35% for regional stomach cancer (cancer has spread beyond the stomach to nearby lymph nodes or organs)
  • 7% for metastatic stomach cancer (cancer has spread beyond the stomach to a distant part of the body)

Understanding survival rate statistics

Because survival statistics are based on large groups of people, they cannot be used to predict exactly what will happen to you. The doctor who knows the most about your situation is in the best position to discuss these statistics and talk with you about your prognosis. It is important to note the following when reviewing survival statistics:    

  • No two people are alike, and responses to treatment can vary greatly.
  • Survival statistics use information collected from large groups of people who may have received different types of treatment.
  • It takes several years to see the effect of newer and better treatments, so current survival statistics may not reflect newer treatments.

To learn more about survival statistics and to see videos of patients and their doctors exploring their feelings about prognosis see Understanding Cancer Prognosis.  

Coping with Stomach Cancer

Photo of a woman in head covering sitting and meeting with her doctor.

It’s important to talk with your health care provider about side effects you are experiencing and any concerns you have.

Credit: iStock

Stomach cancer and its treatments may cause physical and emotional side effects. When you first learn that you have stomach cancer, you may wonder how you’re going to cope with the upcoming changes in your life. One step you can take is to be informed of the changes that may occur and what resources are available to help you. Speaking up about any problems you have can give you a greater sense of control. Your health care team can talk with you about ways to reduce these side effects so you feel better.   

For resources on the common physical side effects of treatment for stomach cancer, see Stomach Cancer Treatment. Learn more about side effects of cancer treatment and ways to manage them. For help with emotional side effects, see Emotions and Cancer.

Changes in eating and nutrition

Stomach cancer and its treatments may affect your ability to eat enough food or absorb the nutrients from food. If part or all of your stomach has been removed, you might need to eat smaller amounts of food more often or make changes to what you eat. Your doctor or dietitian may recommend that you stay upright for some time after eating. They can also help you adjust your diet to make sure you get the nutrition you need.  

To get tips on eating during cancer treatment, see Eating Hints: Before, during, and after Cancer Treatment.  

Learn more about how cancer affects nutrition in Nutrition in Cancer Care.   

Changes in body image

Stomach cancer and its treatment can change how you look and feel about yourself. Know that you aren’t alone in how you feel.  Coping with changes to your body and the way you see yourself can be hard. But, over time, many people learn to adjust and move forward.

Learn more about how body changes may affect your self-image and sex life after treatment and ways to cope and communicate your feelings in How Cancer Affects Your Self-Image and Sexuality.

Stress in dealing with follow-up care

Life After Cancer Treatment

Adjusting to physical and emotional changes after cancer treatment and coping with fear of recurrence as a cancer survivor.

Many people who have been treated for stomach cancer need to visit their doctor regularly to get follow-up exams or tests. Planning and scheduling these appointments can be stressful and time-consuming. Waiting for test results can cause anxiety and an ongoing fear of recurrence. The added costs of things such as copays, medicines, and parking and transportation fees only add to the stress. For tips on how to deal with the fear of cancer coming back, see the section Coping with Fear of Recurrence on our A New Normal page.

Cost of cancer treatment

Managing Cancer Costs and Medical Information

Learn ways to manage health care information, bills, and other records, along with tips for saving money on pain medicines.

Cancer is one of the most costly diseases to treat in the United States. Even if you have health insurance, you may face major financial challenges and need help dealing with the costs of stomach cancer treatment. The problems a person has related to the cost of treatment is known as financial toxicity. For tips and ways to cope, see Managing Cancer Costs and Medical Information. To learn about financial toxicity and find out if you are at risk, see Financial Toxicity (Financial Distress) and Cancer Treatment.

Stomach Cancer Stages

Cancer stage describes the extent of cancer in the body, such as the size of the tumor, whether it has spread, and how far it has spread from where it first formed. It is important to know the stage of the stomach cancer to plan the best treatment.   

There are several staging systems for cancer that describe the extent of the cancer. Stomach cancer staging usually uses the TNM staging system. You may see your cancer described by this staging system in your pathology report. Based on the TNM results, a stage (I, II, III, or IV, also written as 1, 2, 3, or 4) is assigned to your cancer. When talking to you about your cancer, your doctor may describe it as one of these stages.   

For information about how doctors stage stomach cancer, see the tests to stage stomach cancer section on Stomach Cancer Diagnosis. Learn more about Cancer Staging.  

The information on this page is about staging for adenocarcinoma of the stomach, the most common type of stomach cancer. 

Layers of the stomach wall 

The stomach wall is made up of five layers of tissue and muscle. Knowing about these layers can help you understand the stage of your cancer.

Layers of the stomach wall; drawing of the stomach with an inset showing the layers of the stomach wall, including the mucosa (innermost layer), submucosa, muscle layer, subserosa, and serosa (outermost layer).

Layers of the stomach wall. The wall of the stomach is made up of the mucosa (innermost layer), submucosa, muscle layer, subserosa, and serosa (outermost layer). The stomach is an organ in the upper abdomen.

Credit: © Terese Winslow

Enlarge Image

  • The mucosa is the innermost layer of the stomach wall. It is made of both epithelial cells and glandular cells. The glandular cells make mucus to protect the stomach lining and digestive juices to help break down food. Most stomach cancers start in glandular cells of the mucosa. Cancers that start in glandular cells are adenocarcinomas.   
  • The submucosa is the layer of connective tissue between the mucosa and the muscle layer. It contains blood vessels, lymph vessels, and nerve cells.  
  • The muscle layer is the next layer. The muscle layer helps the stomach mix food with digestive juices and move it into the small intestine, where nutrients are absorbed.  
  • The subserosa is a thin layer of connective tissue between the muscle layer and the serosa.  
  • The serosa is the outermost layer of the stomach wall.  

Stomach cancers become more advanced as they spread from the mucosa to the outer layers.  

To learn more about the stomach, see What Is Stomach Cancer?  

Stage 0 (carcinoma in situ) of the stomach

Stage 0 refers to carcinoma in situ. This means that abnormal cells are found in the mucosa. These abnormal cells may become cancer and spread into nearby normal tissue.   

Learn about treatment of stage 0 (carcinoma in situ) of the stomach. 

Stage I (also called stage 1) stomach cancer

Stage I  is divided into stages IA and IB.  

  • In stage IA,  
    • cancer has formed in the mucosa and may have spread to the submucosa.
  • In stage IB,  
    • cancer has formed in the mucosa and may have spread to the submucosa and has spread to 1 or 2 nearby lymph nodes; or
    • cancer has formed in the mucosa and has spread to the muscle layer.

Learn about treatment of stage I stomach cancer.  

Stage II (also called stage 2) stomach cancer

Stage II is divided into stages IIA and IIB.  

  • In stage IIA,  
    • cancer may have spread to the submucosa and has spread to 3 to 6 nearby lymph nodes; or  
    • cancer has spread to the muscle layer and to 1 or 2 nearby lymph nodes; or  
    • cancer has spread to the subserosa.
  • In stage IIB,  
    • cancer may have spread to the submucosa and has spread to 7 to 15 nearby lymph nodes; or  
    • cancer has spread to the muscle layer and to 3 to 6 nearby lymph nodes; or  
    • cancer has spread to the subserosa and to 1 or 2 nearby lymph nodes; or  
    • cancer has spread to the serosa.

Learn about treatment of stage II stomach cancer.  

Stage III (also called stage 3) stomach cancer

Stage III is divided into stages IIIA, IIIB, and IIIC.  

  • In stage IIIA,  
    • cancer has spread to the muscle layer and to 7 to 15 nearby lymph nodes; or
    • cancer has spread to the subserosa and to 3 to 6 nearby lymph nodes; or
    • cancer has spread to the serosa and to 1 to 6 nearby lymph nodes; or
    • cancer has spread to nearby organs, such as the spleen, colon, liver, diaphragm, pancreas, abdomen wall, adrenal gland, kidney, or small intestine, or to the back of the abdomen.
  • In stage IIIB,  
    • cancer may have spread to the submucosa or to the muscle layer and has spread to 16 or more nearby lymph nodes; or  
    • cancer has spread to the subserosa or to the serosa and has spread to 7 to 15 nearby lymph nodes; or  
    • cancer has spread to nearby organs, such as the spleen, colon, liver, diaphragm, pancreas, abdomen wall, adrenal gland, kidney, or small intestine, or to the back of the abdomen. Cancer has also spread to 1 to 6 nearby lymph nodes.  
  • In stage IIIC,  
    • cancer has spread to the subserosa or to the serosa, and to 16 or more nearby lymph nodes; or
    • cancer has spread to nearby organs, such as the spleen, colon, liver, diaphragm, pancreas, abdomen wall, adrenal gland, kidney, or small intestine, or to the back of the abdomen. Cancer also has spread to 7 or more nearby lymph nodes.

Learn about treatment of stage III stomach cancer.

Stage IV (also called stage 4) stomach cancer

In stage IV, cancer has spread to other parts of the body, such as the lungs, liver, distant lymph nodes, and the tissue that lines the abdomen wall.

Stage IV stomach cancer is also called metastatic stomach cancer. Metastatic cancer happens when cancer cells travel through the lymphatic system or blood and form tumors in other parts of the body. The metastatic tumor is the same type of cancer as the primary tumor. For example, if stomach cancer spreads to the lung, the cancer cells in the lung are actually stomach cancer cells. The disease is called metastatic stomach cancer, not lung cancer. Learn more in Metastatic Cancer: When Cancer Spreads.

Learn about treatment of stage IV stomach cancer.

Recurrent stomach cancer

Recurrent stomach cancer is cancer that has recurred (come back) after it has been treated. Stomach cancer may come back in the stomach, lymph nodes, or other parts of the body, such as the liver, lung, or bone. Tests will be done to help determine where the cancer has returned in your body. The type of treatment that you have for recurrent stomach cancer will depend on where it has come back.  

Learn more in Recurrent Cancer: When Cancer Comes Back. Information to help you cope and talk with your health care team can be found in Coping with Stomach Cancer.

Learn about treatment of recurrent stomach cancer. 

Stomach Cancer Treatment

Different types of treatments are available for stomach cancer. You and your cancer care team will work together to decide your treatment plan, which may include more than one type of treatment. Many factors will be considered, such as the stage of the cancer, your overall health, and your preferences. Your plan will include information about your cancer, the goals of treatment, your treatment options and the possible side effects, and the expected length of treatment.

Talking with your cancer care team before treatment begins about what to expect will be helpful. You’ll want to learn what you need to do before treatment begins, how you’ll feel while going through it, and what kind of help you will need. To learn more, visit Questions to Ask Your Doctor about Your Treatment.

Learn more at Stomach Cancer Treatment by Stage. 

Endoscopic mucosal resection

Endoscopic mucosal resection is a procedure that uses an endoscope to remove carcinoma in situ and early-stage cancer from the lining of the digestive tract. An endoscope is a thin, tube-like instrument with a light and a lens and tools to remove tissue.

Surgery

Surgery is a common treatment for stomach cancer. The type of surgery depends on where the cancer is located.

Other treatments may be given in addition to surgery:

  • Treatment given before surgery is called preoperative therapy or neoadjuvant therapy. Chemotherapy may be given before surgery to shrink the tumor and reduce the amount of tissue that needs to be removed during surgery. Chemoradiation given before surgery, to shrink the tumor, is being studied. 
  • Treatment given after surgery, to lower the risk that the cancer will come back, is called adjuvant therapy. After the doctor removes all the cancer that can be seen, some patients may be given chemotherapy, radiation therapy, or both to kill any cancer cells that are left.
Group of surgeons in caps and masks.
Cancer Surgery

Surgery, when used to treat cancer, is a procedure in which a surgeon removes cancer from your body. Learn the different ways that surgery is used against cancer and what you can expect before, during, and after surgery.

Gastrectomy

Gastrectomy, the removal of part or all of the stomach, is the main surgery for stomach cancer:  

  • Subtotal gastrectomy is the removal of the part of the stomach that contains cancer, nearby lymph nodes, and parts of other tissues and organs near the tumor. The spleen may also be removed.
  • Total gastrectomy is the removal of the entire stomach, nearby lymph nodes, and parts of the esophagus, small intestine, and other tissues near the tumor. The spleen may also be removed. Then the surgeon attaches the esophagus to the small intestine so the patient can continue to eat and swallow.

Endoluminal stent placement

Endoluminal stent placement may be done when the tumor blocks the passage into or out of the stomach. In this procedure, the surgeon places a stent (a thin, expandable tube) from the esophagus to the stomach or from the stomach to the small intestine to allow the patient to eat normally.

Endoluminal laser therapy

Endoluminal laser therapy is a procedure in which an endoscope (a thin, lighted tube) with a laser attached is used as a knife to open a gastrointestinal blockage.

Gastrojejunostomy

Gastrojejunostomy is the removal of the part of the stomach with cancer that is blocking the opening into the small intestine. Then the surgeon connects the stomach to the jejunum (a part of the small intestine) to allow food and medicine to pass from the stomach into the small intestine.

Radiation therapy

Radiation therapy uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. Stomach cancer is sometimes treated with external radiation therapy. This type of radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer.

Learn more about External Beam Radiation Therapy for Cancer and Radiation Therapy Side Effects.

Chemotherapy

Chemotherapy (also called chemo) uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 

Chemotherapy for stomach cancer is usually systemic, meaning it is injected into a vein or given by mouth. When given this way, the drugs enter the bloodstream to reach cancer cells throughout the body.  

Chemotherapy drugs used to treat stomach cancer include: 

To learn more about how chemotherapy works, how it is given, common side effects, and more, visit Chemotherapy to Treat Cancer and Chemotherapy and You: Support for People With Cancer.

Targeted therapy

Targeted therapy uses drugs or other substances to identify and attack specific cancer cells. Your doctor may suggest biomarker tests to help predict your response to certain targeted therapy drugs. Learn more about Biomarker Testing for Cancer Treatment.

Targeted therapies used to treat stomach cancer include:  

Learn more about Targeted Therapy to Treat Cancer.

Immunotherapy

Immunotherapy helps a person’s immune system fight cancer. Your doctor may suggest biomarker tests to help predict your response to certain immunotherapy drugs. Learn more about Biomarker Testing for Cancer Treatment. 

Immunotherapy drugs used to treat stomach cancer include:

These drugs work in more than one way to kill cancer cells. They are also considered targeted therapy because they target specific changes or substances in cancer cells.

Learn more about Immunotherapy to Treat Cancer and Immunotherapy Side Effects.

Hyperthermic intraperitoneal chemotherapy (HIPEC)

Regional chemotherapy is a method of placing chemotherapy directly into an organ or a body cavity, such as the abdomen, to mainly affect cancer cells in those areas.

A type of regional chemotherapy called hyperthermic intraperitoneal chemotherapy, or hot chemotherapy, is being studied to treat stomach cancer and may be offered at certain treatment centers. After the surgeon has removed as much of the cancer as possible during surgery, a chemotherapy drug, such as mitomycin or cisplatin, is warmed and pumped directly into the peritoneal cavity through a thin tube for about 2 hours. The surgeon then drains the chemotherapy from the abdomen and rinses the abdomen before closing the incision.

Clinical trials

A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. For some patients, taking part in a clinical trial may be an option.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. Clinical trials supported by other organizations can be found at ClinicalTrials.gov.

To learn more, visit Clinical Trials Information for Patients and Caregivers.

Contact Us for Help

Get live help finding a clinical trial at 1-800-4-CANCER. NCI offers free information on cancer topics in English and Spanish.

Follow-up testing

Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. These tests are sometimes called follow-up tests or check-ups.

You may also have blood tests for tumor markers such as CEA and CA 19-9. Increased levels of these markers may mean your stomach cancer has come back. Learn more about Tumor Markers.

Stomach Cancer Treatment by Stage

Photo of doctors talking to patients receiving intravenous (IV) medical treatment in an infusion room of a healthcare facility.

Chemotherapy works by killing fast-growing cancer cells and is one method used to treat stomach cancer.

 

Credit: iStock

Cancer stage is an important factor in deciding the best treatment for stomach cancer. Other factors, such as your preferences and overall health, are also important.  

For some people, taking part in a clinical trial may be an option. Clinical trials of new cancer drugs or treatment combinations may be available. To learn more about clinical trials, including how to find and join a trial, visit Clinical Trials Information for Patients and Caregivers.  

Treatment of stage 0 stomach cancer (carcinoma in situ)

Gastrectomy (surgery to remove all or part of the stomach and nearby lymph nodes) is the main treatment for stage 0 stomach cancer (carcinoma in situ). 

Endoscopic mucosal resection uses an endoscope to remove abnormal growths or tissue from the lining of the digestive tract without open surgery. It may be done in people with small tumors that have a low risk of spreading to nearby lymph nodes.

To learn more about these treatments, visit Stomach Cancer Treatment.  

Treatment of stage I stomach cancer

Gastrectomy (surgery to remove all or part of the stomach and nearby lymph nodes) is the main treatment for stage I stomach cancer. Some people may receive chemotherapy and/or radiation therapy before or after surgery. Giving chemotherapy at the same time as radiation therapy may help the radiation therapy work better.

There are many chemotherapy drugs used for stage I stomach cancer, including capecitabine, cisplatin, docetaxel, epirubicin, fluorouracil (5-FU), leucovorin, and oxaliplatin. These drugs may be given alone or in combination.

Endoscopic mucosal resection is a less invasive procedure that may be used in people with small tumors that have a low risk of spreading to nearby lymph nodes.

To learn more about these treatments, visit Stomach Cancer Treatment.

Treatment of stages II and III stomach cancer

Gastrectomy (surgery to remove all or part of the stomach and nearby lymph nodes) is the main treatment for stage II stomach cancer and stage III stomach cancer. Some people may receive chemotherapy and/or radiation therapy before or after surgery. Giving chemotherapy at the same time as radiation therapy may help the radiation therapy work better.

There are many chemotherapy drugs used for stage II and stage III stomach cancer, including capecitabine, cisplatin, docetaxel, epirubicin, fluorouracil (5-FU), leucovorin, and oxaliplatin. These drugs may be given alone or in combination.

To learn more about these treatments, visit Stomach Cancer Treatment.

Treatment of stage IV stomach cancer, stomach cancer that cannot be removed by surgery, and recurrent stomach cancer

Treatment of stage IV stomach cancer, any stage of stomach cancer that cannot be removed by surgery, and recurrent stomach cancer is palliative. Palliative therapy is treatment meant to improve the quality of life of people who have a serious or life-threatening disease, such as cancer. Many of the same treatments for cancer, such as chemotherapy or other kinds of drugs and radiation therapy, can also be used for palliative therapy to help a patient feel more comfortable. Learn more about Palliative Care in Cancer.  

The first palliative treatment for HER2-negative tumors might include chemotherapy with or without the immunotherapy drug nivolumab or chemotherapy with the targeted therapy drug zolbetuximab. For HER2-positive tumors, it might include the immunotherapy drug pembrolizumab and the targeted therapy drug trastuzumab combined with chemotherapy.  

Subsequent palliative therapy may include: 

There are many chemotherapy drugs used as palliative therapy for advanced stomach cancer, including capecitabine, cisplatin, docetaxel, doxorubicin, epirubicin, etoposide, fluorouracil (5-FU), irinotecan, leucovorin, oxaliplatin, paclitaxel, and trifluridine and tipiracil. These drugs may be given alone or in combination.   

A specific way of giving chemotherapy called hyperthermic intraperitoneal chemotherapy, or HIPEC, may be an option at some treatment centers. This treatment uses warmed chemotherapy to wash the inside of the abdomen during surgery.

If you have side effects from the cancer or its treatment, you may be given other treatments to help reduce those side effects so you are more comfortable. For example, if you have a blockage in your stomach, you may receive endoluminal laser therapy or endoluminal stent placement to relieve the blockage or a gastrojejunostomy to bypass the blockage. Radiation therapy or surgery may be done to stop bleeding, relieve pain, or shrink a tumor that is blocking the stomach.  

To learn more about these treatments, visit Stomach Cancer Treatment.

Stomach Cancer Diagnosis

If you have symptoms that suggest stomach cancer, your doctor will need to find out if they’re due to cancer or another condition. They may

  • ask about your personal and family medical history to learn about your possible risk factors for stomach cancer
  • do a physical exam, which will include feeling your abdomen for anything abnormal
  • run blood tests to check for anemia (a low red blood cell count), which could be a sign of bleeding in the stomach
  • check your stool for hidden (occult) blood, which could be a sign of bleeding in the stomach

Depending on these results, your doctor may recommend tests to find out if you have stomach cancer.

Tests to diagnose stomach cancer

The following tests and procedures are used to diagnose stomach cancer. The results will also help you and your doctor plan treatment.

Upper endoscopy with biopsy

Upper endoscopy is a procedure to look inside the esophagus, stomach, and duodenum (first part of the small intestine) to check for abnormal areas. An endoscope (a thin, lighted tube) is passed through the mouth and down the throat into the esophagus. It may also have a tool to remove a sample of cells or tissue (biopsy) so a pathologist can view it under a microscope to check for signs of cancer.

The sample of tissue may be checked for Helicobacter pylori (H. pylori) infection and used for biomarker testing.

Talk with your doctor to learn what to expect during and after your biopsy.

To learn about the type of information that can be found in a pathologist’s report about the cells or tissue removed during a biopsy, see Pathology Reports.

Upper endoscopy; drawing shows an endoscope (a thin, lighted tube) inserted through the mouth and down the throat into the esophagus and stomach. An inset shows a patient on a table having an upper endoscopy.

Upper endoscopy. A thin, lighted tube called an endoscope is inserted through the mouth and down the throat to check for abnormal areas in the esophagus, stomach, and first part of the small intestine.

Credit: © Terese Winslow

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Barium swallow

Barium swallow is a series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium (a silver-white metallic compound). The liquid coats the esophagus and stomach, and x-rays are taken. This procedure is also called an upper GI series.

Barium swallow; drawing shows barium liquid flowing down the esophagus and into the stomach. The barium coats and outlines the inside of the esophagus and stomach. Also shown is cancer in the stomach.

Barium swallow for stomach cancer. The patient drinks a liquid that contains barium (a silver-white metallic compound). The barium coats and outlines the inside of the esophagus and stomach. This allows abnormal areas, such as stomach cancer, to be seen on x-rays.

Credit: © Terese Winslow

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CT (CAT) scan

A CT scan uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body from different angles. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. To learn more, see Computed Tomography (CT) Scans and Cancer.

Biomarker testing

Biomarker testing is a way to look for genes, proteins, and other substances (called biomarkers or tumor markers) that can provide information about cancer. Some biomarkers affect how certain cancer treatments work. Biomarker testing may help you and your doctor choose a cancer treatment for you. 

To check for these biomarkers, samples of tissue containing stomach cancer cells are removed during a biopsy or surgery. The samples are tested in a laboratory to see whether the stomach cancer cells have these biomarkers.

For stomach cancer, biomarker testing includes the following:  

  • HER2: The cancer cells may have larger than normal amounts of a protein called HER2.  
  • PD-L1: The cells may have larger than normal amounts of an immune checkpoint protein called PD-L1.  
  • Microsatellite instability: The cells may have microsatellite instability. This may be caused by mistakes that don’t get corrected when DNA is copied in a cell. 
  • Mismatch repair deficiency: The cells may have a defect in a mismatch repair gene.  
  • Tumor mutational burden: If the cells have a high tumor mutational burden, it means they have many gene mutations. 
  • NTRK: The cells may have changes in one of the NTRK genes.

Learn more about Biomarker Testing for Cancer Treatment.  

Learn more about Stomach Cancer Treatment.

Tests to stage stomach cancer

Stomach Cancer Stages

Find information about a specific stage of stomach cancer, a factor that affects treatment.

If you’re diagnosed with stomach cancer, you will be referred to a gastrointestinal oncologist. This is a doctor who specializes in diagnosing and treating cancers of the stomach and intestines. Your doctor will recommend tests to find out if the cancer has spread and if so, how far. Sometimes the cancer is only in the stomach. Or, it may have spread from the stomach to other parts of the body. The process of learning the extent of cancer in the body is called staging. It is important to know the stage of the stomach cancer to plan treatment.

The following imaging tests and procedures may be used to find out your stage:

  • Endoscopic ultrasound is a procedure in which an endoscope is inserted into the body, usually through the mouth or rectum. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. A probe at the end of the endoscope is used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure is also called endosonography. 
  • PET-CT scan combines the pictures from a positron emission tomography (PET) scan and a computed tomography (CT) scan. The PET and CT scans are done at the same time on the same machine. The pictures from both scans are combined to make a more detailed picture than either test would make by itself. 
    • For the PET scan, a small amount of radioactive glucose is injected into a vein. The scanner rotates around the body and makes a picture of where glucose is being used in the body. Cancer cells show up brighter in the picture because they are more active and take up more glucose than normal cells.  
    • For the CT scan, a series of detailed x-ray pictures of areas inside the body is taken from different angles. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. 
  • Magnetic resonance imaging (MRI) with gadolinium is a procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI). 
  • Laparoscopy is a surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples to be checked under a microscope for signs of cancer. A solution may be washed over the surface of the organs in the abdomen and then removed to collect cells. These cells are also looked at under a microscope to check for signs of cancer.

Getting a second opinion

You may want to get a second opinion to confirm your stomach cancer diagnosis and treatment plan. If you seek a second opinion, you will need to get important medical test results and reports from the first doctor to share with the second doctor. The second doctor will review the pathology report, slides, and scans before giving a recommendation. The doctor who gives the second opinion may agree with your first doctor, suggest changes or another approach, or provide more information about your cancer.

To learn more about choosing a doctor and getting a second opinion, see Finding Health Care Services. For questions you might want to ask at your appointments, see Questions to Ask Your Doctor about Cancer.

Contact Us for Help

Get live help with finding a doctor, hospital, or getting a second opinion at 1-800-4-CANCER. NCI offers free information on cancer topics in English and Spanish.

Stomach Cancer Symptoms

Photo of a woman sitting on a couch, leaning slightly forward, with arms folded over abdomen.

Stomach pain or discomfort can be a symptom of stomach cancer.

Credit: iStock

Early on, stomach cancer usually doesn’t have symptoms, making it hard to detect. Symptoms usually begin after the cancer has spread.   

When symptoms of early-stage stomach cancer do occur, they may include  

  • indigestion and stomach discomfort
  • a bloated feeling after eating
  • mild nausea
  • loss of appetite
  • heartburn

Symptoms of advanced stomach cancer (cancer has spread beyond the stomach to other parts of the body) may include the symptoms of early-stage stomach cancer and

  • blood in the stool  
  • vomiting  
  • weight loss for no known reason  
  • stomach pain  
  • jaundice (yellowing of eyes and skin)  
  • ascites (buildup of fluid in the abdomen)  
  • trouble swallowing  

These symptoms may be caused by many conditions other than stomach cancer. It’s important to check with your doctor if you have any of these symptoms. Your doctor will ask when your symptoms started and how often you’ve been having them. If it is stomach cancer, ignoring symptoms can delay treatment and make it less effective.  

To learn more, see Stomach Cancer Diagnosis.