Ovarian Cancer Diagnostics

Laboratory Tests and Ancillaries

Laboratory tests are recommended in women >40 years of age with persistent unexplained gynecologic or gastrointestinal symptoms. Complete blood count (CBC), blood chemistry with liver function tests (LFTs), and total serum protein should be requested, and an evaluation of nutritional status should also be assessed.  

Serum CA-125 levels are increased in 85% of women with advanced ovarian cancer and in about 50% of women with stage 1 disease. If the results showed levels of ≥35 IU/mL, an ultrasound exam of the abdomen and pelvis should be performed. Unreliable in differentiating benign from malignant masses in premenopausal women because of an increased rate of false positives or reduced specificity. False positive results may be secondary to peritoneal inflammation in endometriosis or adenomyosis, pelvic inflammatory disease, menstruation, uterine fibroids, or benign cysts.  

Studies show that human epididymis protein 4 (HE4) has a higher positive predictive value as a tumor marker than CA-125. It has a higher sensitivity during the early stages of ovarian cancer. The combination of HE4 and CA-125 in the risk of malignancy algorithms has good sensitivity and specificity in ovarian cancer triage both in premenopausal and postmenopausal women.  

Alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH) are markers for malignant germ cell tumors and may be used to help in intraoperative diagnosis, preoperative planning, and post-treatment monitoring for recurrence. They should be measured in all women <40 years of age with a complex ovarian mass because of the possibility of germ cell tumors. They are primarily used to evaluate adnexal masses found during adolescence or young adulthood.  

Carcinoembryonic antigen (CEA) and inhibin are measured to assess for less common ovarian histopathologies if clinically indicated.  

Homologous recombination deficiency (HRD) testing may also be done; positive results occur in patients with germline BRCA1 and BRCA2 (wild type or unknown) mutations. This may provide information on the magnitude of the benefit of poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitor therapy.  

Histopathology  

The diagnosis of ovarian carcinoma can only be made on the basis of histological examination. Invasive growth is a prerequisite for the diagnosis of ovarian carcinoma. Around 85-95% of cases are from epithelial cells which are commonly diagnosed in women >50 years old. Around 5-8% of cases are from sex cord embryonic gonads which may occur in women of any age. Certain tumors such as androblastomas may be more common in adolescence. Around 3-5% of cases are from germ cells which usually occur in patients 15-19 years of age.  

Other Tests  

Laparoscopy provides a view of the organs that can help plan surgery or other treatments and can help confirm the stage of the cancer. Laparoscopic biopsy should be considered if percutaneous image-guided biopsy is not feasible or has not produced an adequate sample. Exploratory laparotomy allows adequate exposure and careful examination of the abdominal cavity for surgical staging. 

Imaging

Imaging is used to confirm the presence of a pelvic mass and to expeditiously distinguish benign adnexal lesions from those requiring further pathological evaluation for malignancy. No objective imaging criteria are available to predict surgical resectability but may be used to gain preoperative information regarding the extent of the disease at the start of treatment. Imaging done is with contrast except if contraindicated.  

Ultrasound is the single most effective way of evaluating an ovarian mass. Transvaginal ultrasonography is preferred due to its increased sensitivity over transabdominal ultrasound, but both may be used in assessing larger masses and extra-ovarian disease. No single ultrasound finding differentiates benign from malignant ovarian masses. Features such as complexity with solid and cystic areas, extramural fluid, echogenicity, wall thickening, septum thickness of >3 mm without sharp boundary line, papillary masses in the cyst cavity, and ascites are suggestive of cancer.  

Computed tomography (CT) scan of the pelvis and abdomen should be done to establish the extent of the disease if ultrasound and serum CA-125 results, and clinical status of the patient suggests ovarian cancer. It is also done in the case of an abdominal or pelvic mass of unknown origin. It is useful in the diagnosis and planning of management for advanced cancer and is also helpful in detecting the presence of pleural fluid and metastases to other parts of the body (ie lungs, mediastinal lymph nodes, omentum, liver, spleen, or retroperitoneum).  

Other imaging studies may also be helpful. Chest X-ray may be used to detect lung metastases. A positron emission tomography (PET) scan is helpful to spot small collections of cancer cells but is not recommended for primary cancer detection because of high false positive rates. The primary role of PET scans is to help the selection of patients for secondary debulking surgery by excluding additional sites of disease not seen on CT scans and not amenable to cytoreduction. Magnetic resonance imaging (MRI) is not used routinely for assessing women with suspected ovarian cancer. Colonoscopy may be done if there is a suspicion of or to rule out bowel involvement.