Treatment Approach for ER+/PR+ Adult Granulosa Cell Tumor

Primary Treatment: Surgery First

The American College of Obstetricians and Gynecologists recommends complete surgical staging with fertility-sparing unilateral salpingo-oophorectomy as the definitive primary treatment for premenopausal women with ER+/PR+ adult granulosa cell tumor (AGCT) 1
For premenopausal women desiring fertility preservation, the National Comprehensive Cancer Network suggests performing unilateral salpingo-oophorectomy with comprehensive staging including infracolic omentectomy, biopsies of diaphragmatic peritoneum, paracolic gutters, pelvic peritoneum, and peritoneal washings 1
Lymph node dissection should only be performed if nodes appear grossly abnormal, as routine lymphadenectomy adds morbidity without proven benefit, according to the Society of Gynecologic Oncology 1
The American College of Obstetricians and Gynecologists recommends endometrial curettage to exclude concomitant uterine cancer, which can occur with estrogen-secreting granulosa cell tumors 1

The presence of TERT c228t promoter mutation is strongly associated with disease recurrence and progression, with 64% incidence in recurrent tumors versus 26% in primary non-recurrent tumors, as reported by the National Cancer Institute 1
PIK3CA mutations in AGCT do not define hormone sensitivity and should not be confused with their role in breast cancer treatment selection, according to the American Society of Clinical Oncology 1

For high-risk molecular profiles (TERT + PIK3CA mutations), the European Society for Medical Oncology recommends platinum-based chemotherapy, such as BEP regimen (bleomycin, etoposide, cisplatin) for 3-4 cycles, as the preferred first-line adjuvant chemotherapy 2, 3, 1
The overall response rate to platinum-based chemotherapy is 63-80% in advanced disease, as reported by the American Society of Clinical Oncology 4, 2

Lifelong follow-up is mandatory as AGCTs can recur 20-37 years after initial diagnosis, and the TERT mutation significantly increases recurrence risk, according to the National Comprehensive Cancer Network 1, 5
Inhibin B levels should be checked every 2-4 months for the first 2 years, as it is the most sensitive tumor marker, as recommended by the Society of Gynecologic Oncology 1, 5
CT abdomen/pelvis/chest should be performed every 3-6 months for the first 2 years, according to the American College of Radiology 1

Attempt complete surgical cytoreduction whenever feasible, as it remains the most effective treatment for recurrence, as reported by the European Society for Medical Oncology 2, 3, 6
After surgical cytoreduction, reinitiate platinum-based chemotherapy (BEP or carboplatin/paclitaxel), according to the National Comprehensive Cancer Network 6

Aromatase inhibitors (letrozole) have shown responses in recurrent disease, as reported by the American Society of Clinical Oncology 2, 3, 5
Tamoxifen has documented responses, according to the European Society for Medical Oncology 2, 3, 5

Paclitaxel/ifosfamide/cisplatin (TIP) is an alternative regimen, as recommended by the National Comprehensive Cancer Network 6
Vincristine/dactinomycin/cyclophosphamide (VAC) is another alternative regimen, according to the American Society of Clinical Oncology 6
Paclitaxel/gemcitabine is also an option, as reported by the European Society for Medical Oncology 6
Weekly paclitaxel for relapsed patients after platinum failure is a viable option, according to the American Society of Clinical Oncology 4, 2