Treatment of High-Grade Ovarian Serous Carcinoma
For high-grade serous ovarian carcinoma, treatment consists of maximal cytoreductive surgery performed by a gynecologic oncologist followed by platinum-taxane combination chemotherapy (carboplatin plus paclitaxel) for 6 cycles, with consideration of neoadjuvant chemotherapy for patients unlikely to achieve complete cytoreduction or those with high perioperative risk. 1
Initial Assessment and Surgical Planning
Before initiating treatment, evaluation by a gynecologic oncologist is mandatory to determine surgical candidacy 1. The assessment should evaluate:
- Patient fitness factors: ECOG performance status, age, frailty status, nutritional status, and comorbidities 1
- Disease resectability: Likelihood of achieving complete cytoreduction (no visible residual disease) based on imaging and clinical examination 1
- Imaging: CT chest/abdomen/pelvis to assess disease extent 1
- Tumor markers: CA-125 levels 1
- Genetic testing: Germline and somatic testing for BRCA1/2 and homologous recombination deficiency should occur at diagnosis 1
Diagnostic confirmation: Core biopsy is strongly preferred before neoadjuvant chemotherapy; cytology with CA-125:CEA ratio >25 is acceptable only when biopsy cannot be performed 1
Treatment Algorithm by Clinical Scenario
For Patients Fit for Surgery with High Likelihood of Complete Cytoreduction
Primary cytoreductive surgery (PCS) is recommended over neoadjuvant chemotherapy 1. Surgery should include:
- Total abdominal hysterectomy 1
- Bilateral salpingo-oophorectomy 1
- Omentectomy 1
- Systematic pelvic and para-aortic lymphadenectomy 1
- Peritoneal biopsies and cytological washings 1
- Resection of all visible disease to achieve complete cytoreduction 1
Post-surgical chemotherapy: Following PCS, administer carboplatin plus paclitaxel for 6 cycles 1, 2. The 2025 ASCO guideline and multiple consensus statements establish this platinum-taxane doublet as the standard regimen for high-grade serous histology 1.
For Patients Unlikely to Achieve Complete Cytoreduction
Neoadjuvant chemotherapy (NACT) is recommended over primary surgery when a gynecologic oncologist determines complete cytoreduction is unlikely 1. This approach involves:
- NACT regimen: Carboplatin plus paclitaxel (platinum-taxane doublet) 1
- Interval cytoreductive surgery (ICS): Perform after ≤4 cycles of NACT in patients with response or stable disease 1
- Completion chemotherapy: Continue carboplatin plus paclitaxel to complete 6 total cycles 1
HIPEC consideration: For FIGO stage III disease patients with good performance status and adequate renal function treated with NACT, hyperthermic intraperitoneal chemotherapy (HIPEC) may be offered at interval cytoreductive surgery 1
For Patients with High Perioperative Risk
Patients with poor performance status, significant frailty, or high surgical risk should receive NACT 1. The decision to defer surgery must be made in consultation with a gynecologic oncologist 1.
Early-Stage Disease (Stage I-II)
For the minority of patients diagnosed with early-stage high-grade serous carcinoma:
- Complete surgical staging is essential, including all components listed above 1
- Adjuvant chemotherapy: Carboplatin plus paclitaxel for 6 cycles is recommended for all high-grade serous carcinomas regardless of stage 1
- Stage IA/IB: Even early-stage high-grade serous requires adjuvant chemotherapy due to aggressive biology 1
Fertility-Sparing Considerations
Fertility-sparing surgery is generally NOT appropriate for high-grade serous carcinoma due to its aggressive nature and typical bilateral involvement 1. The 2024 ESGO-ESMO consensus recommendations for fertility preservation apply primarily to borderline tumors, low-grade histologies, and select early-stage malignancies—not high-grade serous carcinoma 1.
Chemotherapy Dosing and Administration
Standard regimen 2:
- Carboplatin: 360 mg/m² IV every 4 weeks OR AUC-based dosing using Calvert formula
- Paclitaxel: Combined with carboplatin per standard protocols
- Duration: 6 cycles total 1
Dose adjustments: Required for renal impairment (creatinine clearance <60 mL/min) and hematologic toxicity 2. For creatinine clearance 41-59 mL/min, reduce carboplatin to 250 mg/m²; for 16-40 mL/min, reduce to 200 mg/m² 2.
Critical Pitfalls to Avoid
Do not proceed with neoadjuvant chemotherapy without gynecologic oncologist evaluation 1. Published data demonstrate survival advantage when gynecologic oncologists perform primary assessment and surgery 1.
Do not confuse high-grade serous with low-grade serous carcinoma. Low-grade serous is relatively chemotherapy-resistant and may be considered for hormonal therapy; high-grade serous requires platinum-taxane chemotherapy 1.
Do not omit adjuvant chemotherapy for early-stage high-grade serous carcinoma. Unlike some other histologies where observation may be appropriate for stage IA/IB disease, high-grade serous requires chemotherapy at all stages 1.
Do not use aluminum-containing needles or IV sets with carboplatin, as aluminum causes precipitate formation and loss of potency 2.
Maintenance Therapy Considerations
While not detailed in the provided early-stage guidelines, the 2025 JAMA review notes that most patients with advanced-stage disease receive maintenance therapy with bevacizumab and/or PARP inhibitors following completion of primary chemotherapy 3. This is particularly relevant for BRCA-mutated tumors, where PARP inhibitors significantly improve outcomes 3.