How Is Prostate Cancer Diagnosed?

Prostate cancer develops when abnormal cells in the prostate gland (a small gland that helps with semen production in people assigned male at birth) grow out of control and form a tumor.  Most people with prostate cancer are diagnosed before symptoms occur after routine screening tests. Prostate cancer is a slow-growing disease and does not usually cause symptoms in the early stages.

When prostate cancer causes symptoms, a doctor will perform a digital rectal exam and order blood tests to look for signs of a tumor. If a mass is discovered or suspected, you may be referred to a urologist—a doctor who specializes in conditions that affect the urinary tract and reproductive systems. The urologist will use imaging tests and perform a prostate biopsy to diagnose prostate cancer.

In this article, we’ll take a look at how prostate cancer is diagnosed, including the various tests and procedures used to confirm the diagnosis. 

Medical History 

When you visit your healthcare provider, they will ask about any prostate cancer symptoms you have and how long you’ve had them. They will also ask questions to determine what risk factors you may have for prostate cancer.  A family history of the disease, age, and exposure to certain chemicals (such as agricultural chemicals) are known risk factors.

Digital Rectal Exam (DRE)

If you have symptoms of prostate cancer or risk factors for the disease, your healthcare provider may perform a digital rectal exam (DRE). This involves your doctor inserting a gloved, lubricated finger into your rectum to feel the prostate and detect any abnormalities. Bumps, hard areas on the prostate, or an enlarged or irregularly shaped prostate are possible signs of prostate cancer that will require further investigation.

Prostate-Specific Antigen (PSA) Blood Tests

A blood test that measures the amount of prostate-specific antigen (PSA)—a protein made by cells in the prostate gland—is the standard screening test for prostate cancer. Both healthy cells and cancer cells produce PSA, but cancer cells tend to produce higher levels of it. If a PSA test indicates elevated levels of PSA in the blood, this can be a sign of prostate cancer. 

There is no specific PSA number that definitively indicates prostate cancer. There are ranges that are considered ‘normal’ or ‘high’:

• Normal range: PSA levels below 4 nanograms per milliliter (ng/mL) are generally considered normal. Levels higher than 4 ng/mL may indicate prostate cancer. However, about 15% of people with a PSA below 4 are diagnosed with prostate cancer if a biopsy is performed. 
• Borderline range: About 25% of people with PSA levels between 4 and 10 have prostate cancer. 
• High range: People with a PSA above 10 have a 50% chance of having prostate cancer. 

Other factors besides prostate cancer can affect PSA levels. For example, benign (non-cancerous) conditions such as prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (enlarged prostate) are associated with high levels of PSA. Certain medications and older age can consistently raise PSA levels, while recent ejaculation and even activities like riding a bicycle can temporarily raise PSA levels.

For these reasons, PSA alone cannot be used to diagnose prostate cancer. If your PSA test results indicate elevated PSA levels in the blood, your healthcare provider may repeat the test in a couple of weeks to determine if the levels are still high or have increased. Or, they may order different types of PSA tests:

• PSA velocity: This measures how quickly PSA increases over time. A rapid increase may suggest cancer. However, this test is not recommended as a reliable diagnostic tool. 
• Percent-free PSA: This is the percentage of PSA in the blood that is not attached to proteins. A free-PSA test may be ordered if your initial PSA results are in the borderline range (between 4 and 10). A low percentage of free PSA means that you have a higher chance of having prostate cancer. 
• PSA density: People with large prostates have higher PSA levels. This test measures the size (volume) of the prostate gland and divides the PSA number by the prostate volume. Higher PSA density is associated with a greater likelihood of prostate cancer. 
• ProPSA: This measures the number of precursors of prostate-specific antigen, which are released from cancerous cells and tissues.
• Age-specific density: PSA levels are often higher in older men. Some doctors compare PSA results with the results of other men of the same age.

Prostate Health Index (PHI) 

The Prostate Health Index (PHI) is a calculation that combines the total PSA, free PSA, and proPSA measurements to help doctors determine the likelihood of detecting prostate cancer with a biopsy. Research suggests that the PHI can be an effective tool for screening for prostate cancer and help prevent unnecessary biopsy procedures. It may also help doctors such as an oncologist (medical doctors who specialize in cancer) determine the best treatments when prostate cancer is diagnosed. 

Transrectal Ultrasound (TRUS)

A transrectal ultrasound (TRUS) is an imaging test that allows doctors to see the prostate gland to look for signs of cancer. To perform the test, a thin ultrasound probe is inserted into the rectum. The probe uses sound waves to take a picture of the prostate gland. You will be given an enema before the procedure, and may feel mild discomfort during the ultrasound. 

If a mass or other abnormalities are detected on the prostate during a TRUS, a biopsy is required to determine if the mass is cancerous. A biopsy is often performed at the same time as the TRUS procedure.

Prostate Biopsy 

If the PSA, DRE, or other tests indicate the possible presence of prostate cancer, a biopsy will be recommended. During a biopsy, a small tissue sample is removed from the prostate and taken to the lab, where it is examined under a microscope to check for cancer cells.

A core needle biopsy is the most common method used to diagnose prostate cancer. The doctor removes tissue samples by inserting a thin needle into the prostate. This may be done through the wall of the rectum (transrectal biopsy) or through the skin between the anus and scrotum (transperineal biopsy). The needle is then removed with a small sliver of prostate tissue. This process is repeated about 12 times to take tissue samples from different parts of the prostate. 

The prostate biopsy procedure takes about 20 to 30 minutes, and you will be given anesthesia beforehand to numb the area. If a transrectal biopsy is performed, you may be given antibiotics afterward to reduce the risk of infection. Once all of the samples have been retrieved, a pathologist—a doctor who specializes in evaluating cells, tissues, and organs—will examine it under a microscope to look for cancer cells. 

MRI Fusion Biopsy 

Magnetic resonance imaging (MRI) scans create detailed pictures of the body using strong magnets and radio waves. An MRI can provide very clear pictures of the prostate and nearby tissues and can help doctors determine if a mass is malignant (cancerous) or benign.

An MRI fusion biopsy combines an MRI scan, transrectal ultrasound (TRUS), and biopsy into one procedure. First, an MRI is performed to look for signs of cancer on the prostate. Then, the TRUS is performed. Computer software combines pictures from both the MRI and TRUS to produce 3D images that help target the specific area where a tissue sample will be retrieved (biopsy).

The tissue samples are then sent to the lab where they will be checked under a microscope for cancer cells. 

Multiparametric MRI (mp-MRI) 

Multiparametric MRI (mp-MRI) is a technique that helps doctors more easily identify cancer in prostate tissue. This procedure may also give an idea of how aggressive the cancer is, meaning how quickly it will grow. It can also help identify if the cancer has spread to surrounding tissues near the prostate or other areas of the body. 

For this procedure, a standard MRI is performed and then one other type of MRI (e.g., diffusion-weighted imaging or dynamic contrast-enhanced) is done so doctors can compare images from the two imaging tests to help find abnormalities in the prostate.

Stages of Prostate Cancer

The stage of prostate cancer describes where the cancer is located, whether it has spread, and where (how far) in the body it has spread. Staging helps oncologists develop a treatment plan and determine a person’s chances of recovery (prognosis). 

There are two types of staging for prostate cancer:

• Clinical staging: This is based on results of the digital rectal exam (DRE), prostate-specific antigen (PSA) test, imaging tests, and a Gleason score (grade of the tumor). Doctors also use these results to determine whether further diagnostic tests (e.g., MRI) are needed. 
• Pathologic staging: If you have prostate surgery to remove part of or the entire prostate gland, doctors can examine the cancer cells to learn more about the disease. This may help them determine the most effective treatments for you.

Clinical staging is completed at the time of diagnosis. Pathologic staging is done after surgery. Pathologic staging is usually more accurate since it happens after the prostate tissues have been removed and thoroughly examined in the lab. 

Gleason Score Grading 

When pathologists examine prostate cancer cells under a microscope, they give it a Gleason score and grade based on how much the cancer looks like healthy tissue. The lower the score, the more cancer cells look and act like healthy cells. A higher score indicates aggressive cancer that is more likely to grow and spread quickly.

• Gleason 6 or lower: Cancer cells look similar to healthy cells and are likely to grow and spread very slowly. 
• Gleason 7: Cancer cells look somewhat similar to healthy cells and are likely to grow and spread slowly. 
• Gleason 8-10: Cancer cells look very different from healthy cells and are likely to grow and spread quickly. 

Clinical Staging of Prostate Cancer 

At the time of diagnosis, prostate cancer is clinically staged using the TNM system, which is based on 5 different factors:

• The extent of the primary tumor (T)
• Whether cancer has spread to lymph nodes near the prostate (N)
• Whether cancer has metastasized (spread) to more distant parts of the body (M)
• PSA levels at the time of diagnosis 
• The Gleason score/grade of the tumor

Prostate cancer stages include:

• Stage 1: Cancer is slow-growing, and the tumor is confined to only one-half of one side of the prostate. The tumor cannot be felt during a DRE, PSA levels are low, and cancer cells resemble healthy cells under a microscope. 
• Stage 2: The tumor is confined to the prostate, and may be felt during DRE. PSA levels range from medium to low. At this stage, the tumor is small but may grow and spread. 
• Stage 3: The tumor is large and has spread outside of the prostate gland into nearby tissues or organs, such as the bladder or rectum. PSA levels are high and the tumor is likely to grow and spread. 
• Stage 4: Cancer is advanced and has spread beyond the prostate to nearby lymph nodes as well as other, more distant parts of the body. 

Screening for Related Conditions

Some conditions that affect the urinary tract and prostate gland cause symptoms similar to that of prostate cancer. Tests and procedures help your doctor determine whether your symptoms are caused by cancer or another condition, such as:

• Benign prostatic hyperplasia (BPH): Enlarged prostate that is common in older men
• Prostatitis: Inflammation of the prostate gland that is usually caused by an infection
• Urinary tract infection: An infection in any part of the urinary system (bladder, kidneys, urethra)
• Prostatic stones: Nodules (stones) that develop in or around the prostate gland due to BPH or prostatitis
• Urethritis: Inflammation of the urethra
• Bladder cancer. Cancer that begins in the cells of the bladder

A Quick Review

Prostate cancer is often detected through screening tests, such as the prostate-specific antigen test and a digital rectal exam, before symptoms develop. Imaging tests—including transrectal ultrasound and MRI—are used to look for signs of cancer in the prostate and nearby tissues. A biopsy (removal of small tissue samples from the prostate) can confirm a diagnosis and help oncologists determine the stage and grade of the cancer.