What is the standard treatment for a patient diagnosed with high-grade serous ovarian cancer?

Standard Treatment for High-Grade Serous Ovarian Cancer

For patients with high-grade serous ovarian cancer, the standard treatment consists of primary cytoreductive surgery performed by a gynecologic oncologist followed by six cycles of carboplatin plus paclitaxel chemotherapy, with consideration of maintenance therapy using bevacizumab and/or PARP inhibitors based on BRCA/HRD status. 1

Initial Assessment and Surgical Candidacy

Before initiating any treatment, every patient must undergo evaluation by a fellowship-trained gynecologic oncologist to determine surgical candidacy 1. This assessment includes:

• Performance status evaluation: ECOG performance status, age, frailty status, nutritional status, and comorbidities 1
• Disease resectability assessment: Based on CT chest/abdomen/pelvis imaging and clinical examination 1
• Tumor marker measurement: CA-125 levels 1
• Genetic testing: Germline and somatic BRCA1/2 and homologous recombination deficiency testing at diagnosis 1

Treatment Algorithm Based on Surgical Candidacy

For Patients Fit for Surgery with High Likelihood of Complete Cytoreduction

Primary cytoreductive surgery is the preferred initial approach over neoadjuvant chemotherapy 1. The surgical procedure includes:

• Total abdominal hysterectomy and bilateral salpingo-oophorectomy 2
• Complete infragastric omentectomy 2
• Systematic pelvic and para-aortic lymphadenectomy 2
• Peritoneal washing with cytological examination 2
• Biopsies from all visible lesions and all abdominal fields 2
• Resection of all visible disease to achieve complete cytoreduction 2

The goal is complete cytoreduction (no residual disease), as this provides the best chance for prolonged survival 2. If standard surgery cannot achieve complete or optimal resection, additional interventions may include excision of the entire genital tract, bowel resection, and excision of peritoneal metastases 2.

Following surgery, patients receive carboplatin plus paclitaxel for 6 cycles 1, 3. The standard dosing is carboplatin AUC 5-6 plus paclitaxel 175 mg/m² every 3 weeks 3, 4.

For Patients Unlikely to Achieve Complete Cytoreduction

Neoadjuvant chemotherapy is recommended over primary surgery for patients with bulky stage III-IV disease who are not optimal surgical candidates 1, 2. The treatment sequence is:

1. Neoadjuvant chemotherapy: Carboplatin plus paclitaxel for ≤4 cycles 1
2. Interval cytoreductive surgery: Performed after demonstrating response or stable disease 1
3. Completion chemotherapy: To complete 6 total cycles 1

Critical pitfall: Do not proceed with neoadjuvant chemotherapy without gynecologic oncologist evaluation, as many patients initially deemed inoperable can achieve complete cytoreduction with primary surgery 1.

Early-Stage Disease (Stage I-II)

For the minority of patients diagnosed with early-stage high-grade serous carcinoma:

• Complete surgical staging is mandatory, including all components listed above 2
• Adjuvant chemotherapy with carboplatin plus paclitaxel for 6 cycles is required even for early-stage disease 1, 2

This differs critically from low-grade histologies where observation may be appropriate for stage IA/IB disease 5. Do not omit adjuvant chemotherapy for early-stage high-grade serous carcinoma 1.

Maintenance Therapy

After completion of initial chemotherapy, maintenance therapy should be considered based on molecular characteristics:

• BRCA-mutated or HRD-positive tumors: PARP inhibitor maintenance therapy significantly improves progression-free survival and overall survival, with 5-year overall survival rates of approximately 70% 6
• All patients with advanced disease: Bevacizumab maintenance may be added to improve outcomes 6, 7

Important Distinctions and Pitfalls

Do Not Confuse with Low-Grade Serous Carcinoma

High-grade serous carcinoma is chemosensitive and requires platinum-based chemotherapy 1. This contrasts sharply with low-grade serous carcinoma, which is inherently chemoresistant and where surgery is the single most critical intervention 5. Low-grade disease may be managed with observation for stage IA/IB or hormonal therapy for recurrence 5.

Fertility-Sparing Surgery is NOT Appropriate

Fertility-sparing surgery is generally contraindicated for high-grade serous carcinoma 2, unlike low-grade histologies where unilateral salpingo-oophorectomy may be considered for stage IA disease 2.

Chemotherapy Dosing Considerations

For patients with impaired renal function (creatinine clearance <60 mL/min), carboplatin dosing must be adjusted 3:

• CrCl 41-59 mL/min: 250 mg/m² 3
• CrCl 16-40 mL/min: 200 mg/m² 3

Alternatively, the Calvert formula can be used: Total Dose (mg) = (target AUC) × (GFR + 25) 3.

Prognosis and Recurrence

Despite an initial response rate of approximately 80%, most patients with advanced-stage disease (75-80%) will experience recurrence within 2 years 6, 8. The 5-year overall survival for advanced-stage disease is 10-40% overall, but improves to approximately 70% for BRCA-mutated patients receiving PARP inhibitor maintenance 6. Early-stage disease has a 5-year overall survival of 70-95% 6.

The emergence of platinum resistance is the primary reason for treatment failure 8, emphasizing the importance of complete initial cytoreduction and appropriate use of maintenance therapies to delay recurrence.