Ovarian Germ Cell Tumor Treatment Protocols

Surgical staging is the first step in the management of ovarian germ cell cancer.[1] Staging includes peritoneal cytology, hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and exploration of peritoneal surfaces and diaphragm with biopsies.

If disease appears to be limited to the ovaries or pelvis, a pelvic and para-aortic lymphadenectomy should also be performed. If disease involves the upper abdomen, a surgical effort to remove all visible tumor should be made. However, in view of the excellent chemosensitivity of germ cell cancers, clinical judgment can be used if surgical management would significantly increase postoperative morbidity.[2]

Such judgment is important, especially in younger patients who desire future fertility. In these cases, fertility-sparing surgery must be considered. This includes the same comprehensive surgical staging but allows preservation of the uterus and the unaffected contralateral ovary.[3]

Tumor markers, including Ca-125, alpha-fetoprotein, lactate dehydrogenase (LDH), and beta–human chorionic gonadotropin (beta-hCG) may be evaluated before surgery. Pregnancy must be excluded if beta-hCG levels are elevated.

Treatment recommendations for stage IA dysgerminomas and IA grade 1 immature teratomas

Observation is recommended after surgical staging. Upon recurrence, chemotherapy is instituted as outlined below.

Treatment recommendations for all other malignant germ cell tumors

In patients with embryonal or endodermal sinus tumors, stage II-IV dysgerminoma, or stage 1 (grade 2-3) or stage II-IV immature teratoma, standard postoperative adjuvant chemotherapy for three or four cycles with bleomycin-etoposide-cisplatin (BEP) is recommended, as follows[4] :

• Bleomycin 30 units/wk IV on days 1, 8, and 15 plus
• Etoposide 100 mg/m ²/day IV and
• Cisplatin 20 mg/m ²/day IV on days 1-5
• BEP is given every 21 d for three cycles (or four cycles if the patient had bulky residual disease after surgery)
• Pulmonary function tests are recommended if bleomycin is considered

For completely resected stage IB-III dysgerminoma, an alternative regimen for minimizing toxicity in selected cases consists of etoposide-carboplatin (EP), as follows[5] :

• Carboplatin 400 mg/m ² IV on day 1 plus
• Etoposide 120 mg/m ² IV on days 1-3
• EP is given every 28 d for three cycles

In the rare case of somatic tumors arising within a benign teratoma, the choice of systemic therapy should be guided by the specific disease type. For example, squamous carcinoma, thyroid carcinoma, melanoma, or carcinoid should be treated as such.[3]

Treatment recommendations for recurrent or residual disease after initial chemotherapy

If residual disease is apparent on imaging but tumor markers are not elevated, surgical excision should be considered for diagnosis; residual lesions may represent benign mature teratoma rather than malignancy.[6]

In the event of recurrence, confirmed residual disease, or elevated tumor markers after first-line chemotherapy, recommended treatment consists of paclitaxel (Taxol)-ifosfamide-cisplatin (TIP) or high-dose chemotherapy.[7] TIP is given as follows:

• Paclitaxel 250 mg/m ² IV infused over 24 h on day 1 plus
• Ifosfamide 1500 mg/m ²/day IV and
• Cisplatin 25 mg/m ²/day IV on days 2-6
• TIP is given every 21 d for four cycles

Other acceptable regimens include the following:

• Cisplatin-etoposide
• Docetaxel
• Docetaxel-carboplatin
• Paclitaxel
• Paclitaxel-ifosfamide
• Paclitaxel-carboplatin
• Paclitaxel- gemcitabine
• Etoposide-ifosfamide-cisplatin
• Vinblastine-ifosfamide-cisplatin
• Vincristine- dactinomycin- cyclophosphamide
• Radiation therapy

Especially in cases of platinum-resistant disease (< 6 mo from end of treatment), National Comprehensive Cancer Network (NCCN) guidelines strongly recommend referral to a tertiary care center for consultation regarding high-dose chemotherapy, which is potentially curative in some patients.[7]

Special considerations

Bleomycin pulmonary toxicity must be considered when patients develop difficulty in breathing and have fine rales on examination. A pulmonary workup, including evaluation of diffusing capacity for carbon monoxide (DLCO), should be performed for assessment.