Management of Granulosa Cell Tumor of the Ovary
Surgical Management: The Cornerstone of Treatment
For stage IA adult granulosa cell tumors, surgery alone is curative and no adjuvant therapy is required. 1, 2, 3
Fertility-Sparing Surgery (Premenopausal/Reproductive Age)
- Unilateral salpingo-oophorectomy with preservation of the contralateral ovary and uterus is the standard surgical approach for young patients desiring fertility, even in advanced disease due to high chemosensitivity 1, 3
- No systematic biopsy of the contralateral ovary is necessary when it appears macroscopically normal 1, 3
- Mandatory endometrial curettage must be performed to rule out concomitant uterine cancers, as granulosa cell tumors produce estrogen that can stimulate the endometrium 1, 3
- Retroperitoneal lymph node dissection is not mandatory due to very low incidence of retroperitoneal metastases in early-stage disease 1, 3
Complete Staging Procedure
The surgical staging should include: 1, 3
- Careful examination of the entire abdominal cavity
- Peritoneal washings for cytology
- Infracolic omentectomy
- Biopsy of diaphragmatic peritoneum, paracolic gutters, and pelvic peritoneum
- Lymph node dissection only if nodes appear abnormal
Postmenopausal or Advanced Disease Surgery
- Total abdominal hysterectomy and bilateral salpingo-oophorectomy with complete surgical staging for postmenopausal women or bilateral ovarian involvement 1
- For advanced disease, perform debulking surgery to remove as much gross tumor as possible, but avoid ultraradical extensive procedures given high chemosensitivity 1, 3
Adjuvant Chemotherapy: When to Use It
Early Stage Disease (Stage IA)
- Stage IA adult granulosa cell tumors require NO adjuvant therapy after surgery alone - they have excellent prognosis 1, 2, 3
- For stage IC patients with high mitotic index, adjuvant therapy should be considered 1, 3
Advanced Stage Disease (Stage IIb-IV)
Platinum-based chemotherapy is the treatment of choice for advanced-stage disease: 1, 3
- BEP regimen (bleomycin, etoposide, cisplatin) is the most widely used 1, 3
- Three cycles of BEP for completely resected disease 1, 3
- Four to five cycles for macroscopic residual disease (omit bleomycin to reduce lung toxicity risk) 1
- Overall response rate of 63-80% with platinum-based chemotherapy 1
Recurrent Disease Management
Debulking surgery remains the most effective treatment for recurrent disease when feasible. 1, 2, 3
Chemotherapy for Recurrence
- Platinum-sensitive relapse (>6 months disease-free interval): Use platinum-based combinations 1, 3
- Platinum-resistant disease: Consider VAC (vincristine, actinomycin D, cyclophosphamide) or paclitaxel-gemcitabine as salvage therapy 1, 3
- Taxanes have demonstrated interesting activity with favorable toxicity profile 1
Hormonal Therapy for Recurrence
Hormone therapy should be reserved specifically for patients with recurrent disease who have failed or are not candidates for surgery and chemotherapy: 2
- Aromatase inhibitors (letrozole) have shown responses in recurrent disease 2
- Tamoxifen has documented responses 2
- Progestins have shown activity 2
Critical pitfall: Do not use hormone therapy as primary treatment for early-stage disease or substitute it for platinum-based chemotherapy in treatment-naive advanced disease 2
Surveillance and Follow-Up
Long-term surveillance is mandatory as recurrences can occur up to 20-25 years after primary diagnosis. 2, 3, 4
Surveillance Schedule
- Every 3 months for the first 2 years: History, physical examination with pelvic exam, tumor markers 3
- Every 6 months during years 3-5 3
- Continue extended follow-up beyond 5 years given late recurrence pattern 2, 3, 4
Monitoring Tools
- Inhibin B levels (most sensitive marker if initially elevated) 2, 3, 5
- Additional markers: estradiol, AMH 3
- Pelvic ultrasound and CT abdomen/pelvis every 3-6 months 2, 3
- Chest imaging as clinically indicated 3