Treatment statement for Health professionals

Ovarian Germ Cell Tumors Treatment (PDQ®)

Get this document via a secure connection

Purpose of This PDQ Summary
General Information
Cellular Classification
Stage Information
Treatment Option Overview
Stage I Ovarian Germ Cell Tumors
Stage II Ovarian Germ Cell Tumors
Stage III Ovarian Germ Cell Tumors
Stage IV Ovarian Germ Cell Tumors
Recurrent Ovarian Germ Cell Tumors
Get More Information From NCI
Changes to This Summary (05/22/2008)
More Information

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of ovarian germ cell tumors. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.

Information about the following is included in this summary:

Prognostic factors.
Cellular classification.
Staging.
Treatment options by cancer stage.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the 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. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

General Information

Germ cell tumors of the ovary, uncommon but aggressive tumors seen most often in young women or adolescent girls, are frequently unilateral, and are generally curable if found and treated early. Use of combination chemotherapy after initial surgery has dramatically improved the prognosis for many women with these tumors. [1] [2] [3] Although long-term survival is the rule for mature teratoma, survival for immature teratoma following surgery only is related to the grade of the tumor, especially its neural elements. In a series of 58 patients with immature teratoma treated before the modern chemotherapeutic era, Norris et al. reported recurrence in 18% with grade 1 disease, in 37% with grade 2 disease, and in 70% with grade 3 disease, and similar findings have been reported by others. [4] Endodermal sinus tumors of the ovary are particularly aggressive. A review of the literature in 1979 prior to the widespread use of combination chemotherapy, found only 27% of 96 patients with stage I endodermal sinus tumor alive at 2 years. Over 50% died within a year of diagnosis. [5]

Other studies found that size and histology were the major factors determining prognosis for patients with malignant mixed germ cell tumors of the ovary. [4] [6] Prognosis was poor for large tumors when more than one-third of the tumor was composed of endodermal sinus elements, choriocarcinoma or grade 3 immature teratoma. On the other hand, when the tumor was less than 10 cms in diameter, the prognosis was good regardless of the composition of the tumor. [6]

For dysgerminoma confined to the ovary, less than 10 centimeters in size, with an intact, smooth capsule unattached to other organs and without ascites, the 10-year survival following conservative surgery was 88.6% in a series, and a number of patients had 1 or more successful pregnancies following unilateral salpingo-oophorectomy. [7] Even patients with incompletely resected dysgerminoma can be rendered disease free following BEP (bleomycin/etoposide/cisplatin) or PVB (cisplatin/vinblastine/bleomycin) chemotherapy. [8] A report of 35 cases of germ cell tumors, half of which were advanced stage or recurrent or progressive disease, demonstrated a 97% sustained remission at 10 to 54 months after the start of BEP chemotherapy. [1] Also, reported results of 2 Gynecologic Oncology Group (GOG) trials show that 89 of 93 patients with stages I, II, and III disease who had completely resected tumors were disease free after 3 cycles of BEP. [1] [3] However, in a similar nonseminomatous germ cell tumor of the testis, the combination of bleomycin, etoposide, and carboplatin (CEB) was inferior to BEP in a randomized multicenter trial comparing BEP to CEB in 598 patients with good-risk nonseminomatous testicular germ cell tumors. [9]

References:

Cellular Classification

The following histologic subtypes have been described. [1] [2]

Dysgerminoma.
Other germ cell tumors.
- Endodermal sinus tumor (rare subtypes are hepatoid and intestinal). [1]
- Embryonal carcinoma.
- Olyembryoma.
- Choriocarcinoma.
- Teratoma:
  - Immature.
  - Mature:
    - Solid.
    - Cystic:
      - Dermoid cyst (mature cystic teratoma).
      - Dermoid cyst with malignant transformation.
  - Monodermal and highly specialized:
    - Struma ovarii.
    - Carcinoid.
    - Struma ovarii and carcinoid.
    - Others (e.g., malignant neuroectodermal and ependymoma).
- Mixed forms.

References:

Stage Information

In the absence of obvious metastatic disease, accurate staging of germ cell tumors of the ovary requires laparotomy with careful examination of the entire diaphragm, both paracolic gutters, pelvic nodes on the side of the ovarian tumor, the para-aortic lymph nodes, and the omentum. The contralateral ovary should be carefully examined and biopsied if necessary. Ascitic fluid should be examined cytologically. If ascites is not present, it is important to obtain peritoneal washings before the tumor is manipulated. In patients with dysgerminoma, lymphangiography or computed tomography is indicated if the pelvic and para-aortic lymph nodes were not carefully examined at surgery. Although not required for formal staging, it is desirable to obtain serum levels of alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG) as soon as the diagnosis is established since persistence of these markers in the serum after surgery indicates unresected tumor.

The Federation Internationale de Gynecologie et d’Obstetrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging. [1] [2]

Stage I

Stage I ovarian germ cell cancer is growth limited to the ovaries.

Stage IA: Tumor is limited to 1 ovary; capsule is intact, and no tumor is present on the ovarian surface. No malignant cells are present in ascites or peritoneal washings.*
Stage IB: Tumor is limited to both ovaries; capsules are intact, no tumor is present on the ovarian surface. No malignant cells are present in ascites or peritoneal washings.*
Stage IC: Tumor is limited to 1 or both ovaries with any of the following: capsule is ruptured, tumor is present on the ovarian surface, malignant cells are present in ascites or peritoneal washings. [1]

*Malignant ascites is not classified. The presence of ascites does not affect staging unless malignant cells are present.

Stage II

Stage II ovarian germ cell cancer is growth involving 1 or both ovaries with pelvic extension and/or implants.

Stage IIA: Extension and/or implants are present on the uterus and/or fallopian tubes. No malignant cells are present in ascites or peritoneal washings.
Stage IIB: Extension to and/or implants are present on other pelvic tissues. No malignant cells are present in ascites or peritoneal washings.
Stage IIC: Pelvic extension and/or implants (stage IIA or stage IIB) with malignant cells are present in ascites or peritoneal washings.

Different criteria for designating cases to stages IC and IIC have an impact on the diagnoses. To evaluate the impact, determine if rupture of the capsule was (1) spontaneous or (2) caused by the surgeon, and if the source of the malignant cells detected was (1) peritoneal washings or (2) ascites.

Stage III

Stage III ovarian germ cell cancer is growth involving 1 or both ovaries with microscopically confirmed peritoneal implants outside the pelvis. Superficial liver metastasis equals stage III. Tumor is limited to the true pelvis but with histologically verified malignant extension to the small bowel or omentum.

Stage IIIA: Microscopic peritoneal metastasis is present beyond the pelvis (no macroscopic tumor).
Stage IIIB: Macroscopic peritoneal metastasis is present beyond the pelvis and ≤2 cm in greatest dimension.
Stage IIIC: Peritoneal metastasis is present beyond the pelvis and is >2 cm in greatest dimension, and/or regional lymph node metastasis is present.

Stage IV

Stage IV ovarian germ cell cancer is growth involving 1 or both ovaries with distant metastasis. If pleural effusion is present, there must be positive cytologic test results to designate a case to stage IV. Parenchymal liver metastasis equals stage IV.

References:

Treatment Option Overview

All patients except those with stage I, grade I immature teratoma and stage IA dysgerminoma require postoperative chemotherapy. With platinum-based combination chemotherapy, the prognosis for patients with endodermal sinus tumors, immature teratomas, embryonal carcinomas, choriocarcinomas, and mixed tumors containing 1 or more of these elements has improved dramatically. [1] As new and more effective drugs are developed, many of these patients will be candidates for newer clinical trials.

References:

Gershenson DM, Morris M, Cangir A, et al.: Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin. J Clin Oncol 8 (4): 715-20, 1990.

Stage I Ovarian Germ Cell Tumors

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Dysgerminomas

Standard treatment options:

For patients with stage I dysgerminoma, unilateral salpingo-oophorectomy conserving the uterus and opposite ovary is accepted treatment of the younger patient anxious to preserve fertility or to preserve a pregnancy. Postoperative lymphangiography or computed tomography is indicated before treatment decisions are made for patients who have not had careful surgical and pathological examination of pelvic and para-aortic lymph nodes during surgery.
Patients who have been completely staged and have stage IA tumors may be observed carefully after surgery without adjuvant treatment. About 15% to 25% will recur, but can be treated successfully at the time of recurrence with a high likelihood of cure. Incompletely staged patients or those with higher stage tumors probably should receive adjuvant treatment. Options include radiation therapy or chemotherapy. A disadvantage of the former is loss of fertility due to ovarian failure. Experience with adjuvant chemotherapy is limited, but considering the effectiveness of chemotherapy in tumors other than dysgerminoma and in advanced stage dysgerminoma, it is likely to be very effective and to allow recovery of reproductive potential in patients with an intact ovary, tube, and uterus. [1]

Other Germ Cell Tumors

Standard treatment options:

For patients with stage I germ cell tumors, unilateral salpingo-oophorectomy should be performed when fertility is to be preserved. For all tumors other than pure dysgerminoma and low-grade (grade I) immature teratoma, chemotherapy is usually given postoperatively, although a series demonstrated excellent survival for all types of stage I tumors managed by surveillance, reserving chemotherapy for cases in which post-surgery recurrence is documented. [2][Level of evidence: 3iiiA] There is considerable experience with VAC, a combination of vincristine, dactinomycin, and cyclophosphamide given in an adjuvant setting, however, combinations containing cisplatin, etoposide, and bleomycin (BEP) are now preferred because of a lower relapse rate and shorter treatment time. [3] While a prospective comparison of VAC versus BEP has not been performed, it should be noted that in well-staged patients with completely resected tumors, relapse is essentially unheard of following platinum-based chemotherapy. [3] However, the disease will recur in about 25% of well-staged patients treated with 6 months of VAC. [4]
Evidence suggests that second-look laparotomy is not beneficial in patients with initially completely resected tumors who receive cisplatin-based adjuvant treatment. [5] [6]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I ovarian germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Stage II Ovarian Germ Cell Tumors

Dysgerminomas

Standard treatment options:

For patients with stage II dysgerminoma, total abdominal hysterectomy and bilateral salpingo-oophorectomy are usually performed. However, for the younger patient anxious to preserve fertility, a unilateral salpingo-oophorectomy can be considered standard therapy at this time; adjuvant chemotherapy should be given.
These patients should receive adjuvant treatment. Options include radiation therapy or chemotherapy. A disadvantage of the former is loss of fertility due to ovarian failure. Experience with adjuvant chemotherapy is limited, but considering the effectiveness of chemotherapy in tumors other than dysgerminoma and in advanced stage dysgerminoma, it is likely to be effective and to allow recovery of reproductive potential in patients with an intact ovary, tube, and uterus. Thus, adjuvant cisplatin, etoposide, and bleomycin have replaced radiation therapy except in the rare patient in whom chemotherapy is not considered appropriate.

Other Germ Cell Tumors

Standard treatment options:

For patients with stage II germ cell tumors other than pure dysgerminoma, unilateral salpingo-oophorectomy should be performed when fertility is to be preserved. Although there is considerable experience with VAC (vincristine/dactinomycin/cyclophosphamide), especially when given in an adjuvant setting, combinations containing bleomycin, etoposide, and cisplatin (BEP) are more effective. [1] [2] [3] Patients who do not respond to a cisplatin-based combination may still attain a durable remission with VAC as salvage therapy. [4] Recurrence after 3 courses of BEP as adjuvant therapy is rare. [4] All patients who do not respond to standard therapy are candidates for clinical trials. When there is residual disease or elevated levels of AFP or HCG after maximal surgical debulking, 3 or 4 courses of BEP combination chemotherapy are indicated. [5]
Evidence suggests that second-look laparotomy is not beneficial in patients with initially completely resected tumors who receive cisplatin-based adjuvant treatment. [6] Second-look surgery may be of benefit for a minority of patients whose tumor was not completely resected at the initial surgical procedure and who had teratomatous elements in their primary tumor. [6] [7] Surgical resection of residual masses detected by clinical examination, by radiographic procedures, or at re-exploration should be undertaken since reversion to germ cell tumor has been described.

Treatment options under clinical evaluation:

Patients with stage II germ cell tumors of the ovary are candidates for clinical trials. [4]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II ovarian germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Stage III Ovarian Germ Cell Tumors

Dysgerminomas

Standard treatment options:

For patients with stage III dysgerminoma, total abdominal hysterectomy and bilateral salpingo-oophorectomy are recommended with removal of as much gross tumor as can be done safely without resection of portions of the urinary tract or large segments of small or large bowel. Patients who wish to preserve fertility may be treated with unilateral salpingo-oophorectomy if chemotherapy is to be employed. [1] [2] [3] [4] [5]
Chemotherapy with bleomycin/etoposide/cisplatin (BEP) can cure the majority of such patients. In a report of results from 2 Gynecologic Oncology Group (GOG) trials, 19 of 20 patients with incompletely resected tumor who were treated with BEP or PVB were diseasefree at a median follow-up of 26 months. [1] When there is bulky residual disease, it is common to give 3 to 4 courses of a cisplatin-containing combination such as PVB or BEP. [6] [7] [8] A randomized study in testicular cancer has shown that bleomycin is an essential component of the BEP regime when only 3 courses are administered. [9] Since chemotherapy with BEP appears to be less sterilizing than wide-field radiation, combination chemotherapy is the preferred treatment in the patient who still desires to have children. [1]

Other Germ Cell Tumors

Standard treatment options:

For patients with stage III germ cell tumors other than pure dysgerminoma, total abdominal hysterectomy and bilateral salpingo-oophorectomy is recommended with removal of as much tumor in the abdomen and pelvis as can be done safely without resection of portions of the urinary tract or large segments of small or large bowel. Patients who wish to preserve fertility can be treated with unilateral salpingo-oophorectomy. [1] [3] [4] For patients with extensive intra-abdominal disease whose clinical condition precludes debulking surgery, chemotherapy can be considered prior to surgery. Following maximal surgical debulking, 3 to 4 courses of cisplatin-containing combination chemotherapy are indicated. [2] [6] [10]
Evidence suggests that second-look laparotomy is not beneficial in patients with initially completely resected tumors who receive cisplatin-based adjuvant treatment. [11] Patients who do not respond to a cisplatin/etoposide-based combination may still attain a durable remission with VAC or cisplatin/vinblastine/ifosfamide as salvage therapy. [6] Second-look surgery may be of benefit for a minority of patients whose tumor was not completely resected at the initial surgical procedure and who had teratomatous elements in their primary tumor. [11] Surgical resection of residual masses detected by clinical examination, by radiographic procedures, or at re-exploration should be undertaken since reversion to germ cell tumor or progressive teratoma has been described.

Treatment options under clinical evaluation:

Patients with stage III germ cell tumors of the ovary, including pure dysgerminoma, are candidates for clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III ovarian germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Stage IV Ovarian Germ Cell Tumors

Dysgerminomas

Standard treatment options:

For patients with stage IV dysgerminoma, total abdominal hysterectomy and bilateral salpingo-oophorectomy is recommended with removal of as much gross tumor in the abdomen and pelvis as can be done safely without resection of portions of the urinary tract or large segments of small or large bowel, although unilateral salpingo-oophorectomy should be considered in patients who wish to preserve fertility. [1] [2] Chemotherapy with bleomycin/etoposide/cisplatin (BEP) can cure the majority of such patients. Stage IV dysgerminoma is not treated with radiation therapy, but rather with chemotherapy, preferably with 3 to 4 courses of cisplatin-containing combination chemotherapy such as BEP. [1] A second-look operation following treatment is rarely beneficial.

Other Germ Cell Tumors

Standard treatment options:

For patients with stage IV germ cell tumors other than pure dysgerminoma, total abdominal hysterectomy and bilateral salpingo-oophorectomy is recommended with removal of as much tumor from the abdomen and pelvis as can be done safely without resection of kidney or large segments of small or large bowel. Patients who wish to preserve fertility can be treated with unilateral salpingo-oophorectomy. Following maximal surgical debulking, three to four courses of cisplatin-containing combination chemotherapy are indicated. [3] [4] For patients with extensive intra-abdominal disease whose clinical condition precludes debulking surgery, chemotherapy can be considered prior to surgery. Patients who do not respond to a cisplatin/etoposide-based combination may still attain a durable remission with VAC or cisplatin/vinblastine/ifosfamide as salvage therapy. [4] Second-look surgery may be of benefit for a minority of patients whose tumor was not completely resected at the initial surgical procedure and who had teratomatous elements in their primary tumor. [5] [6] Surgical resection of residual masses detected by clinical examination, by radiographic procedures, or at re-exploration should be undertaken since reversion to germ cell tumor or progressive teratoma has been described.

Treatment options under clinical evaluation:

Patients with stage IV germ cell tumors of the ovary (including pure dysgerminoma) are candidates for clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV ovarian germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Recurrent Ovarian Germ Cell Tumors

Dysgerminomas

Standard treatment options:

Cisplatin-based chemotherapy has been used effectively for patients with recurrent dysgerminoma with and without adjuvant radiation therapy. [1]

Other Germ Cell Tumors

Standard treatment options:

Patients with recurrent germ cell tumors of the ovary other than pure dysgerminoma should be treated with chemotherapy, the type of which is determined by previous treatment. [2] Radiation therapy is not effective in this setting. Cisplatin-based combination chemotherapy is effective. [1] [3] [4] Patients who do not respond to a cisplatin-based combination may still attain a durable remission with VAC or ifosfamide/cisplatin as salvage therapy. [1] Newer potential treatments include an ifosfamide combination [5] or high-dose chemotherapy and autologous marrow rescue. [6] [7] [8] Although the role of secondary cytoreductive surgery for patients with recurrent or progressive ovarian germ cell tumors remains controversial, it may have some benefit for a select group of patients, particularly those with immature teratoma. [9] After maximal effort for surgical cytoreduction, chemotherapy should be considered.

Treatment options under clinical evaluation:

Patients with recurrent germ cell tumors of the ovary (including pure dysgerminoma) are candidates for clinical trials. Some consideration should be given to the use of high-dose regimens with rescue (GOG-90).

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent ovarian germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Get More Information From NCI

Call 1-800-4-CANCER

For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. A trained Cancer Information Specialist is available to answer your questions.

Chat online

The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

Write to us

For more information from the NCI, please write to this address:

NCI Public Inquiries Office
Suite 3036A
6116 Executive Boulevard, MSC8322
Bethesda, MD 20892-8322

Search the NCI Web site

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

Find Publications

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).

Changes to This Summary (05/22/2008)

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.

Editorial changes were made to this summary.

More Information

About PDQ

PDQ® - NCI's Comprehensive Cancer Database.
- Full description of the NCI PDQ database.

Additional PDQ Summaries

PDQ® Cancer Information Summaries: Adult Treatment
- Treatment options for adult cancers.
PDQ® Cancer Information Summaries: Pediatric Treatment
- Treatment options for childhood cancers.
PDQ® Cancer Information Summaries: Supportive and Palliative Care
- Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
- Tests or procedures that detect specific types of cancer.
PDQ® Cancer Information Summaries: Prevention
- Risk factors and methods to increase chances of preventing specific types of cancer.
PDQ® Cancer Information Summaries: Genetics
- Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
- Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Date last modified: 2008-05-22

Sponsors:
The following organisations have financed parts of our PhD research project on improving the quality of online cancer information.

The Commission of the European Communities, Directorate General XIII by contract INCO 962100 (ARGONAUTA)
Health on the Net Foundation (Geneva)
Landesregierung NRW (im Rahmen von HSP III)

Back to the Cancer.gov contents overview
Questions? Mail them to us!

We subscribe to the HONcode principles
of the Health On the Net Foundation

Dr. G. Quade

This page was last modified on Tuesday, 02-Feb-2010 12:49:25 CET

Impressum