What is the recommended workup for a complex ovarian cyst, including history, pelvic exam, imaging, serum CA‑125 testing, and criteria for referral or surgery?

Workup for Complex Ovarian Cyst

For a complex ovarian cyst, obtain transvaginal ultrasound with color Doppler as first-line imaging, measure serum CA-125 (plus CEA and CA 19-9 if mucinous features suspected), perform CT chest/abdomen/pelvis for complete staging, and refer postmenopausal women or those with concerning features to a gynecologic oncologist for surgical evaluation. 1, 2

Initial Clinical Assessment

History and Symptom Evaluation

• Focus on red-flag symptoms: persistent abdominal/pelvic pain, bloating, early satiety, urinary urgency/frequency, unexplained weight loss, or abdominal distension—these suggest possible malignancy, particularly in women over 50 2, 3
• Assess risk factors: family history of ovarian/breast cancer, BRCA1/2 mutations, Lynch syndrome, or personal history of endometriosis 2
• Document menopausal status: postmenopausal women have significantly higher malignancy risk (3:1,000 vs 1:1,000 in premenopausal women) 3

Physical Examination

• Perform abdominal/pelvic examination to detect pelvic masses, nodularity, fixation, or ascites 1, 2
• Assess for metastatic disease signs: pleural effusions, lymphadenopathy, or hepatomegaly 2

Imaging Protocol

Primary Imaging

• Transvaginal ultrasound with color or power Doppler is the first-line imaging modality 1, 2
• Concerning ultrasound features include: solid components, papillary projections, thick septations (>2-3mm), ascites, bilateral masses, or irregular borders 1, 2
• Use O-RADS classification for risk stratification: O-RADS 2 (<1% malignancy), O-RADS 3 (1-10%), O-RADS 4 (10-50%), O-RADS 5 (≥50%) 4

Advanced Imaging

• CT chest/abdomen/pelvis with contrast is mandatory for complete staging and surgical planning in suspected malignancy 1, 2, 5
• MRI may be useful when ultrasound is indeterminate or unreliable for determining malignant potential 1
• FDG-PET/CT can be considered for indeterminate lesions when standard imaging is inconclusive 1, 5

Laboratory Testing

Tumor Marker Strategy

• Measure CA-125 in all patients with complex cysts, recognizing it is elevated in only 50% of early-stage ovarian cancers but 85% of advanced disease 4, 2
• Add CEA and CA 19-9 if mucinous features are present on imaging; a CA-125/CEA ratio ≤25:1 suggests gastrointestinal origin rather than primary ovarian cancer 4, 2, 5
• In women <35 years, measure AFP and β-hCG to exclude germ cell tumors 1, 5

CA-125 Interpretation Caveats

• CA-125 is NOT specific for ovarian cancer—it can be elevated in endometriosis, pelvic inflammatory disease, cirrhosis, heart failure, and renal failure 4
• Never use CA-125 alone to make surgical decisions; it must be interpreted alongside imaging and clinical findings 4
• In postmenopausal women with complex cysts >5cm, CA-125 may provide added value for malignancy suspicion 6
• In premenopausal women, CA-125 has limited added value due to high false-positive rates from benign conditions 6

Referral Criteria to Gynecologic Oncologist

Absolute Indications for Referral

• Postmenopausal women with elevated CA-125, regardless of cyst characteristics 4, 2
• Any patient with nodular or fixed pelvic mass, ascites, or evidence of metastatic disease 2
• Complex cysts in postmenopausal women of any size carry significant malignancy risk and warrant surgical evaluation 6
• Premenopausal women with complex cysts >5cm and elevated CA-125 3
• Family history of breast or ovarian cancer (BRCA mutations) 2

Conservative Management Criteria

• Simple unilocular cysts <5cm in premenopausal women can be followed with serial ultrasound, as these are typically functional and resolve spontaneously 6, 3, 7
• Simple cysts in postmenopausal women can be safely followed without intervention per ACOG guidelines, even if >5cm, provided CA-125 is normal (<35 IU/mL) 8, 7
• Follow-up protocol: annual transvaginal ultrasound for 3 years and annual CA-125 for 5 years in low-risk postmenopausal women 7

Critical Pitfalls to Avoid

• Avoid fine-needle aspiration in presumed early-stage disease, as this risks cyst rupture and peritoneal spillage of malignant cells 1, 5
• Do not delay surgery for tissue diagnosis in suspicious cases—percutaneous biopsy risks tumor spillage and upstaging 5
• Do not rely on CA-125 alone—normal values occur in 50% of early-stage cancers 4, 5
• For mucinous tumors, always rule out gastrointestinal primary with endoscopy/colonoscopy if CEA or CA 19-9 are elevated 2, 5
• Ensure adequate surgical expertise—refer suspected malignancies to gynecologic oncologists for proper comprehensive staging 2, 5