What is the recommended adjuvant treatment for sex cord (gonadal stromal) malignant tumors?

Adjuvant Treatment for Sex Cord-Stromal Tumors

For early-stage (FIGO stage I) sex cord-stromal tumors, observation is the preferred approach after complete surgical staging, with adjuvant platinum-based chemotherapy (BEP regimen for 3-6 cycles) reserved only for high-risk features including stage IC, high mitotic index, poor differentiation, or tumor rupture. 1

Early-Stage Disease (FIGO Stage I-IIA)

Standard Management

• Most patients (60-95%) present with stage I disease and have excellent prognosis (90% long-term disease-free survival) with surgery alone 1
• The benefit of adjuvant chemotherapy in early-stage disease remains unproven and controversial 1
• Recent high-quality evidence from a multicentric study of 469 patients demonstrated that chemotherapy had no impact on progression-free survival in early-stage (FIGO I-II) disease 2

High-Risk Features Warranting Adjuvant Therapy

Consider adjuvant platinum-based chemotherapy for: 1, 3

• Stage IC disease (tumor rupture, surface involvement, or positive washings)
• High mitotic index
• Poor differentiation (Grade 3)
• Tumor size >10-15 cm
• Presence of heterologous elements or retiform pattern (particularly in Sertoli-Leydig tumors) 3, 4

Recommended Chemotherapy Regimen

BEP (bleomycin, etoposide, cisplatin) for 3-6 cycles is the standard regimen 1, 3

Alternative platinum-based regimens if BEP is contraindicated: 1, 3

• Paclitaxel/carboplatin (preferred alternative)
• Etoposide/cisplatin (EP) for 4 cycles
• Avoid bleomycin in patients >40 years or with pre-existing pulmonary disease 4

Advanced-Stage Disease (FIGO Stage IIB-IV)

Primary Treatment Approach

• Debulking surgery remains the most effective treatment for metastatic or recurrent disease 1
• Complete surgical resection is the strongest predictor of progression-free survival across all treatment lines 2

Adjuvant Chemotherapy

Platinum-based chemotherapy is recommended for all patients with advanced-stage disease: 1

• BEP regimen for 3-6 cycles (preferred)
• Overall response rate: 63-80% 1
• Three cycles for completely resected disease; four cycles for macroscopic residual disease 1

Alternative Regimens

• Paclitaxel/carboplatin - demonstrated interesting activity with favorable toxicity profile 1
• Taxane and platinum combinations are reasonable candidates for future trials 1

Critical Evidence Considerations

Surgery vs. Chemotherapy Impact

A 2023 multicentric study (469 patients, 6.4-year median follow-up) provides the most robust recent evidence: 2

• Only surgery quality demonstrated benefit for progression-free survival
• Chemotherapy use did not impact survival in first-line or relapse settings
• This applies across all treatment lines, including recurrent disease

Chemotherapy Efficacy by Tumor Subtype

• Granulosa cell tumors: Platinum-based regimens show 63-80% response rates 1
• Sertoli-Leydig tumors: Limited data, but responses reported with BEP regimen 1
• Pediatric studies show VIP (etoposide, ifosfamide, cisplatin) effectively prevents recurrences in tumor rupture cases 5

Radiation and Hormonal Therapy

Little evidence exists for radiation therapy or hormonal therapy; these should be restricted to highly selected cases only 1

Common Clinical Pitfalls to Avoid

Do NOT:

• Perform radical surgery (bilateral salpingo-oophorectomy with hysterectomy) in reproductive-age patients with stage I disease - compromises fertility without improving outcomes 3, 4
• Routinely administer adjuvant chemotherapy for stage IA well-differentiated tumors without high-risk features - no evidence of benefit 1, 4, 2
• Perform systematic lymphadenectomy - very low incidence of retroperitoneal metastases in early-stage disease; adds morbidity without benefit 3, 4
• Discontinue follow-up prematurely - relapses can occur >20 years (up to 37 years) after diagnosis 1, 4

Surveillance Strategy

Follow-Up Schedule

Long-term surveillance is mandatory due to indolent nature and late recurrence risk: 1

• Every 3 months for first 2 years: history, physical examination, pelvic examination, tumor markers
• Every 6 months for years 3-5: same assessments
• Pelvic ultrasound every 6 months for fertility-sparing surgery patients 1, 3
• CT abdomen/pelvis yearly or according to clinical indication 1

Tumor Markers

• Inhibin levels can be followed if initially elevated (particularly for granulosa cell tumors) 1
• CA125 may be useful in some cases 1
• Testosterone levels if initially elevated (Sertoli-Leydig tumors) 4

Recurrence Patterns

• Median time to relapse: 4-6 years 1
• Common sites: upper abdomen (55-70%), pelvis (30-45%) 1
• Recurrences reported up to 37 years post-diagnosis 1