What is the recommended evaluation and management for suspected ovarian cancer?

Evaluation and Management of Suspected Ovarian Cancer

All women with suspected advanced ovarian cancer (stage IIIC or IV) must be evaluated by a gynecologic oncologist prior to initiating any therapy. 1

Initial Clinical Evaluation

Mandatory Imaging Studies

• CT scan of abdomen and pelvis with oral and IV contrast is required to evaluate disease extent and surgical resectability 1
• Chest imaging with CT is preferred over plain radiography to assess for thoracic metastases 1
• Additional imaging tools may refine assessment, including laparoscopic evaluation, FDG-PET scan, or diffusion-weighted MRI 1

Laboratory Assessment

• Serum CA-125 measurement should be obtained, though it has limited sensitivity (only 50% in stage I disease) but high specificity (98.5% in women >50 years when elevated) 1, 2
• CA-125/CEA ratio >25 favors ovarian origin over gastrointestinal primary 1
• Additional tumor markers (CA 19-9, CEA) help distinguish primary ovarian from metastatic gastrointestinal tumors 1

Pathologic Confirmation

• Tissue diagnosis is mandatory before initiating neoadjuvant chemotherapy - either through biopsy or cytology from ascites/pleural effusion 1
• If biopsy is not feasible, cytopathology combined with CA-125:CEA ratio ≥25 can be used 1
• Laparoscopic evaluation should be considered for more accurate assessment of resectability 1

Treatment Decision Algorithm

Primary Cytoreductive Surgery (PCS) - Preferred When:

Primary cytoreductive surgery is preferred if there is high likelihood of achieving cytoreduction to <1 cm residual disease (ideally no visible disease) with acceptable morbidity 1

Factors predicting optimal cytoreduction include: 1

• Age <60 years
• CA-125 <500 U/mL
• ASA Physical Status classification 1-2
• Absence of specific CT findings (see below)

Neoadjuvant Chemotherapy (NACT) - Indicated When:

Women with high perioperative risk or low likelihood of optimal cytoreduction should receive neoadjuvant chemotherapy 1

CT findings predicting suboptimal cytoreduction (favoring NACT): 1

• Retroperitoneal lymph nodes above renal hilum >1 cm
• Diffuse small bowel adhesions or thickening
• Small bowel mesentery lesions >1 cm
• Root of superior mesenteric artery lesions >1 cm
• Perisplenic lesions >1 cm
• Lesser sac lesions >1 cm

Clinical factors favoring NACT: 1

• High perioperative risk (ASA class 3-4)
• Stage IV disease with larger metastatic tumors (>45 mm)
• Poor performance status

Evidence Supporting Both Approaches

• NACT is noninferior to PCS regarding overall and progression-free survival in randomized trials 1
• NACT results in lower perioperative morbidity and mortality compared to PCS 1
• Secondary analysis suggests stage IIIC with smaller tumors (≤45 mm) may benefit more from PCS, while stage IV with larger tumors (>45 mm) may benefit more from NACT 1

Surgical Principles for Early-Stage Disease

For Disease Apparently Confined to Ovary/Pelvis:

Comprehensive surgical staging must include: 1

• Peritoneal cytology (ascites aspiration or lavage)
• Visualization and selective biopsy of all peritoneal surfaces
• Random peritoneal biopsies (pelvis, paracolic gutters, diaphragm) if no suspicious areas
• Total hysterectomy, bilateral salpingo-oophorectomy
• Omentectomy
• Aortic lymph node dissection (to level of renal vessels preferred)
• Pelvic lymph node dissection

Fertility-sparing unilateral salpingo-oophorectomy may be considered in select patients desiring fertility preservation 1

For Advanced Disease (Upper Abdomen Involvement):

Goal is maximal cytoreduction with residual disease <1 cm, ideally no visible disease 1

Chemotherapy Regimens

First-Line Treatment for Advanced Disease:

For previously untreated ovarian carcinoma, two regimens are FDA-approved: 3

1. Paclitaxel 175 mg/m² IV over 3 hours followed by cisplatin 75 mg/m² every 3 weeks 3
2. Paclitaxel 135 mg/m² IV over 24 hours followed by cisplatin 75 mg/m² every 3 weeks 3

Alternative platinum-based regimen: 4

• Carboplatin 300 mg/m² IV plus cyclophosphamide 600 mg/m² IV every 4 weeks for 6 cycles 4

Maintenance Therapy:

Most patients with advanced-stage disease receive maintenance therapy with bevacizumab and/or PARP inhibitors 5

• Individuals with BRCA-related variants have approximately 70% 5-year survival with PARP inhibitor treatment 5

Critical Pitfalls to Avoid

Referral Patterns:

• Only 39% of family physicians and 51% of general internists self-report gynecologic oncologist referral for suspicious masses, contributing to high rates of noncomprehensive surgery 6
• One-third of ob-gyns indicate they would perform surgery themselves rather than refer 6
• This represents a major quality gap, as gynecologic oncologist involvement improves outcomes 1, 6

Staging Errors:

• Up to 40% of patients may be understaged at laparotomy when comprehensive staging is not performed 1
• Incomplete staging leads to missed malignancy in approximately 30% of cases 7

Treatment Delays:

• Treatment should not be delayed for genetic counseling referral, as delay is associated with poorer outcomes 1
• However, all patients should undergo genetic risk evaluation and BRCA1/2 testing to inform maintenance therapy options 1

Dosing Considerations:

• Courses should not be repeated until neutrophils ≥1,500 cells/mm³ and platelets ≥100,000 cells/mm³ for solid tumors 3
• Renal function must be assessed before carboplatin dosing, with dose adjustments for creatinine clearance <60 mL/min 4
• All patients require premedication (dexamethasone, diphenhydramine, H2-blocker) to prevent severe hypersensitivity reactions 3

Prognosis

• Early-stage disease (I-II) has 70-95% 5-year survival with appropriate treatment 5
• Advanced-stage disease (III-IV) has 10-40% 5-year survival overall 5
• Approximately 75% of advanced-stage patients relapse within 2 years despite initial 80% remission rate 5