Prostate Cancer Tests

Abnormalities in either a digital rectal exam or PSA (prostate specific antigen) test raise the suspicion of cancer in most cases, and further tests such as transrectal ultrasound and prostate biopsy are then required. Diagnosing prostate cancer at an early stage can be difficult with a digital rectal exam alone, because the cancer cells tend to spread diffusely through the prostate and into surrounding tissues, rather than forming a solid mass, as do most other forms of cancer.

This section includes information on:

• Prostate specific antigen (PSA) test
• Digital rectal exam
• Transrectal ultrasound
• Prostate biopsy
• Gleason score
• Staging tests
• Testing and prostatic intraepithelial neoplasia (PIN)
• Other tests

Prostate specific antigen (PSA) test

The PSA test was first approved by the FDA in 1986 as a way to determine whether prostate cancer had been treated successfully and to monitor for its recurrence. However, PSA tests are now FDA approved for detection and are widely used to screen for the presence of prostate cancer. Clinical studies have demonstrated the following benefits of PSA testing:

• An elevated PSA is the single best predictor of the presence of prostate cancer.
• PSA testing detects prostate cancer about five to 10 years earlier than digital rectal exams.
• Most cancers detected with PSA testing are curable.
• Serial PSA testing of a population leads to virtual elimination of advanced prostate cancer at the time of diagnosis.

However, it is not clear whether using the PSA test to screen for prostate cancer actually reduces the risk of death from the disease. In addition, some men with an elevated PSA do not have prostate cancer, and some of the cancers detected by the PSA test are too small or too slow growing to be life threatening. These men may undergo unnecessary diagnostic tests and treatments and may experience undue anxiety. Consequently, men should discuss the benefits and drawbacks of PSA testing with their physician before having their PSA levels measured.

This section includes information on:

• Testing guidelines
• Test results and cancer risk
• Refinements to the test

Guidelines

The American Cancer Society and the American Urological Association recommend an annual PSA test beginning at age 50. Men at increased risk for prostate cancer—black men and men with a family history of the disease—should begin annual screening at age 40 to 45. A recent study found that testing all men at age 40, age 45, and then every other year after age 50 may be a better strategy—it saved more lives and was less expensive. Another recent study suggests that men age 50 and older who have PSA levels below 2 ng/mL do not need annual testing.

A number of factors may affect the results of a PSA test. For example, some studies show that ejaculation one or two days before a PSA test may increase PSA levels in the blood. Consequently, men should abstain from sex for two days prior to a PSA test. Digital rectal exams and biopsies of the prostate may also affect PSA levels, though the increase in PSA caused by a digital rectal exam is not thought to be significant enough to result in a false-positive test result. In addition, other prostate problems (such as benign prostatic hyperplasia or prostatitis) can inflate PSA levels, and BPH medications (such as finasteride and dutasteride) can lower PSA levels by about 50 percent.

Risk of cancer

PSA is an enzyme produced almost exclusively by the glandular cells of the prostate. It is secreted during ejaculation into the prostatic ducts that empty into the urethra. PSA liquefies semen after ejaculation so that sperm are released. Normally, only very small amounts of PSA are present in the blood. But an abnormality of the prostate can disrupt the normal architecture of the gland and create an opening for PSA to pass into the blood stream. Thus, high blood levels of PSA can indicate the presence of cancer. The percentage risks of cancer based on PSA levels are as follows:

• PSA levels under 4 nanograms per milliliter (ng/mL) are "normal" at age 50 and older; levels below 2.5 ng/mL are "normal" at age 40 to 49. These levels are associated with less than a 15 percent to 19 percent risk of cancer;
• 4 to 10 ng/mL, 20 percent to 30 percent risk;
• 10 to 20 ng/mL, 50 percent to 75 percent risk;
• above 20 ng/mL, 90 percent risk.

Improvements to the PSA

Researchers have developed several ways to improve the ability of PSA to detect prostate cancer. These refinements include:

• Assessing PSA in relation to prostate size (PSA density)
  PSA density takes into account the size of a man's prostate when evaluating his PSA level. It is calculated by dividing the PSA value by the size of the prostate (as determined by transrectal ultrasound). This measurement helps doctors distinguish between benign prostatic hyperplasia (BPH) and cancer: The higher the PSA density, the greater the chance of cancer, because elevated PSA is less likely the result of prostate enlargement. According to several studies, a PSA density greater than 0.15 indicates a higher risk of cancer. PSA density appears most useful for diagnosing prostate cancer in men with PSA levels between 4 and 10 ng/mL.
• Monitoring annual changes in PSA (PSA velocity)
  This measurement takes into account annual changes in PSA values, which rise more rapidly in men with prostate cancer than in men without the disease. A study found that an increase in PSA levels of greater than 0.75 ng/mL per year was an early predictor of prostate cancer in men with PSA levels between 4 and 10 ng/mL. PSA velocity is especially helpful in detecting early cancer in men with mildly elevated PSA levels and a normal digital rectal exam; it is not useful in predicting the presence of cancer unless changes in PSA are evaluated over at least 1 1/2 to 2 years.
• Measuring the ratio of free to total PSA (percent free PSA)
  PSA in the blood is either bound (attached to proteins) or unbound (free). Men with prostate cancer have a higher percentage of bound PSA and a lower percentage of free PSA than men with benign prostatic hyperplasia (BPH). Research suggests that determining the ratio of free to total PSA in the blood helps distinguish between PSA elevations due to cancer and those caused by BPH. In men with PSA levels between 4 and 10 ng/mL, performing a prostate biopsy only when the percent free PSA is 24 percent or below would result in the detection of 90 percent of prostate cancers and reduce by 20 percent the number of unnecessary biopsies. Percent free PSA, as well as PSA density and PSA velocity, can also be used to determine the need for a repeat biopsy when the initial biopsy shows no evidence of cancer but cancer is still suspected.
• Adjusting PSA for a patient's age (age-specific PSA)
  PSA increases with age because the prostate gradually enlarges as men grow older. Some years ago, researchers suggested adjusting PSA levels for the age of the patient: Higher levels would be considered normal in older men and lower levels considered normal in younger men. However, research has not shown that using lower levels to prompt biopsy in younger men increases the likelihood of finding curable cancers, nor that using higher levels in older men interferes with the chance of detecting curable cancers. For now, a level of 4 ng/mL is considered the upper limit of normal in men age 50 and older. For men younger than age 50, the upper limit of normal is 2.5 ng/mL.

Digital rectal examination

Because the prostate cannot be seen or felt externally, doctors perform a digital rectal exam (DRE) to assess its size, shape, and consistency. Along with prostate specific antigen (PSA) testing, a DRE is an essential screening tool for prostate cancer.

The American Cancer Society and American Urological Association recommend that all men over age 50 have a DRE and a PSA test at least once a year. Men at high risk for prostate cancer—black men and any man with two or more first-degree relatives (father or brothers) with the disease—should begin annual DRE and PSA screening at age 40 or 45. Despite this recommendation, a study published in the Archives of Internal Medicine in 2004 found that only 47 percent of 588 men who underwent PSA testing had a DRE performed along with it. Skipping this exam means that many men with prostate cancer and a normal PSA result will go undiagnosed.

Some men avoid getting a DRE because they feel uncomfortable about the procedure, but it is not painful and lasts less than a minute. During a DRE, the patient either bends forward over the examination table, lies on his side, or kneels on the table. The doctor then inserts a gloved, lubricated finger a few inches into the rectum and gently palpates the prostate gland to feel for a nodule or lump, change in size, hard tissue, or any other abnormality that might indicate a tumor is present.

The frequent absence of a solid, palpable mass makes it difficult to detect early prostate cancer with a digital rectal exam. Used alone, a digital rectal exam misses 30 percent to 40 percent of prostate cancers, and most cancers found with the exam are detected when it is too late for treatment to be effective. The most reliable way to detect prostate cancer in its early stages is to combine digital rectal exams with measurements of PSA levels in the blood.

Transrectal ultrasound

If the results of a digital rectal exam, a PSA test, or both are suspicious for cancer, transrectal ultrasound is used to determine the size of the prostate, identify areas of possible cancer, and direct the needles used for prostate biopsy. The procedure takes 15 to 20 minutes and is performed on an outpatient basis. Some physicians use a local anesthetic such as lidocaine (Xylocaine) to reduce discomfort during the procedure. While the patient is lying on his side, an ultrasound probe (about the size of a finger) is gently inserted 3 to 4 inches into the rectum. The probe emits sound waves that are converted to video images. The images are generated with the probe in several positions as it is gradually withdrawn from the rectum.

Prostate biopsy

When prostate cancer is suspected, either from the results of a digital rectal exam, a PSA test, or both, a prostate biopsy is performed. The procedure involves taking samples of prostate tissue and examining them under a microscope for the presence of cancer. Each year, about 800,000 men undergo prostate biopsy.

The most common biopsy method is transrectal ultrasound-guided biopsy, also known as TRUS. The procedure is usually done in a urologist's office and takes about 20 minutes to perform. While the patient is lying on his side, an ultrasound probe is inserted into the rectum to visualize the prostate. Fitted to the probe is a biopsy gun that drives small needles through the wall of the rectum and into the prostate. In less than a second, the needle removes a small tissue sample. Usually, eight to 12 tissue samples are taken throughout the prostate.

After the procedure, the tissue samples are sent to the laboratory to be examined under a microscope by a pathologist. The results are usually ready in three to five days. Nearly 75 percent of the time, no prostate cancer is detected in the samples, usually because the elevated PSA levels that prompted the biopsy were due to another prostate condition (such as BPH or prostatitis) or a nonmedical reason (such as recent sexual activity). A second biopsy is required when the pathologist finds atypical cells (cells suspicious but not diagnostic of cancer) or when the biopsy does not indicate cancer but the results of the digital rectal exam or PSA test were highly suggestive of cancer.

Many men worry that prostate biopsy will be painful, but it usually causes only minor discomfort. Common side effects include minor rectal bleeding; blood in the stool, urine, or semen; and soreness in the biopsied area. All of these side effects disappear with time.

Gleason score

A malignant (cancerous) tissue specimen is assigned a Gleason score—the most important factor in predicting the state of the disease and the probable outcome. The Gleason score is the sum of the grades of the two most prevalent malignancy patterns in the specimen. Assigned by the pathologist, these grades characterize the tumor and describe how closely the malignant cells resemble the normal ones. Grades range from 1 to 5, with 1 being the closest to normal and having the least potential to spread. A Gleason score of 7 results from a grade of 3 for the predominant pattern of cancer cells and a grade of 4 for the secondary one. You may also find the percentage of each grade in your pathology report, but the Gleason score is the most commonly reported.

Staging tests

Determining the extent of prostate cancer is important in predicting the course of the disease and choosing the best treatment. The results from the digital rectal exam, PSA tests, and prostate biopsy give the urologist a good idea of whether the cancer is confined to the prostate or has spread outside the gland.

In some cases, patients may undergo a bone scan to determine whether prostate cancer has spread to the bones. The bone scan involves an intravenous injection of a radioactive material, which settles in damaged bone. (Bone can be damaged by cancer as well as by arthritis and other bone diseases.) A special scanner is then used to detect the radioactivity. Areas of the body with increased radioactivity have bone damage, possibly because cancer has spread to the bone.

A test called the ProstaScint scan is also available to detect prostate cancer cells that have spread, in this case to the lymph nodes or soft organs. ProstaScint uses antibodies that attach to a protein, called prostate specific membrane antigen, on prostate cancer cells. These antibodies mark cancer cells with a radioactive isotope that is then picked up by a special scanner. The ProstaScint scan is not considered to be very accurate. It is usually used when PSA levels start to rise again after surgery or radiation therapy.

Computed tomography (CT) or magnetic resonance imaging (MRI) may be done to look for enlarged lymph nodes if the spread of cancer is suspected. In some cases, the urologist may recommend a laparoscopic biopsy, in which a surgeon uses a laparoscope (an instrument with a light and a camera) to view the lymph nodes near the prostate.

Testing and PIN

A prostate biopsy that reveals prostatic intraepithelial neoplasia (PIN) may leave men unsure of how to react. Although PIN is thought to be a pre-malignant lesion that has the potential to evolve into cancer, it is not cancer itself. But certain men with this finding require careful follow-up because sometimes a second biopsy will reveal a previously undiagnosed tumor. Approximately 9 percent of men who have a prostate biopsy in the United States will be diagnosed with high-grade PIN, which translates to approximately 115,000 men every year.

There is controversy among experts as to the appropriate follow-up of men with high-grade PIN. Some studies have shown that men with high-grade PIN are at higher risk of having prostate cancer and should undergo a repeat biopsy. However, several well-designed studies suggest that men with a diagnosis of high-grade PIN have the same risk of prostate cancer as men who have no abnormal findings on a biopsy. If a man with high-grade PIN had a well-performed, extended biopsy that included sampling of the entire peripheral zone of the prostate, then a repeat biopsy is not mandatory. A reasonable follow-up plan would be a digital rectal examination and yearly or biennial testing of PSA levels.

Some evidence suggests that PIN lesions may be part of a multistep process that leads to invasive prostate cancer since PIN shares many of the genetic hallmarks of "true" prostate cancer. Men with high-grade PIN should continue to have their PSA levels checked and undergo periodic prostate exams. They should also keep their weight under control, exercise regularly, and eat a low-fat diet rich in fruits, vegetables, and fiber.

Other tests

Other routine tests include urinalysis and blood tests for anemia. If surgery is contemplated, general health status—particularly cardiovascular and pulmonary function—is assessed to decide whether the man is a suitable candidate for surgery.