What is the optimal treatment approach for a 71‑year‑old woman with high‑grade serous carcinoma of Müllerian origin and extensive peritoneal implants, who has well‑controlled hypertension and a prior ischemic stroke?

Treatment of High-Grade Serous Carcinoma with Peritoneal Spread in a 71-Year-Old Woman

This patient should undergo evaluation by a gynecologic oncologist to determine if primary cytoreductive surgery is feasible; if complete cytoreduction appears achievable based on imaging and performance status, proceed with primary debulking surgery followed by carboplatin plus paclitaxel chemotherapy for 6 cycles, but if complete cytoreduction is unlikely or the patient has significant comorbidities limiting surgical candidacy, initiate neoadjuvant chemotherapy with carboplatin plus paclitaxel for 3-4 cycles followed by interval debulking surgery. 1

Initial Assessment and Risk Stratification

The first critical step is comprehensive evaluation by a gynecologic oncologist to assess surgical candidacy 1. This assessment must evaluate:

• Performance status (ECOG): Given her age (71) and history of ischemic stroke, functional status is paramount 1
• Disease resectability: The CT scan showing "innumerable tumor nodules" suggests extensive peritoneal disease, which raises concern about achieving complete cytoreduction 1
• Comorbidity burden: Well-controlled hypertension is manageable, but prior stroke requires careful consideration of surgical risk and anesthetic tolerance 1

BRCA1/2 germline and somatic testing should be initiated immediately at diagnosis, as this will inform maintenance therapy options after completing primary treatment 2, 1. Testing should not delay chemotherapy initiation 2.

Treatment Algorithm Based on Surgical Candidacy

Scenario 1: If Complete Cytoreduction Appears Achievable

Primary cytoreductive surgery is preferred over neoadjuvant chemotherapy when there is high likelihood of achieving complete macroscopic resection (no visible residual disease) 1. However, given the CT description of "innumerable tumor nodules," this scenario is less likely unless imaging suggests disease is confined to resectable areas.

Following surgery, administer:

• Carboplatin (AUC 5-6) plus paclitaxel (175 mg/m²) intravenously every 21 days for 6 cycles 1, 2
• This is the standard adjuvant regimen for advanced high-grade serous carcinoma 1

Scenario 2: If Complete Cytoreduction Is Unlikely (More Probable Given Clinical Picture)

Neoadjuvant chemotherapy followed by interval debulking surgery is recommended when complete cytoreduction appears unlikely based on extensive peritoneal disease 1. This approach is particularly appropriate given:

• Extensive peritoneal implants ("innumerable nodules") 1
• Age 71 with stroke history, making prolonged complex surgery higher risk 1
• Need to assess chemotherapy response before committing to major surgery 1

Treatment sequence:

1. Neoadjuvant chemotherapy: Carboplatin (AUC 5-6) plus paclitaxel (175 mg/m²) IV every 21 days for 3-4 cycles 1

   • Assess response with CA-125 levels and repeat imaging after 3 cycles 1

2. Interval cytoreductive surgery after ≤4 cycles if response or stable disease 1

   • Goal remains complete macroscopic resection 1
   • Surgery should not be delayed beyond 4 cycles of NACT 1

3. Completion chemotherapy to total 6 cycles (including pre-operative cycles) 1

Special Considerations for This Patient's Comorbidities

Stroke History

• Carboplatin has lower nephrotoxicity and neurotoxicity compared to cisplatin, making it preferable 2
• Monitor for thromboembolic events, as platinum-based chemotherapy increases VTE risk 3
• Consider prophylactic anticoagulation discussion with oncology and neurology teams

Hypertension

• Bevacizumab is FDA-approved for platinum-resistant recurrent ovarian cancer 4 and has been studied in first-line treatment 3, but it significantly increases hypertension risk and carries GI perforation risk
• Given her well-controlled hypertension and extensive peritoneal disease (higher perforation risk), bevacizumab should NOT be added to first-line therapy in this patient 3
• The 2010 phase II study showed 2 GI perforations in 62 patients during chemotherapy phase 3, and extensive peritoneal disease increases this risk

Maintenance Therapy Considerations

If BRCA1/2 mutation is identified (germline or somatic) and the patient achieves complete or partial response after completing primary treatment:

• Olaparib 300 mg orally twice daily as maintenance therapy is recommended 2
• This applies whether she received primary debulking or neoadjuvant chemotherapy followed by interval surgery 2
• SOLO-1 trial showed 70% improvement in progression-free survival with olaparib maintenance in BRCA-mutated patients 2
• Continue until disease progression or unacceptable toxicity 2

If no BRCA mutation is identified:

• Observation with surveillance is standard 2
• Clinical trial enrollment should be considered 2

Critical Pitfalls to Avoid

• Do not proceed with neoadjuvant chemotherapy without gynecologic oncologist evaluation first 1 - surgical candidacy assessment is mandatory
• Do not confuse high-grade serous carcinoma with low-grade serous carcinoma 1 - they have completely different biology and treatment approaches
• Do not delay BRCA testing 2 - it should be initiated at diagnosis, though chemotherapy should not be delayed for results
• Do not add bevacizumab to first-line therapy in this patient given stroke history, hypertension, and extensive peritoneal disease increasing perforation risk 3
• Do not perform suboptimal cytoreductive surgery 1 - if complete resection is not achievable, neoadjuvant chemotherapy is preferred

Prognosis Discussion

Approximately 70% of high-grade serous ovarian cancers are diagnosed at advanced stage 5. Prognosis depends critically on achieving complete macroscopic resection 5. With extensive peritoneal disease as described, even with optimal treatment:

• If platinum-sensitive disease: median survival extends beyond 3 years with modern therapy 5
• If platinum-resistant disease develops (progression within 6 months): median survival is 9-14 months from recurrence 5
• Complete cytoreduction remains the most important modifiable prognostic factor 5

Early integration of palliative care is recommended to improve quality of life, focusing on symptom control including pain, nausea, and ascites management 5. This should occur concurrently with systemic therapy 5.