Introduction: Who Should Consider Diagnostic Testing

Endometrial cancer is a condition where cells in the lining of the uterus, called the endometrium, begin to grow out of control. This cancer most commonly affects women after they have gone through menopause, though it can occur at other times as well. Knowing when to seek medical attention and undergo testing can make a significant difference in catching the disease early.^[1]

Anyone who notices unusual symptoms should consider talking to their doctor about diagnostic testing. The most common warning sign is abnormal vaginal bleeding. For women who have already experienced menopause, this means any bleeding or spotting at all, even just a small amount. Before or during menopause, symptoms can include irregular menstrual bleeding, spotting between periods, or bleeding that is extremely heavy or lasts much longer than usual. Other signs that may suggest a problem include pelvic pain or cramping in the lower belly, difficulty or pain during urination, pain during sexual activity, or unusual vaginal discharge in women who have already gone through menopause.^[2][5]

It is important to understand that these symptoms do not automatically mean you have endometrial cancer. Many other conditions affecting the reproductive organs can cause similar issues. However, because early detection greatly improves the chances of successful treatment, it is always advisable to see a healthcare provider if you notice any of these changes. Getting an accurate diagnosis helps ensure you receive the right treatment if needed.^[5]

Certain groups of women are at higher risk and may benefit from earlier or more frequent screening discussions with their doctors. Risk factors include being overweight or obese, having metabolic syndrome or type 2 diabetes, never having given birth, starting menstruation at an early age, entering menopause later than average, having polycystic ovary syndrome, taking estrogen-only hormone replacement therapy after menopause, taking tamoxifen to treat or prevent breast cancer, having a family history of endometrial cancer in a close relative such as a mother or sister, and having certain genetic conditions like Lynch syndrome. Women with a condition called endometrial hyperplasia, where the lining of the uterus becomes too thick and shows changes that can lead to cancer, should also have regular monitoring.^[2][6]

Classic Diagnostic Methods for Endometrial Cancer

When you visit your doctor with symptoms that could suggest endometrial cancer, they will begin with a careful evaluation to understand what might be causing your symptoms. This process typically starts with a detailed discussion of your medical history, including your menstrual patterns, risk factors, and any symptoms you have been experiencing. The doctor will then perform a physical examination.^[10]

Pelvic Examination

A pelvic exam is often one of the first steps in evaluating possible endometrial cancer. During this examination, the doctor carefully inspects the outer parts of the reproductive organs. They insert a device called a speculum into the vagina, which gently opens the vaginal canal so the doctor can look for any visible signs of cancer or other problems. The doctor also inserts two fingers of one hand into the vagina while pressing on the abdomen with the other hand. This allows them to feel the size and shape of the uterus and ovaries and check for any unusual masses or areas of tenderness.^[10]

While a pelvic exam is important, it cannot definitively diagnose endometrial cancer on its own. The exam helps the doctor decide whether further testing is necessary and what types of tests would be most helpful.^[10]

Transvaginal Ultrasound

A transvaginal ultrasound is an imaging test that uses sound waves to create pictures of the inside of the reproductive organs. During this procedure, a healthcare professional or technician inserts a wand-like device called a transducer into the vagina while you lie on your back on an examination table. The transducer sends out sound waves that bounce off internal structures and create images that appear on a screen. These images show the uterus, ovaries, and other pelvic organs.^[10]

This test is especially useful because it can show the thickness of the endometrium. If the lining appears thicker than normal, it may suggest the presence of cancer or precancerous changes. The ultrasound also helps doctors see if there are any masses or other abnormalities in the uterus or nearby organs. The procedure is generally not painful, though some women may feel mild discomfort. Importantly, a transvaginal ultrasound does not expose you to radiation, unlike X-rays or CT scans.^[10]

Endometrial Biopsy

An endometrial biopsy is the most definitive way to diagnose endometrial cancer. During this procedure, a doctor removes a small sample of tissue from the lining of the uterus. This sample is then examined under a microscope by a specialist called a pathologist, who looks for cancer cells or other abnormal changes.^[10]

The biopsy is usually performed in the doctor’s office and does not require anesthesia, though some women may be given medication to help them relax. The doctor inserts a thin, flexible tube through the cervix into the uterus and uses suction to collect a small amount of tissue. The procedure takes only a few minutes, though you may feel cramping similar to menstrual cramps during and shortly after the biopsy. Some women also experience light bleeding or spotting afterward.^[10]

An endometrial biopsy is considered the gold standard for diagnosing endometrial cancer because it provides actual tissue that can be analyzed. If the biopsy results show cancer cells, the pathologist can also provide information about the type of cancer and how abnormal the cells look, which helps guide treatment decisions.^[10]

Hysteroscopy

In some cases, doctors may recommend a procedure called hysteroscopy. During hysteroscopy, a thin, lighted instrument called a hysteroscope is inserted through the vagina and cervix into the uterus. This allows the doctor to look directly at the inside of the uterus and see the endometrium. If the doctor notices any abnormal areas, they can use instruments passed through the hysteroscope to take tissue samples for biopsy.^[10]

Hysteroscopy can be done in the doctor’s office or in a hospital, depending on the specific situation. The procedure provides a clear view of the uterine lining and can help identify exactly where abnormal tissue is located. This direct visualization makes it particularly useful when biopsy results are unclear or when a more thorough examination is needed.^[10]

Dilation and Curettage (D&C)

Another procedure that may be used is dilation and curettage, often referred to as a D&C. This procedure is usually performed in a hospital or surgical center, and you will typically receive anesthesia so you do not feel pain. The doctor gently opens (dilates) the cervix and then uses a special instrument to scrape tissue from the lining of the uterus. This tissue is sent to a laboratory for examination.^[10]

A D&C provides a larger tissue sample than a standard endometrial biopsy, which can be helpful if the diagnosis is uncertain or if the doctor needs more information about the extent and type of abnormal tissue present. The procedure is more invasive than an office biopsy, but it provides more comprehensive information.^[10]

Additional Imaging Tests

Once endometrial cancer has been diagnosed through biopsy, doctors may order additional imaging tests to determine whether the cancer has spread beyond the uterus. These tests help establish the stage of the cancer, which describes how far it has spread and helps guide treatment decisions.^[10]

A computed tomography scan, commonly called a CT scan, uses X-rays taken from different angles to create detailed cross-sectional images of the body. These images can show whether cancer has spread to the lymph nodes, liver, lungs, or other organs. A magnetic resonance imaging scan, or MRI, uses powerful magnets and radio waves instead of X-rays to create detailed pictures of soft tissues in the body. MRI scans are particularly good at showing whether cancer has grown into the muscle wall of the uterus or spread to nearby organs.^[10]

A chest X-ray is a simple imaging test that can show whether cancer has spread to the lungs. In some cases, doctors may also order a positron emission tomography scan, or PET scan, which uses a small amount of radioactive sugar injected into the bloodstream. Cancer cells take up this sugar more actively than normal cells, so they show up as bright spots on the scan. PET scans can help identify cancer that has spread to distant parts of the body.^[10]

Blood Tests

While blood tests cannot diagnose endometrial cancer on their own, they provide important information about your overall health. Doctors typically order blood tests before treatment to check your kidney and liver function and to assess your blood cell counts. A test called CA-125 measures the level of a certain protein in the blood that can be elevated in some women with endometrial cancer, though this test is not specific to endometrial cancer and is not used for diagnosis. Instead, it may be used to monitor response to treatment or check for recurrence after treatment is completed.^[10]

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or new ways of using existing treatments for endometrial cancer. Participating in a clinical trial may give you access to promising new therapies that are not yet widely available. However, to ensure that study results are accurate and that participants are safe, clinical trials have specific requirements about who can enroll. These requirements are called eligibility criteria, and meeting them requires undergoing specific diagnostic tests.^[2]

Confirming the Diagnosis

The first requirement for most endometrial cancer clinical trials is having a confirmed diagnosis of endometrial cancer. This means you must have had an endometrial biopsy or a D&C that showed cancer cells when examined under a microscope. The pathology report from your biopsy provides detailed information about the type of cancer cells, how abnormal they appear (called the grade), and other characteristics that help determine if you meet the trial’s criteria.^[4]

Some clinical trials are designed to test treatments for specific types of endometrial cancer. For example, a trial might only accept women with a certain histological type, such as endometrioid adenocarcinoma, serous carcinoma, or clear cell carcinoma. The pathology report from your biopsy will include this information. Other trials may focus on cancers with particular genetic or molecular features, which requires additional specialized testing of your tumor tissue.^[13]

Staging and Imaging Requirements

Clinical trials typically require precise information about the stage of your cancer. The stage describes how far the cancer has spread. Endometrial cancer is staged on a scale from I to IV. In Stage I, the cancer is only in the uterus. In Stage II, it has spread to the cervix. In Stage III, it has spread to the vagina, ovaries, or lymph nodes near the uterus. In Stage IV, the cancer has spread to the bladder, bowel, or organs farther away from the uterus, such as the lungs or liver.^[6][19]

To participate in a clinical trial, you will need imaging tests to determine your cancer’s stage accurately. This usually includes a CT scan of the chest, abdomen, and pelvis or an MRI scan of the pelvis. Some trials may also require a PET scan to look for distant spread of cancer. These imaging studies must be done within a certain time frame before you can enroll in the trial, often within four to six weeks before starting treatment.^[2][10]

Molecular and Biomarker Testing

In recent years, scientists have learned that endometrial cancers can be classified not just by how they look under a microscope, but also by their molecular characteristics. These molecular features can predict how the cancer will behave and which treatments are most likely to work. Many modern clinical trials now require biomarker testing or molecular testing of tumor tissue.^[13]

One important molecular test looks for something called microsatellite instability or MSI. Cancers with high levels of microsatellite instability (called MSI-high) have specific genetic changes that make them more likely to respond to certain types of immunotherapy drugs. Another test looks for changes in genes involved in DNA repair, such as mutations in genes associated with Lynch syndrome. Some trials specifically enroll only patients whose cancers have these molecular features.^[13]

Other molecular tests examine specific proteins found on the surface of cancer cells or look for particular genetic mutations within the tumor. For example, some tests check for mutations in genes called PTEN, PIK3CA, or ARID1A, or for proteins like PD-L1. The presence or absence of these markers can determine whether you are eligible for certain clinical trials testing targeted therapies or immunotherapies.^[13]

Performance Status Assessment

Clinical trials also assess your overall health and ability to carry out daily activities. This is measured using something called a performance status score. One common system is the Eastern Cooperative Oncology Group (ECOG) performance status, which rates your functioning on a scale from 0 to 5. A score of 0 means you are fully active and able to carry on all activities without restriction. A score of 1 means you are restricted in physically strenuous activity but can do light work. Higher scores indicate more severe limitations. Most clinical trials require participants to have a performance status of 0, 1, or 2, meaning they can take care of themselves and are up and about more than half their waking hours.^[4]

Laboratory Tests

Before enrolling in a clinical trial, you will need blood tests to check that your organs are functioning well enough to tolerate treatment. Standard laboratory tests include a complete blood count to measure red blood cells, white blood cells, and platelets; tests to assess kidney function, such as creatinine and blood urea nitrogen; and tests to evaluate liver function, including measurements of liver enzymes and bilirubin. These tests help ensure that your body can safely process and eliminate the study drugs and that you have enough healthy blood cells to withstand treatment.^[4]

Some trials have specific cutoff values for these laboratory results. For example, a trial might require that your white blood cell count be above a certain level or that your kidney function tests fall within a particular range. If your test results do not meet these criteria, you may not be eligible for that particular trial, though there may be other studies with different requirements.^[4]

Additional Testing for Specific Trials

Depending on the specific clinical trial, you may need additional tests. For trials studying drugs that affect the heart, you might need an electrocardiogram (ECG) or an echocardiogram to check your heart function. Trials testing immunotherapy drugs sometimes require tests to assess your immune system function. Some studies require pregnancy testing for women of childbearing age, as many cancer treatments can harm a developing fetus.^[4]

Understanding which tests you need and why they are required can help you navigate the clinical trial enrollment process. Your study coordinator and research team will guide you through each step and explain the purpose of each test. If you do not qualify for one clinical trial based on your diagnostic results, there may be other trials for which you are eligible, so it is always worth discussing options with your healthcare team.^[2]