What are the treatment options for a 25-year-old female with stage III ovarian carcinoma (ovarian cancer) and elevated Cancer Antigen 125 (CA125) levels, who desires fertility preservation?

Treatment Approach for Stage III Ovarian Cancer with Fertility Preservation in a 25-Year-Old

This patient with stage III ovarian cancer should receive neoadjuvant chemotherapy (NACT) with platinum-taxane doublet followed by interval debulking surgery (IDS), and fertility preservation through embryo or oocyte cryopreservation should be pursued before starting chemotherapy, though the advanced stage makes fertility-sparing surgery extremely unlikely to be oncologically appropriate. 1

Critical Reality About Fertility Preservation in Stage III Disease

Fertility-sparing surgery is NOT recommended for stage III ovarian cancer. The evidence-based guidelines are clear:

• Fertility-sparing surgery (unilateral salpingo-oophorectomy with uterine preservation) is only appropriate for stage IA, IB grades 1-2, and selected IC1 disease 1, 2
• Stage III disease requires bilateral salpingo-oophorectomy (BSO), total hysterectomy, complete infragastric omentectomy, and appendicectomy as standard treatment 1
• The goal in stage III disease is maximal cytoreduction with complete or optimal tumor resection, which is incompatible with preserving reproductive organs 1

Fertility Preservation Options Before Chemotherapy

Before initiating chemotherapy, offer embryo or oocyte cryopreservation (not ovarian tissue cryopreservation, which carries risk of reintroducing malignant cells): 1, 2

• Embryo cryopreservation (requires partner or donor sperm): Most established technique with highest success rates 1

  • Requires 10-14 days of ovarian stimulation from beginning of menstrual cycle 1
  • For hormone-sensitive tumors, use letrozole or tamoxifen concurrent with FSH to minimize estrogen exposure 1
  • Cost approximately $8,000 per cycle plus $350/year storage 1
  • This will delay chemotherapy by 2-6 weeks depending on menstrual cycle timing 1

• Oocyte cryopreservation (no partner required): Less established but viable option 1

  • Same stimulation protocol and timeline as embryo cryopreservation 1
  • Lower success rates: approximately 2% live births per thawed oocyte (3-4 times lower than standard IVF) 1

Recommended Chemotherapy Approach

Initiate neoadjuvant chemotherapy with platinum-taxane doublet for 3 cycles, followed by interval debulking surgery, then 3 additional cycles (total 6 cycles): 1

Specific Chemotherapy Regimen

• Carboplatin (AUC 5-6) + Paclitaxel (175 mg/m²) every 3 weeks 1, 3, 4
• Alternative: Carboplatin 300 mg/m² + Cyclophosphamide 600 mg/m² every 4 weeks 3
• Platinum-taxane doublet is the recommended NACT regimen for high-grade serous or endometrioid ovarian cancer 1

Rationale for NACT Approach in This Patient

NACT followed by IDS is appropriate for stage III disease with high tumor burden: 1

• The 2025 ASCO guideline establishes NACT as non-inferior to primary debulking surgery (PDS) for stage III/IV disease 1
• NACT achieves higher complete resection rates (80.6% vs 41.6% with PDS) in extensive disease 5
• Lower postoperative morbidity and mortality compared to PDS 1, 5
• Median survival 42 months vs 23 months in patients with poor prognostic features when treated with NACT vs PDS 6

Monitoring Response to NACT

Measure CA-125 before each chemotherapy cycle: 1

• CA-125 levels correlate with tumor response and survival 1
• Target: CA-125 normalization (≤35 U/mL) before IDS - this is associated with improved survival 7
• A CA-125 ≤30 U/mL before surgery predicts higher likelihood of complete resection 8
• Perform CT scan after 3 cycles to assess resectability 1

Timing of Interval Debulking Surgery

Perform IDS after 3 cycles of NACT if: 1

• Good response to chemotherapy (stable disease or better) 1
• CA-125 normalized or significantly decreased 8, 7
• Imaging suggests resectable disease 1

Consider additional 3 cycles before surgery (total 6 cycles NACT) if: 8

• CA-125 remains elevated (>30-35 U/mL) 8
• Imaging suggests complete resection unlikely 8
• This approach shows equivalent survival to standard 3+3 approach 8

Surgical Goals at Interval Debulking

The objective is complete resection of all macroscopic disease (R0 resection): 1, 5

• Complete resection is the strongest independent predictor of overall survival 1, 5
• Standard surgery includes: BSO, total hysterectomy, complete omentectomy, appendicectomy, pelvic and para-aortic lymphadenectomy if indicated 1
• HIPEC may be offered during IDS for stage III disease in patients with good performance status through shared decision-making 1

Post-Surgical Chemotherapy

Complete total of 6 cycles (NACT + post-IDS chemotherapy): 1

• Continue same platinum-taxane regimen 1
• May adjust based on individual patient factors and response 1

Future Fertility Considerations

If uterus is preserved (highly unlikely in stage III): 2

• Pregnancy through egg donation could theoretically be considered if bilateral oophorectomy performed but uterus conserved 2
• However, this is NOT standard for stage III disease 1

Critical Pitfalls to Avoid

• Do not delay chemotherapy >2-6 weeks for fertility preservation - this is advanced cancer requiring prompt treatment 1
• Do not attempt fertility-sparing surgery in stage III disease - this compromises oncologic outcomes 1, 2
• Do not proceed to IDS if CA-125 remains significantly elevated - consider additional chemotherapy cycles 8, 7
• Do not use ovarian tissue cryopreservation - risk of reintroducing malignant cells 2
• Ensure complete surgical staging and maximal cytoreduction - residual disease is the most important negative prognostic factor 1, 5

Genetic Testing

Perform germline BRCA1, BRCA2, and other ovarian cancer susceptibility gene testing: 1

• Results will guide maintenance therapy decisions (PARP inhibitors) 1
• Important for family counseling 1