What is the recommended diagnostic workup for suspected ovarian cancer?

Diagnostic Workup for Suspected Ovarian Cancer

The diagnostic workup for suspected ovarian cancer requires transvaginal ultrasound, serum CA-125 measurement, and contrast-enhanced CT of the chest/abdomen/pelvis, followed by pathological examination of tumor tissue obtained via surgery or biopsy. 1

Initial Clinical Assessment

Evaluate for cardinal symptoms that occur more than 12 times per month for less than one year: 2, 3

• Abdominal or pelvic pain
• Increased abdominal size or bloating
• Difficulty eating or early satiety
• Urinary urgency or frequency

Perform abdominal and pelvic examination to detect: 1, 4

• Pelvic masses (noting that pelvic examination has low sensitivity; negative findings should not deter further workup) 2
• Ascites or abdominal distension
• Nodular or fixed masses
• Inguinal, axillary, or supraclavicular lymphadenopathy 1

Laboratory Testing

Serum tumor markers should be obtained based on clinical context: 1

For epithelial ovarian cancer (most common):

• CA-125 is elevated in approximately 85% of advanced disease but only 50% of early-stage (FIGO stage I) cases 1
• CA-125 lacks specificity and can be elevated in benign conditions (endometriosis, pelvic inflammatory disease, ovarian cysts, cirrhosis, heart failure, renal failure) 1, 5

For suspected mucinous carcinoma:

• Measure CEA and CA 19-9 in addition to CA-125 1
• CA-125/CEA ratio ≤25:1 suggests gastrointestinal origin rather than primary ovarian tumor 1, 5
• Consider colonoscopy and gastroscopy if CEA or CA 19-9 are elevated 1

For young patients (<35 years) or suspected germ cell tumors:

• α-fetoprotein (AFP) 1, 4
• β-human chorionic gonadotropin (β-hCG) 1
• Lactate dehydrogenase (LDH) 1

For sex cord-stromal tumors:

• Inhibin is secreted by granulosa cell tumors and serves as a useful marker 1

Additional baseline studies:

• Complete blood count 1
• Liver and renal function tests 1

Imaging Studies

Primary imaging modality:

• Transvaginal and transabdominal ultrasound by an expert examiner is the first-line imaging study 1, 4
• Ultrasound-based diagnostic models (IOTA Simple Rules or IOTA ADNEX) are superior to CA-125 alone for distinguishing benign from malignant tumors 1, 5

Features suggesting malignancy on ultrasound: 1, 4

• Large lesion size (>6 cm warrants referral) 2
• Solid components or papillary projections
• Thick septations (>2-3 mm)
• Irregular internal septations
• Ascites
• Bilateral masses
• Increased vascular flow on Doppler

Advanced imaging for staging and surgical planning:

• Contrast-enhanced CT of chest, abdomen, and pelvis is required for complete clinical staging 1, 4
• MRI may be useful when ultrasound findings are indeterminate or to better characterize malignant features 1
• FDG-PET/CT may be employed for indeterminate lesions after standard imaging 1, 4

Cytological assessment:

• Pleural fluid cytology if pleural effusion is present and safely accessible 1

Pathological Diagnosis

Definitive diagnosis requires pathological examination of adequate tumor tissue: 1

Tissue acquisition:

• Surgical specimen is preferred (obtained during staging laparotomy or laparoscopy) 1
• Avoid fine-needle aspiration in presumed early-stage disease to prevent cyst rupture and peritoneal spillage of malignant cells, which can upstage disease 1, 4
• Image-guided or laparoscopic biopsy may be necessary for patients with bulky disease who are not surgical candidates 1

Pathology requirements:

• Examination by an expert gynecologic pathologist trained in ovarian cancer 1
• Classification according to WHO 2020 criteria 1
• Obtain sufficient tissue for molecular/genetic testing, especially if neoadjuvant chemotherapy is planned (complete pathological response may leave insufficient viable tumor for testing after interval surgery) 1, 4

Special Considerations

For suspected gonadoblastomas in pre-menarche girls:

• Obtain preoperative karyotype due to propensity to arise in dysgenetic gonads 1

For granulosa cell tumors:

• Perform endometrial curettage to rule out concomitant uterine cancer 1

Genetic risk assessment:

• Consider BRCA1/2 testing for patients with family history of breast or ovarian cancer 1, 4
• Consider Lynch syndrome screening (mismatch repair genes) for patients with family history of colorectal cancer, as this confers 10-12% lifetime ovarian cancer risk 5

Critical Pitfalls to Avoid

Do not rely on CA-125 alone for diagnosis: CA-125 has insufficient sensitivity for early disease and lacks specificity 1, 5

Do not perform FNA on presumed early-stage ovarian masses: This risks capsule rupture and peritoneal contamination 1, 4

Do not rely solely on ultrasound for staging: CT of chest/abdomen/pelvis is mandatory for complete staging and surgical planning 1, 4

Do not miss gastrointestinal primaries: In mucinous tumors, measure CEA and CA 19-9, and perform endoscopy if the CA-125/CEA ratio is ≤25:1 1, 5

Do not obtain inadequate tissue: Ensure sufficient tumor sample for molecular testing before initiating neoadjuvant chemotherapy 1, 4

Recognize that negative pelvic examination does not exclude ovarian cancer: Proceed with imaging in symptomatic patients despite normal examination 2