Staging: Ovarian carcinoma is a surgically staged disease. The current staging classification system is based on 1987 International Federation of Gynecology and Obstetrics (FIGO) nomenclature.
Stage I: Tumor is confined to the ovaries.
Stage Ia: Tumor is limited to one ovary with an intact capsule. No tumor is present on the external surface of the capsule, and no ascites containing malignant cells are present.
Stage Ib: Tumor involves both ovaries, with intact capsules. No tumor is present on the external surface of the capsule, and no ascites containing malignant cells are present.
Stage Ic: Tumor is stage Ia or Ib with tumor on the external surface of one or both ovaries, or ruptured capsule(s) or malignant cells are present in ascitic fluid or peritoneal washings.
Stage II: Tumor involves one or both ovaries, with pelvic extension.
Stage IIa: Extension and/or metastases to the uterus and/or fallopian tubes are present.
Stage IIb: Extension to the bladder, rectum, or other pelvic tissues occurs.
Stage IIc: Tumor is stage IIa or IIb, with tumor on the external surface of one or both ovaries or ruptured capsule(s), or malignant cells are present in ascitic fluid or peritoneal washings.
Stage III: Tumor involves one or both ovaries, with peritoneal implants outside of the pelvis and/or positive retroperitoneal lymph nodes. Superficial liver metastases also are included in stage III.
Stage IIIa: Tumor is grossly confined to the pelvis but with microscopic seeding of the abdominal peritoneal surfaces. Lymph nodes are negative.
Stage IIIb: Tumor implants are present on the abdominal peritoneum, none larger than 2 cm in diameter. Lymph nodes are negative.
Stage IIIc: Tumor implants on the abdominal peritoneum 2 cm or more are present, and/or retroperitoneal or inguinal nodes are positive.
Stage IV: Distant metastases are present.
Pleural effusions must be confirmed cytologically to classify a case as stage IV.
Metastases to the liver parenchyma also are included in stage IV.
Medical Care:
Primary treatment for patients with GCTs always is surgical. Chemotherapy and/or radiotherapy are reserved for patients with advanced disease, as confirmed by surgical staging, and for patients with recurrent tumor.
Treatment for patients postoperatively consists of frequent pelvic examinations and assessment of tumor markers (if applicable) in order to detect recurrences at an early stage. Findings from physical examination or laboratory studies that are suggestive of recurrence should be further evaluated with abdominopelvic CT scan or other diagnostic imaging modalities.
Radiotherapy for patients with advanced or recurrent GCTs has been studied and appears to have limited efficacy. In a 1999 study by Wolf et al, of 14 patients with measurable disease at the MD Anderson Cancer Center, 6 patients had complete clinical responses but 3 experienced recurrence. Eight of 14 had no response to treatment and had a median survival of 12.3 months overall. In patients with pelvic recurrences, radiotherapy should be considered because a clinical response occurs in almost half the patients treated with radiation therapy.
Treatment of recurrent GCTs with leuprolide acetate has been described but exhibited only marginal success in a small number of patients.
Surgical Care:
Surgical care of patients suggested to have GCTs begins with a thorough preoperative evaluation and preparation.
Preoperative imaging and laboratory studies are helpful for measuring the extent of disease so that patients may be counseled appropriately (see Lab Studies and Imaging Studies).
Appropriate staging with intact removal of the tumor and optimal cytoreduction are the main goals of surgical therapy.
In a 2003 study, Uygun et al showed a definite survival benefit for patients with lower-stage tumors and for patients who had no residual disease at surgery (mean 108 mo) versus those with residual disease at the end of surgery (mean 42 mo, p = 0.001).
Prepare patients for the possibility of bowel resection and/or ostomy placement if diffuse spread is suggested following the preoperative assessment. A mechanical bowel preparation, with or without antibiotics, should be used in all patients undergoing surgery for a pelvic mass.
Complete surgical staging consists of a thorough examination of the pelvic and intra-abdominal structures. If disease is identified outside the ovary, optimal debulking so that all remaining tumor nodules are smaller than 1 cm improves overall survival and decreases recurrences.
In younger patients who desire future fertility, a unilateral salpingo-oophorectomy almost always provides sufficient treatment because most of these tumors are stage I (see Staging).
Staging should be performed and consists of pelvic washings, selective pelvic and periaortic lymph node sampling on the ipsilateral side, peritoneal biopsies, partial omentectomy, and biopsy of the contralateral ovary (only if it appears abnormal). Previously, biopsy of the contralateral ovary was considered a routine part of the staging procedure but now is not required because only approximately 2% of tumors are bilateral.
Because hormone overproduction is common with GCTs, dilatation and curettage should be considered to help rule out a neoplastic process of the endometrium in younger patients undergoing fertility-sparing surgery, especially if abnormal uterine bleeding was part of their clinical presentation.
For patients in whom future fertility is not a concern, surgical therapy should consist of bilateral salpingo-oophorectomy and total abdominal hysterectomy, in addition to the staging procedures.
Treatment of recurrent GCTs is not as uniform as it is for the primary tumors. Surgical debulking can be of value if the tumor appears to be focal on imaging studies. Chemotherapy, radiotherapy, and hormonal treatments have been used with variable success. All appear to have some benefit for improving long-term survival and the progression-free interval. Mean survival after a recurrence has been diagnosed is approximately 5 years.
DRUG TREATMENT : Surgical treatment is considered first-line therapy for patients with GCTs. Chemotherapy can be used as adjuvant therapy in patients with advanced or recurrent disease and has been effective for improving the disease-free survival. The rarity of this tumor has precluded randomized control trials; therefore, no prospective data are available regarding overall survival in high-risk patients who receive adjuvant chemotherapy compared to those who have not.
The optimal chemotherapy regimen has been hard to identify given that the overall incidence of GCTs is relatively low. Various chemotherapy regimens have been used in patients with GCTs, with varying toxicity and response rates.
Single-agent chemotherapy with alkylating agents has been used in patients with GCTs with only modest partial response rates. Current chemotherapy regimens usually consist of multidrug regimens and most commonly include platinum as one of their agents.
Cisplatin, vinblastine, and bleomycin regimen
The cisplatin (Platinol), vinblastine, and bleomycin (PVB) regimen has been studied most recently and shows moderately high response rates. Pecorelli et al showed complete and partial response rates of 28% and 24%, respectively, with 25.4-month median survival in patients who had not received prior chemotherapy or radiation. An additional 13 patients in their study received prior radiation. Their complete, partial, and overall response rates were 38%, 38%, and 77%, respectively. Median survival in this group was 41.1 months. Hematologic toxicity, nausea, vomiting, and peripheral neuropathy were common, and pulmonary toxicity due to bleomycin was observed in a few patients. Earlier studies by Zambetti et al and Columbo et al showed similar response rates but with severe bone marrow and pulmonary toxicity.
The PVB regimen is cisplatin at 20 mg/m2/d IV for 5 days q3wk for 3-4 courses; bleomycin at 20 U/m2 (not to exceed 30 U) IV qwk for 7 courses, followed by an eighth course during the 10th week; and vinblastine at 12 mg/m2 IV q3wk for 3-4 courses.
Bleomycin, etoposide, and cisplatin regimen
Bleomycin, etoposide, and cisplatin (BEP) regimen also has been studied in patients with advanced and recurrent GCTs. In 1999, Homesley et al reported the Gynecologic Oncology Group's experience using this regimen and included patients with all types of ovarian sex cordβstromal tumors, although 48 patients had GCTs. Patients with gross residual disease, positive findings on peritoneal cytology, and recurrent tumors were included.
Of patients undergoing second-look surgery, 37% (14 of 38) had a pathologic complete response. Additionally, 40% of the 25 patients with measurable disease had an objective response to this regimen. No recurrence or progression of disease was observed in 68% and 51% of patients with primary and recurrent disease, respectively. However, only half the patients had follow-up of 3 years or longer. Only measurable disease was found to be a predictor of both overall survival and progression-free interval. Again, significant toxicity was noted, with bone marrow suppression being most common (79%), followed by GI toxicity.
The BEP regimen is bleomycin at 20 U/m2 (not to exceed 30 U) IV q3wk for 4 courses, etoposide at 75 mg/m2 IV on days 1-5 q3wk for 4 courses, and cisplatin at 20 mg/m2 IV on days 1-5 q3wk for 4 courses.
Older multidrug regimens included (1) cyclophosphamide, doxorubicin (Adriamycin), and cisplatin regimen, which includes cyclophosphamide at 500 mg/m2 IV, Adriamycin at 40-50 mg/m2 IV, and cisplatin at 40-50 mg/m2 IV all given q4wk for 4-6 courses; (2) cisplatin and doxorubicin; and (3) cyclophosphamide, actinomycin, and 5-fluorouracil. These regimens have the benefit of fewer and less serious adverse effects. However, response rates often were poorer than for those of the newer cisplatin-based regimens.
Much less information is available for JGCTs with regard to treatment of advanced disease and recurrences. These tumors tend to behave more aggressively, with earlier recurrences and poorer responses to chemotherapeutic agents. Case reports detailing complete responders can be found for patients treated with carboplatin and etoposide; methotrexate, actinomycin D, and chlorambucil; and methotrexate, actinomycin D, and cyclophosphamide. However, long-term survival rates in patients with JGCTs have been disappointing.
Current research includes the activity of taxanes in the treatment of GCTs. A retrospective review from the MD Anderson Cancer Center suggests that response to taxanes with or without platinum may be similar to that of the BEP regimen with less toxicity. Further studies are ongoing.
1. ANTINEOPLASTIC AGENTS :
- CISPLATIN
- VINBLASTINE
- BLEOMYCIN
- CYCLOPHOSPHAMIDE
- DOXORUBICIN
- ACTINOMYCIN D
- 5-FLUOROURACIL
- ETOPOSIDE
2. UROPROTECTIVE AGENTS : Prevention of hemorrhagic cystitis in patients being treated with ifosfamide and cyclophosphamide
- MESNA
3. ANTIEMETICS : Prevention and treatment of nausea and vomiting associated with chemotherapy
- ONDANSETRON
- GRANISETRON
- PALONOSETRON
- DEXAMETHASONE : Used as antiemetic in low doses during chemotherapy. Usually used in multiagent antiemetic regimens with 5HT-3 receptor antagonists