Workup for Suspected Ovarian Cancer
For any patient with suspected ovarian cancer, proceed immediately with transvaginal ultrasound (with color Doppler if available), serum CA-125 measurement, and CT scan of chest/abdomen/pelvis, followed by prompt referral to a gynecologic oncologist if imaging or markers suggest malignancy. 1, 2
Initial Clinical Assessment
History and Physical Examination
- Focus on specific symptoms: abdominal/pelvic pain (most common), bloating, early satiety, urinary frequency, abdominal distension, and unexplained weight changes 2, 3
- Identify high-risk factors: family history of ovarian/breast cancer, BRCA1/BRCA2 mutations (40% and 18% lifetime risk respectively), Lynch syndrome (12% lifetime risk), and advancing age 2, 4
- Perform targeted examination: bimanual pelvic examination for fixed or nodular masses, abdominal examination for ascites, and assessment for pleural effusions in advanced disease 2, 5
Laboratory Testing
Tumor Markers - Standard Panel
- CA-125 is mandatory before surgery and chemotherapy, though it is elevated in only 50% of early-stage disease and 85% of advanced disease 1, 2
- For mucinous or endometrioid tumors: measure CEA and CA 19-9 if CA-125 is not elevated, as a CA-125/CEA ratio ≤25:1 suggests gastrointestinal origin rather than primary ovarian cancer 1, 6, 2
- For young women (<35 years): measure alpha-fetoprotein (AFP) and beta-HCG to exclude germ cell tumors 1, 2
Critical Pitfall
Never rely on CA-125 alone for diagnosis—it can be falsely elevated in benign conditions (endometriosis, pelvic inflammatory disease, cirrhosis with ascites) and non-gynecological malignancies (colorectal, breast cancer) 6, 2
Imaging Studies
Primary Imaging
- Transvaginal ultrasound with color/power Doppler is the first-line imaging modality to evaluate ovarian masses 1, 2
- Look for malignant features: solid components, papillary projections, thick septations, ascites, or complex masses 6
- Use structured risk assessment: O-RADS classification (O-RADS 5 indicates ≥50% malignancy risk) 6
Staging and Surgical Planning
- CT scan of chest, abdomen, and pelvis with contrast is mandatory for complete clinical staging, assessment of metastases, and surgical planning 1, 2
- Chest imaging is necessary despite lack of direct evidence, as it evaluates for pleural effusions and thoracic extension 1
Advanced Imaging (When Indicated)
Additional Diagnostic Considerations
For Suspected Mucinous Carcinoma
- Measure CEA and CA 19-9 in addition to CA-125 to distinguish primary ovarian tumors from gastrointestinal metastases 6, 2
- Consider gastrointestinal evaluation (endoscopy/colonoscopy) if CEA or CA 19-9 are elevated, especially if CA-125/CEA ratio is <25:1 6, 7
Tissue Diagnosis Considerations
- Avoid fine-needle aspiration in presumed early-stage disease to prevent rupturing the cyst and spilling malignant cells into the peritoneal cavity 1, 7
- FNA may be necessary only in patients with bulky disease who are not surgical candidates 1
- Surgical exploration with intraoperative frozen section is the standard approach for definitive diagnosis and staging 1, 7
Referral Criteria
Immediate Gynecologic Oncology Referral Required For:
- Postmenopausal women with elevated CA-125 6
- Any patient with nodular or fixed pelvic mass, ascites, or evidence of metastatic disease 6
- Suspicious ultrasound findings suggesting malignancy (O-RADS 4-5) 6
- Family history of breast or ovarian cancer with elevated markers or suspicious imaging 6
Pathological Requirements
Tissue Handling and Analysis
- Adequate tissue sampling is critical: peritoneal biopsies alone are insufficient and do not prove ovarian origin or degree of malignancy 1, 7
- Transport intact, unopened tissue rapidly to the laboratory with appropriate fixative 1
- Comprehensive pathological examination must include weight, measurements, detailed macroscopic description, and multiple well-directed samples (one per centimeter along greatest diameter) 1
- Routine freezing of representative samples is recommended 1
Intraoperative Assessment
- Frozen section examination can guide surgical extent but has limitations in distinguishing well-differentiated adenocarcinomas from borderline tumors 1, 7
Common Pitfalls to Avoid
- Do not delay surgery for percutaneous biopsy—this risks tumor spillage and upstaging in early disease 7
- Do not perform inadequate imaging—relying solely on ultrasound without CT for complete staging is insufficient 2
- Do not obtain insufficient tissue—inadequate tumor samples compromise pathological examination, especially if neoadjuvant chemotherapy is planned 2
- Do not miss gastrointestinal primary—always rule out metastatic disease in mucinous tumors 2, 7