General Information About Ovarian Germ Cell Tumors

Germ cell tumors of the ovary are uncommon, but aggressive, tumors, which are seen most often in young women or adolescent girls. These tumors are frequently unilateral and are generally curable if found and treated early. The use of combination chemotherapy after initial surgery has dramatically improved the prognosis for many women with these tumors.[1,2,3]

Dysgerminomas

One series found a 10-year survival rate of 88.6% following conservative surgery for patients with dysgerminoma confined to the ovary; less than 10 cm in size; with an intact, smooth capsule unattached to other organs; and without ascites.[4] A number of patients had one or more successful pregnancies following unilateral salpingo-oophorectomy.[4] Even patients with incompletely resected dysgerminoma can be rendered disease-free following chemotherapy with bleomycin, etoposide, and cisplatin (BEP) or a combination of cisplatin, vinblastine, and bleomycin, also known as PVB.[5]

Other Germ Cell Tumors

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 months to 54 months after the start of a combination of BEP.[1] Two Gynecologic Oncology Group trials reported that 89 of 93 patients with stage I, II, or III disease who had completely resected tumors were disease-free after three cycles of BEP.[1,3]

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 after diagnosis. More than 50% of the patients died within a year of diagnosis.

Patients with mature teratomas usually experience long-term survival, but survival for patients with immature teratomas 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, recurrence was reported in 18% of the patients with grade 1 disease, in 37% of the patients with grade 2 disease, and in 70% of the patients with grade 3 disease.[6] Similar findings have been reported by others.[7]

Some studies have found that size and histology were the major factors determining prognosis for patients with malignant mixed germ cell tumors of the ovary.[6,8] Prognosis was poor for patients with large tumors when more than one-third of the tumor was composed of endodermal sinus elements, choriocarcinoma, or grade 3 immature teratoma. When the tumor was smaller than 10 cm in diameter, the prognosis was good regardless of the composition of the tumor.[8,9]

References:

Cellular Classification of Ovarian Germ Cell Tumors

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 for Ovarian Germ Cell Tumors

Note: The American Joint Committee on Cancer has recently published a new edition of the AJCC Cancer Staging Manual, which includes revisions to the staging for this disease. The PDQ Adult Treatment Editorial Board, which is responsible for maintaining this summary, is currently reviewing the new staging to determine the changes that need to be made in the summary. In addition to updating this Stage Information section, additional changes may need to be made to other parts of this summary to ensure that it is up-to-date. The changes will be made as soon as possible.

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 the time of 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 for ovarian germ cell tumors.[1,2]

Stage I

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

• Stage IA: Tumor is limited to 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 one or both ovaries with any of the following:[1]
  • Capsule is ruptured.
  • Tumor is present on the ovarian surface.
  • Malignant cells are present in ascites or peritoneal washings.

*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 one 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 of the differing criteria, determine if rupture of the capsule was the result of any of the following possibilities:

• A spontaneous rupture.
• A rupture caused by the surgeon.

It is also important to determine if the source of the malignant cells detected was the result of either of the following:

• Peritoneal washings.
• Ascites.

Stage III

Stage III ovarian germ cell cancer is growth involving one 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 is 2 cm or smaller in greatest dimension.
• Stage IIIC: Peritoneal metastasis is present beyond the pelvis and is larger than 2 cm in greatest dimension, and/or regional lymph node metastasis is present.

Stage IV

Stage IV ovarian germ cell cancer is growth involving one 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

Standard treatment options for patients with ovarian germ cell tumors include:

• Surgery.
• Chemotherapy.
• Radiation therapy.

Patients may be treated with unilateral salpingo-oophorectomy or total abdominal hysterectomy and bilateral salpingo-oophorectomy.

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 one 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.

Treatment options under clinical evaluation for patients with ovarian germ cell tumors include:

• High-dose chemotherapy with bone marrow transplant.
• New treatment options.

References:

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 who wants to preserve fertility or a pregnancy. Postoperative lymphangiography or CT 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. (For more information on fertility, refer to the Sexuality and Reproductive Issues summary.)

Patients who have been completely staged and have stage IA tumors may be observed carefully after surgery without adjuvant treatment. About 15% to 25% of these patients will relapse, but they can be treated successfully at the time of recurrence with a high likelihood of cure.

Incompletely staged patients or those with higher stage tumors should probably receive adjuvant treatment. Options include radiation therapy or chemotherapy. A disadvantage of the former is loss of fertility resulting from ovarian failure. Experience with adjuvant chemotherapy is limited, but considering the effectiveness of chemotherapy in tumors other than dysgerminoma and in advanced stage dysgerminoma, adjuvant chemotherapy is likely to be very effective and to allow recovery of reproductive potential in patients with an intact ovary, fallopian 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 patients with tumors other than pure dysgerminoma and low-grade (grade I) immature teratoma, chemotherapy is usually given postoperatively, although a series demonstrated excellent survival for patients with all types of stage I tumors managed by surveillance, reserving chemotherapy for cases in which postsurgery recurrence is documented.[2][Level of evidence: 3iiiA]

There is considerable experience with a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) 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, 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 list of cancer clinical trials 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. For the younger patient who wants to preserve fertility, a unilateral salpingo-oophorectomy may be considered standard therapy, depending on the age of the patient, and adjuvant chemotherapy should be given. (For more information on fertility, refer to the Sexuality and Reproductive Issues summary.

These patients should receive adjuvant treatment. Options include radiation therapy or chemotherapy. A disadvantage of the former is loss of fertility resulting from ovarian failure. Experience with adjuvant chemotherapy is limited, but considering the effectiveness of chemotherapy in tumors other than dysgerminoma and its effectiveness in advanced-stage dysgerminoma, adjuvant chemotherapy is likely to be effective and to allow recovery of reproductive potential in patients with an intact ovary, fallopian tube, and uterus. Thus, adjuvant chemotherapy with the combination of bleomycin, etoposide, and cisplatin (BEP) has replaced radiation therapy except in the rare patient in whom chemotherapy is not considered appropriate.

Treatment options under clinical evaluation:

• Patients with stage II germ cell tumors of the ovary are candidates for clinical trials.[1]

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 the combination of vincristine, dactinomycin, and cyclophosphamide (VAC), especially when given in an adjuvant setting, BEP is more effective.[2,3,4] Patients who do not respond to a cisplatin-based combination may still attain a durable remission with VAC as salvage therapy.[1] Recurrence after three courses of BEP as adjuvant therapy is rare.[1] All patients who do not respond to standard therapy are candidates for clinical trials. When there is residual disease or elevated levels of alpha-fetoprotein or human chorionic gonadotropin after maximal surgical debulking, three or four 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.[1]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials 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 the small or large bowel. Patients who want to preserve fertility may be treated with unilateral salpingo-oophorectomy if chemotherapy is to be employed.[1,2,3,4,5] (For more information on fertility, refer to the Sexuality and Reproductive Issues summary.)

Combination chemotherapy with bleomycin, etoposide, and cisplatin (BEP) can cure the majority of such patients. In a report of results from two Gynecologic Oncology Group (GOG) trials, 19 of 20 patients with incompletely resected tumors who were treated with BEP or cisplatin, vinblastine, and bleomycin (PVB) were disease-free at a median follow-up of 26 months.[1] When there is bulky residual disease, it is common to give three to four 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 three courses are administered.[9] Because chemotherapy with BEP appears to be less sterilizing than wide-field radiation, combination chemotherapy is the preferred treatment in the patient who wants to preserve fertility.[1]

Treatment options under clinical evaluation:

• Patients with stage III germ cell tumors of the ovary are candidates for clinical trials.

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 the 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, three to four courses of cisplatin-containing combination chemotherapy are indicated.[2,6,10] (For more information on fertility, refer to the Sexuality and Reproductive Issues summary.)

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 a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) or a combination of cisplatin, vinblastine, and 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 are candidates for clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials 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 three to four courses of cisplatin-containing combination chemotherapy such as BEP.[1] A second-look operation following treatment is rarely beneficial. (For more information on fertility, refer to the Sexuality and Reproductive Issues summary.)

Treatment options under clinical evaluation:

• Patients with stage IV germ cell tumors of the ovary are candidates for clinical trials.

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 the kidney or large segments of the 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] (For more information on fertility, refer to the Sexuality and Reproductive Issues summary.)

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 are candidates for clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials 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]

Treatment options under clinical evaluation:

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

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 are candidates for clinical trials. Some consideration should be given to the use of high-dose regimens with rescue.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials 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:

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Changes to This Summary (03 / 05 / 2010)

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

General Information About Ovarian Germ Cell Tumors

Added Murugaesu et al. as reference 9.

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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 ovarian germ cell tumors. It 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.

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The lead reviewer for Ovarian Germ Cell Tumors Treatment is:

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Last Revised: 2010-03-05