Ultrasound is typically the first-line imaging modality for evaluating adnexal masses and can effectively triage the majority of adnexal masses into benign or malignant categories. It is the most commonly used initial imaging study [25,26].

A/P CT is recommended for preoperative staging assessment, estimation of resectability, and surgical planning. It is generally more useful than ultrasound for assessing abdominal metastases [28,31]. CT should be performed with oral and iodinated IV contrast (unless contraindicated due to anaphylaxis or significant renal dysfunction) with or without rectal contrast.

MRI has been shown to provide equivalent accuracy for staging and comparable accuracy for predicting peritoneal tumor volume compared with CT. It can be useful if CT results are inconclusive and is preferred in select patients with renal dysfunction over CT [27,28]. MRI is performed with gadolinium-based contrast agents (unless contraindicated due to anaphylaxis).

FDG-PET/CT for assessing advanced disease may be useful if CT results are indeterminate and may be able to detect distant metastases [32,33]. The Panel recommends PET/CT, MRI, or PET/MRI for indeterminate lesions if the results of the scan will alter management. PET/CT is performed from skull base to mid-thigh.

Although there is no direct evidence that chest CT is necessary, the Panel recommends it as part of the overall evaluation of a patient if clinically indicated. Chest CT can detect metastatic or disseminated disease, which may help with treatment planning.

Intraoperative pathologic evaluation with frozen sections may assist in surgical management decisions, particularly for determining whether fertility-sparing surgery is appropriate and for guiding the extent of surgical staging.

When biopsy is not feasible, cytopathology from ascites or pleural effusion combined with a CA-125:CEA ratio of >25 can be used to support the diagnosis of ovarian cancer.

FNA should be avoided for diagnosis of ovarian cancer in patients with presumed early-stage disease to prevent rupturing the cyst and spilling malignant cells into the peritoneal cavity. However, FNA may be necessary in patients with bulky disease who are not candidates for primary debulking [2,3].

GI tract evaluation is especially important in those with elevated serum CEA and an adnexal mass to distinguish between a GI primary tumor that has metastasized to the ovary and primary mucinous carcinoma of the ovary. Upper and lower GI tract should be carefully evaluated for mucinous histology [50].

Refer patients who wish to retain fertility to a reproductive endocrinologist for consultation, including possibility of oocyte collection before chemotherapy is initiated.

Baseline CBC is essential to assess for anemia, thrombocytopenia, or leukopenia that may affect treatment planning and to establish baseline values for monitoring during chemotherapy.

Assessment of renal and hepatic function is required to determine eligibility for platinum-based chemotherapy and to monitor for treatment-related toxicities.

Serum CA-125 levels tend to correlate with the clinical course of disease, especially in those with elevated pretreatment levels. CA-125 can be useful in treatment planning, monitoring response to therapy, and surveillance for recurrence [34,35]. The CA-125:CEA ratio of >25 (combined with cytopathology from ascites or pleural effusion) may be suspicious for ovarian cancer when biopsy is not feasible.

Additional tumor markers may include inhibin, beta-human chorionic gonadotropin (β-hCG), alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), CA 19-9, and HE4 [38–42]. HE4 may be a useful prognostic marker and may improve early detection of recurrence relative to CA-125 alone [35–37].

Comprehensive cross-sectional imaging from chest to pelvis is used for staging assessment. C/A/P CT is the standard imaging modality for staging and follow-up of epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer [OV-A].

Chest CT and A/P MRI may be used as an alternative to C/A/P CT for staging assessment, particularly when CT is inconclusive or when MRI provides superior soft tissue characterization [OV-A].

PET imaging may be useful for detection of recurrent disease, evaluation of indeterminate lesions, and assessment of disease extent. PET/CT or PET/MRI is recommended for patients with recurrent disease [OV-A].

In select patients with advanced-stage disease, laparoscopy may be useful to evaluate whether optimal cytoreduction can be achieved by primary debulking surgery or whether neoadjuvant chemotherapy may be a better initial treatment option [72–75]. A randomized trial showed that only 10% of patients randomized to assessment laparoscopy had >1 cm residual disease after surgery compared to 39% who underwent primary cytoreductive surgery [73].

Germline and somatic BRCA1/2 pathogenic/likely pathogenic (P/LP) variants inform maintenance therapy selection with PARP inhibitors. All patients with suspected ovarian cancer should have genetic risk evaluation and germline and somatic BRCA1/2 testing if not previously done [c,d,e,h].

In the absence of a BRCA1/2 mutation, HRD status may provide information on the magnitude of benefit of PARP inhibitor (PARPi) therapy. Current clinical HRD tests are proxy measures of HRD and lack accuracy in fully predicting functional HRD. HRD testing is recommended for those patients without germline BRCA1/2 P/LP variants [OV-C].

Validated biomarker testing should be performed in a CLIA-approved facility using the most recent available tumor tissue. Tumor biomarker analysis is recommended to include tests to identify potential benefit from targeted therapeutics that have tumor-specific or tumor-agnostic benefit including, but not limited to: HER2 status (by IHC), PD-L1 (IHC, CPS), BRCA1/2, HRD status, microsatellite instability (MSI), mismatch repair (MMR), tumor mutational burden (TMB), BRAF, KRAS, FRα (FOLR1), RET, and NTRK1/2/3 [OV-C, OV-6, OV-7, OV-8].

PD-L1 combined positive score (CPS) testing is relevant for selection of immunotherapy, specifically pembrolizumab. Tumors with a CPS ≥1 determined by an FDA-approved test are considered PD-L1 positive [footnote bb].

MSI-H and dMMR tumors may respond to checkpoint inhibitor therapy (dostarlimab-gxly, pembrolizumab) with tumor-agnostic FDA approval [42,43].

FRα expression is relevant for selection of mirvetuximab soravtansine-gynx, an antibody-drug conjugate with activity in platinum-resistant ovarian cancer [35,36,53,54,274,277].

TMB-H (≥10 mutations/megabase) may identify patients who could benefit from pembrolizumab based on tumor-agnostic indication [43].

Germline SMARCA4 testing should be performed after surgery if not previously done in patients with small cell carcinoma of the ovary hypercalcemic type. If germline SMARCA4 negative, fertility-sparing surgery can be considered after appropriate counseling, though there are limited data on the safety and feasibility of this approach.

MSI/MMR testing is recommended for all patients with endometrioid carcinoma, as it may identify patients who could benefit from immunotherapy and has implications for Lynch syndrome screening.