What is the best management approach for a 71‑year‑old woman with advanced high‑grade serous carcinoma of Müllerian origin presenting with extensive peritoneal carcinomatosis and no identifiable primary tumor, who has well‑controlled hypertension, atrial fibrillation, and a prior ischemic stroke?

Management of Advanced High-Grade Serous Carcinoma of Müllerian Origin with Extensive Peritoneal Carcinomatosis

This 71-year-old woman with extensive peritoneal carcinomatosis from high-grade serous carcinoma of Müllerian origin should receive neoadjuvant chemotherapy with carboplatin and paclitaxel for 3-4 cycles, followed by interval cytoreductive surgery if she responds, then completion chemotherapy to 6 total cycles. 1

Rationale for Neoadjuvant Approach Over Primary Surgery

Given the presentation of "innumerable nodules" throughout the peritoneum without an identifiable primary tumor, this represents advanced-stage disease (likely Stage III-IV) where complete cytoreduction to no visible residual disease is highly unlikely at initial surgery. 1

• Neoadjuvant chemotherapy is preferred over primary cytoreductive surgery when complete macroscopic cytoreduction is unlikely due to extensive peritoneal disease. 1
• High-grade serous carcinomas of Müllerian origin (whether from ovary, fallopian tube, or peritoneum) behave identically and follow ovarian cancer treatment patterns, with extensive peritoneal seeding being characteristic. 2, 3
• The goal is to shrink disease burden to make interval surgery feasible with optimal cytoreduction, which directly impacts survival. 1

Specific Treatment Protocol

Initial Chemotherapy Regimen

Carboplatin (AUC 5-6) plus paclitaxel (175 mg/m²) intravenously every 21 days for 3-4 cycles before reassessment. 1

• Carboplatin is specifically preferred over cisplatin in this patient given her history of ischemic stroke, as carboplatin has a more favorable renal and neurotoxicity profile, which is critical in patients with cerebrovascular disease. 1
• This platinum-taxane combination is the standard first-line regimen for high-grade serous carcinoma with response rates of approximately 72% in advanced disease. 4, 5
• The patient's well-controlled atrial fibrillation and hypertension should not preclude chemotherapy administration, though cardiac monitoring during paclitaxel infusions is prudent. 2

Interval Cytoreductive Surgery

After 3-4 cycles of neoadjuvant chemotherapy, if imaging shows response or stable disease, proceed with interval cytoreductive surgery aiming for no visible residual tumor. 1

• Surgery should include total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, peritoneal biopsies, and maximal tumor debulking of all gross disease. 2
• Complete cytoreduction (no visible residual disease) is the surgical goal, as residual disease volume directly impacts survival. 1, 6
• Evaluation by a gynecologic oncologist is mandatory before proceeding with any surgical intervention. 1

Completion Chemotherapy

Complete a total of 6 cycles of carboplatin plus paclitaxel (including the neoadjuvant cycles). 1

• If 4 cycles were given preoperatively, then 2 additional cycles postoperatively complete the regimen. 1
• Six total cycles is the evidence-based standard duration for high-grade serous carcinoma. 1

Essential Diagnostic Testing

Obtain germline and somatic BRCA1/2 testing immediately at diagnosis to guide subsequent maintenance therapy decisions, but do not delay chemotherapy initiation while awaiting results. 1

• BRCA mutation status determines eligibility for PARP inhibitor maintenance therapy (olaparib), which provides approximately 70% improvement in progression-free survival in BRCA-mutated patients who respond to first-line treatment. 1
• CA-125 levels should be monitored to assess treatment response, though imaging remains the primary modality for evaluating disease extent. 1

Critical Considerations for This Patient's Comorbidities

Stroke History and Anticoagulation

• The patient's atrial fibrillation likely requires anticoagulation, which creates bleeding risk during chemotherapy-induced thrombocytopenia. Close hematologic monitoring with platelet counts before each cycle is essential, with chemotherapy dose delays if platelets fall below 100,000/μL. 2
• Coordinate with cardiology regarding anticoagulation management during nadir periods (typically days 10-14 of each cycle). 2

Performance Status Assessment

• Evaluate ECOG performance status, frailty, and nutritional status before initiating treatment, as these factors influence treatment tolerance and surgical candidacy. 1
• Her age (71) and comorbidities require careful assessment but should not automatically exclude aggressive treatment if performance status is good (ECOG 0-1). 1

Alternative Scenario: If Surgery Is Not Feasible

If the patient does not respond to neoadjuvant chemotherapy or remains medically inoperable after reassessment, continue chemotherapy alone without interval surgery. 2

• Some patients with extensive peritoneal carcinomatosis achieve prolonged survival with chemotherapy alone, particularly when platinum-based regimens are used. 6
• The 2-year survival with cisplatin-based therapy (carboplatin is equivalent) in peritoneal carcinomatosis is approximately 47%, compared to 14% with non-platinum regimens. 6

Maintenance Therapy Planning

For BRCA1/2 mutation carriers who achieve complete or partial response, initiate olaparib 300 mg orally twice daily as maintenance therapy after completing 6 cycles of chemotherapy. 1

• This provides substantial progression-free survival benefit in BRCA-mutated patients. 1
• For BRCA wild-type patients, observation with routine surveillance is standard, though clinical trial enrollment should be encouraged. 1

Common Pitfalls to Avoid

• Do not proceed directly to surgery without gynecologic oncology evaluation and consideration of neoadjuvant chemotherapy when extensive peritoneal disease is present, as suboptimal cytoreduction worsens outcomes. 1
• Do not confuse this high-grade serous carcinoma with low-grade serous carcinoma, which has entirely different biology, treatment, and prognosis. 1, 7
• Do not misclassify this as a carcinosarcoma (malignant mixed Müllerian tumor), which would require ifosfamide-based chemotherapy rather than carboplatin-paclitaxel. 2
• Do not delay BRCA testing, as results guide critical maintenance therapy decisions. 1