Introduction: Who Should Undergo Diagnostics

Ovarian epithelial cancer is the most common form of ovarian cancer, accounting for about 90% of all ovarian cancer cases. This type of cancer develops in the thin layer of tissue covering the outside of the ovaries, but it can also begin in the lining of the fallopian tubes or in the peritoneum, which is the tissue that lines the abdominal cavity.^[1] Because these cancers grow in similar ways and behave alike, doctors often group them together and treat them using the same approaches.^[3]

One of the biggest challenges with epithelial ovarian cancer is that it rarely causes noticeable symptoms in its early stages. Most people don’t realize anything is wrong until the cancer has already spread beyond the ovaries. In fact, nearly 70% of high-grade serous ovarian cancer cases—the most common and aggressive subtype—are diagnosed at stage 3 or 4, meaning the cancer has already reached nearby organs or lymph nodes.^[1] This late detection is a major reason why ovarian cancer has such high mortality rates compared to other gynecologic cancers.^[2]

Women over the age of 65 who have gone through menopause are at the highest risk for developing ovarian epithelial cancer. More than half of all diagnoses occur in this age group.^[17] However, younger women can also develop the disease, particularly if they have certain risk factors. Anyone with a family history of ovarian cancer, especially in a mother, sister, or daughter, faces an increased risk.^[3] People who carry inherited mutations in genes called BRCA1 and BRCA2 are at significantly higher risk, with lifetime ovarian cancer risks ranging from 17% to 40% depending on which gene is affected.^[7]

Women who have had breast cancer or colon cancer also face a higher likelihood of developing ovarian cancer. Other risk factors include having endometriosis, taking hormone therapy after menopause, being obese, and being taller than average.^[7] Women with these risk factors should discuss their concerns with their gynecologist and consider more frequent check-ups.

It’s advisable to seek medical evaluation if you experience symptoms that persist and don’t go away on their own. As the cancer progresses and spreads into the peritoneum, fluid often accumulates in the abdomen, leading to noticeable changes. Common symptoms include abdominal pain, bloating, swelling in the abdomen, difficulty eating or feeling full quickly, nausea and vomiting, and pelvic pain.^[1] Less common warning signs include changes in bowel habits, a strong urge to urinate or urinating more frequently than usual, and vaginal bleeding.^[17]

Many of these symptoms are vague and can easily be mistaken for digestive problems like gas, constipation, or bloating.^[16] This is why ovarian cancer is sometimes called a “silent” disease—it doesn’t announce itself loudly. However, if these symptoms are new for you, happen frequently, and don’t improve after a few weeks, it’s important to see your doctor. Early consultation can make a significant difference, even though the symptoms themselves are not specific to ovarian cancer.

Women who know they have a family history of ovarian or breast cancer, or who have tested positive for BRCA gene mutations, may want to discuss preventive strategies with their healthcare provider. Some women at very high risk choose to undergo surgery to remove their ovaries and fallopian tubes as a way to reduce their cancer risk, though this is a major decision that requires careful consideration.^[3]

Diagnostic Methods

When ovarian epithelial cancer is suspected, doctors use a combination of physical examinations, imaging tests, blood tests, and tissue analysis to confirm the diagnosis and understand how far the cancer has spread. No single test can definitively diagnose ovarian cancer on its own, so doctors rely on multiple approaches to build a complete picture.

Physical Examination

The diagnostic process typically begins with a thorough physical examination and a review of the patient’s medical history. The doctor will ask about symptoms, risk factors, and family history of cancer. A pelvic exam is a key part of this initial assessment. During a pelvic exam, the doctor feels the ovaries and surrounding organs to check for abnormal areas, lumps, or signs of disease.^[6] While a pelvic exam can detect some abnormalities, it cannot definitively diagnose cancer. Ovarian tumors, especially in early stages, may not be large enough to feel during a physical exam.

Imaging Tests

Imaging tests are essential for seeing inside the body and identifying any suspicious masses or growths. Several types of imaging may be used:

• Ultrasound and transvaginal ultrasound are often the first imaging tests ordered. An ultrasound uses sound waves to create pictures of the ovaries and surrounding structures. A transvaginal ultrasound involves inserting a small probe into the vagina to get a closer, clearer view of the ovaries. These tests can help determine the size and shape of any masses and whether they appear solid or filled with fluid.^[6]
• CT scans (computed tomography scans) use X-rays and computer technology to create detailed cross-sectional images of the abdomen and pelvis. CT scans can show whether cancer has spread to other organs, lymph nodes, or tissues.^[6]
• MRI scans (magnetic resonance imaging) use magnets and radio waves to produce detailed images of soft tissues. MRI may be used when doctors need more detailed information about a mass or when CT images are unclear.^[6]
• PET scans (positron emission tomography) can help detect cancer that has spread to distant parts of the body. PET scans involve injecting a small amount of radioactive sugar into the bloodstream, which cancer cells absorb more readily than normal cells, making them visible on the scan.^[6]
• Chest X-rays may be performed to check whether cancer has spread to the lungs.^[6]

Imaging tests help doctors see where tumors are located and how large they are, but they cannot confirm that a mass is cancerous. For that, doctors need to examine cells or tissue under a microscope.

Blood Tests

A blood test called the CA-125 assay is commonly used when ovarian cancer is suspected. CA-125 is a protein that is often elevated in the blood of women with ovarian cancer.^[6] However, this test is not perfect. CA-125 levels can be elevated for reasons other than cancer, such as endometriosis, pelvic inflammatory disease, or even menstruation. Additionally, not all women with ovarian cancer have elevated CA-125 levels, especially in early stages. Therefore, the CA-125 test is usually used in combination with other tests rather than on its own.

Other blood tests may be performed to assess overall health and organ function, particularly if surgery or chemotherapy is being considered.

Biopsy and Tissue Diagnosis

The only way to definitively diagnose ovarian cancer is through a biopsy, which involves removing a sample of cells or tissue from the affected area and examining it under a microscope. In many cases, the biopsy is performed during surgery to remove the tumor.^[6] Surgeons may remove the entire ovary or a portion of the suspicious tissue, which is then sent to a pathologist for analysis.

Pathologists examine the cells to determine whether they are cancerous and, if so, what type of epithelial ovarian cancer is present. There are several subtypes of epithelial ovarian cancer, including high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma.^[1] Each subtype has different characteristics, growth patterns, and responses to treatment, so accurate identification is crucial.

The pathologist also assigns a grade to the cancer, which describes how abnormal the cells look under the microscope. Grade 1 cells look similar to normal tissue and tend to grow slowly. Grade 3 cells look very different from normal tissue and are more aggressive.^[7]

Staging

Once ovarian cancer is diagnosed, doctors need to determine the stage of the disease—that is, how far it has spread. Staging helps guide treatment decisions and provides information about prognosis. Ovarian cancer is staged from 1 to 4:

• Stage 1: Cancer is confined to one or both ovaries.
• Stage 2: Cancer has spread to nearby pelvic structures, such as the uterus or fallopian tubes.
• Stage 3: Cancer has spread to the lining of the abdomen (peritoneum) or to lymph nodes.
• Stage 4: Cancer has spread to distant organs, such as the lungs or liver.

Staging is typically completed during surgery, when doctors can directly see the extent of cancer spread and take tissue samples from different areas of the abdomen. Imaging tests and blood tests also contribute to staging information.^[2]

Genetic Testing

Because up to 20% of ovarian cancers are linked to inherited gene mutations, doctors often recommend genetic testing for women diagnosed with ovarian cancer.^[8] This testing looks for mutations in genes like BRCA1, BRCA2, and others associated with hereditary cancer syndromes. Knowing whether a patient carries these mutations can influence treatment decisions, particularly regarding newer targeted therapies. It also provides important information for family members, who may want to undergo genetic counseling and testing themselves.

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments, diagnostic methods, or preventive strategies. Many women with ovarian epithelial cancer choose to participate in clinical trials to access cutting-edge therapies that are not yet widely available. However, not everyone is eligible for every clinical trial. Trials have specific entry criteria, and diagnostic tests are used to determine whether a patient meets these requirements.

Standard Diagnostic Criteria

Clinical trials typically require participants to have a confirmed diagnosis of ovarian epithelial cancer, often verified through biopsy and pathology reports. The trial protocol may specify the stage, grade, or subtype of cancer that is eligible. For example, a trial testing a new treatment for high-grade serous ovarian cancer may exclude patients with low-grade serous or clear cell carcinomas.

Imaging tests such as CT scans, MRI scans, or PET scans are often required to assess the extent of disease before enrollment. These scans provide baseline measurements of tumor size and location, which can be compared to later scans to determine whether the treatment is working.^[15]

Blood Tests and Biomarkers

Many clinical trials require blood tests to measure specific biomarkers or assess overall health. The CA-125 blood test, for example, may be used as a baseline measurement and monitored throughout the trial to track treatment response. Some trials also test for genetic mutations like BRCA1 or BRCA2, as certain treatments work better in patients with these mutations.^[16]

Trials testing new targeted therapies often require testing for specific proteins or receptors on cancer cells. For instance, a trial involving a drug that targets the folate receptor alpha protein would require patients to have tumors with high levels of this protein.^[12]

Performance Status and Organ Function

Clinical trials also assess whether patients are healthy enough to tolerate the experimental treatment. Doctors evaluate what’s called performance status, which is a measure of how well a person can perform daily activities. Patients who are very weak or ill may not be eligible for certain trials.

Blood tests are used to check the function of vital organs, including the kidneys, liver, and bone marrow. This is important because many cancer treatments can affect these organs, and trials need to ensure that participants can safely receive the treatment being tested.^[2]

Imaging and Response Assessment

Throughout a clinical trial, participants undergo regular imaging tests to monitor how the cancer is responding to treatment. These tests are compared to the baseline images taken before the trial began. Doctors look for changes in tumor size, new growths, or signs that the cancer is spreading. This information helps researchers understand whether the treatment is effective.

Participation in a clinical trial can provide access to promising new therapies and contribute to advancing knowledge about ovarian cancer treatment. Women interested in clinical trials should discuss the option with their oncologist and ask about available studies for which they might be eligible.