What is the initial step in managing a patient with high-grade serous ovarian cancer, including staging and treatment?

High-Grade Serous Ovarian Cancer Staging and Initial Management

All patients with high-grade serous ovarian cancer should undergo surgical staging according to the 2014 FIGO staging system, with comprehensive surgical cytoreduction performed by a gynecologic oncologist, followed by molecular testing for BRCA1/2 mutations and homologous recombination deficiency (HRD) at diagnosis. 1

Initial Diagnostic Work-Up

When high-grade serous ovarian cancer is suspected, the following diagnostic steps are essential:

• Serum CA-125 measurement is required, though it is only elevated in approximately 50% of FIGO stage I cases and can be elevated in benign conditions like endometriosis 1
• Pelvic ultrasound (transvaginal and/or transabdominal) by an expert examiner using validated diagnostic models (IOTA Simple Rules or ADNEX model) 1
• CT scan of thorax, abdomen, and pelvis with IV contrast to complete clinical staging and aid surgical planning 1
• Pathological diagnosis must be made according to the 2020 WHO classification by an expert gynecological pathologist 1

Important Imaging Considerations

• CT and PET-CT imaging underestimate bowel or mesenteric involvement compared with surgical exploration 1
• Diffusion-weighted MRI may have better sensitivity than CT for detecting surgically critical tumor sites including mesenteric root infiltration, small bowel and colon carcinomatosis 1
• Extension of tumor from omentum to spleen or liver surface (stage IIIC) must be differentiated from isolated liver or spleen parenchymal metastases (stage IVB) 1

Surgical Staging Requirements

Surgical staging according to the revised 2014 FIGO staging system is mandatory for all patients. 1 The histotype and primary site (ovary, fallopian tube, or peritoneum) must be established and recorded 1

Critical Surgical Components

For comprehensive staging, the following procedures should be performed 1:

• Total abdominal hysterectomy and bilateral salpingo-oophorectomy (unless fertility preservation is indicated in select early-stage cases)
• Aspiration of ascites or peritoneal lavage for cytologic examination 1
• Cytological assessment of pleural fluid if present and safely assessable 1
• Complete omentectomy (removal of all involved omentum) 1
• Bilateral pelvic and para-aortic lymph node dissection for patients with tumor nodules ≤2 cm outside the pelvis (presumed stage IIIB) 1
• Resection of suspicious and/or enlarged nodes when possible 1

Cytoreductive Surgery Goals

Maximal cytoreductive effort should achieve complete resection of all visible disease or residual tumor nodules <1 cm in maximum diameter. 1 There is a strong prognostic link between the degree of post-operative residual disease and patient survival 1

Procedures that may be necessary for optimal cytoreduction include 1:

• Radical pelvic dissection
• Bowel resection and/or appendectomy
• Diaphragm or other peritoneal surface stripping
• Splenectomy
• Partial hepatectomy
• Partial gastrectomy
• Partial cystectomy and/or ureteroneocystostomy

A gynecologic oncologist must perform the primary surgery (category 1 recommendation). 1

Mandatory Molecular Testing

All patients with high-grade ovarian cancer must be tested for germline and/or somatic BRCA1/2 mutations at diagnosis (Level I, Grade A recommendation). 1

Testing for homologous recombination deficiency (HRD) is recommended in advanced high-grade cancers (Level I, Grade A recommendation). 1 These molecular alterations predict the magnitude of benefit from PARP inhibitor therapy 1

Critical Pitfall to Avoid

Adequate tumor tissue must be obtained before neoadjuvant chemotherapy is initiated. 1 If a complete pathological response is achieved following neoadjuvant chemotherapy, sufficient viable tumor tissue may be unavailable for genetic testing after interval cytoreductive surgery 1

Neoadjuvant Chemotherapy Considerations

Neoadjuvant chemotherapy followed by interval cytoreduction may be considered (category 1) for patients with bulky stage III to IV disease who are not surgical candidates 1 However, a gynecologic oncologist must make this assessment before neoadjuvant chemotherapy is administered 1

When disease appears suitable for cytoreduction as assessed by imaging, and there are no surgical or medical contraindications, surgical intervention should be considered first 1

Initial Systemic Treatment

Following surgical staging and cytoreduction, carboplatin in combination with other approved chemotherapeutic agents (typically cyclophosphamide or paclitaxel) is indicated for initial treatment of advanced ovarian carcinoma. 2

The established combination regimen of carboplatin and cyclophosphamide has demonstrated equivalent overall survival compared to cisplatin-based regimens, with a different toxicity profile (more thrombocytopenia and leukopenia, but less nephrotoxicity and neurotoxicity) 2

Pathology Review Requirements

Pathology review at an NCCN Member Institution or by an expert gynecological pathologist is recommended for all patients. 1 High-grade serous carcinoma represents 70% of epithelial ovarian cancer cases and is characterized by near-universal TP53 mutations, BRCA1/2 mutations, and HRD 1

The complexity of subclassification and its effect on personalized treatment choice underline the importance of histological tumor typing by an expert 1