Prostate Cancer: Testing
Prostate cancer is the most common non-skin cancer in men in the United States, and the second leading cause of cancer death in men. Strategies for managing prostate cancer focus on early detection. Prostate-specific antigen (PSA) is a known tumor marker currently used for early detection of prostate cancer. The American Urological Association (AUA) recommends a discussion of the risks and benefits of prostate cancer screening before a man has a PSA test. In men who wish to be screened, the AUA recommends getting a first or baseline PSA at age 40.
A prostate biopsy to confirm the presence of prostate cancer should be considered based on findings from both the PSA test, and a physical exam of the prostate with a digital rectal exam (DRE) according to the AUA. Before recommending a biopsy, your health care provider should take into account a number of factors. These include your PSA level, your age, how quickly your PSA level rose—known as PSA velocity—the amount of PSA in your blood compared to the size of your prostate. known as PSA density, your family history of prostate cancer, your race, any prior prostate biopsy history and other health problems (known as co-morbidities) as well as your general health.
The American Urological Association Foundation (AUA Foundation) is concerned that recent studies about prostate-specific antigen (PSA) testing may present conflicting information to patients about the value of this critical prostate-cancer screening test. The benefits of regular screening and early detection should not be discounted in the overall population.
A body of evidence exists that supports the value of this test and that screening has the potential to save lives. The AUA Foundation strongly believes that the decision to screen is one that a man should make in conjunction with his physician and supports the screening recommendations of the American Urological Association.
What is PSA?
Prostate-specific antigen (PSA) is a substance produced by the prostate gland. With prostate disease, inflammation, or trauma, greater amounts of PSA enter a man’s blood stream. This elevated blood PSA level has become an important marker of many prostate diseases, including benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer.
The Use of PSA for Early Detection of Prostate Cancer
PSA testing is one of several measures used to assess the risk of prostate cancer. If your PSA is high for your age or steadily rising, with or without an abnormal physical exam of your prostate with a DRE, a biopsy may be recommended. Your health care provider will use your PSA test and other information to help guide treatment options (including active surveillance, androgen ablation therapy, cryotherapy, laparoscopic radical prostatectomy, open radical prostatectomy, radiotherapy, robotic-assisted radical laparoscopic prostatectomy and radical prostatectomy). if you are diagnosed with prostate cancer (Figure 1 shows the options available at each stage of prostate screening). In a prostate biopsy, tiny pieces called cores of prostate tissue are removed for examination under a microscope. The biopsy helps determine if cancer or other abnormal cells are present in the prostate.
If the biopsy shows prostate cancer is present, other measures provide valuable information you and your health care provider can use to decide which treatment if any, is best for you. These other measures include information obtained from the biopsy itself such as: the Gleason score; an estimation of the extent of the cancer known as the clinical stage; an estimate of the amount of cancer in your prostate- known as tumor volume-; the number of positive biopsy cores and the extent of cancer within those cores. These factors provide your healthcare provider and you valuable information to help guide your treatment decisions.
What is the Gleason Score?
The most common system to evaluate and describe prostate cancer currently in use is the Gleason grading system. After a biopsy, the pathologist assigns a primary grade from 1 to 5, with 5 being the most aggressive, to the pattern of cancer cells occupying the greatest area of the biopsy cores. A secondary grade is assigned to the pattern occupying the second largest area. These two grades added together determine the Gleason score. This score ranges from 2 to 10. It is generally agreed that tumors with a Gleason score of 2 to 4 are very uncommon but have a very low biological aggressiveness. Scores of 5 to 6 have low aggressiveness. Those men with a Gleason score equal or greater than 7 have more biologically aggressive tumors. Those with primary scores of 3 and secondary scores of 4 are thought to have intermediate aggressiveness. Primary Gleason grades of 4 or 5 are an indication of aggressive prostate cancer.
Figure 1: What a man can expect from prostate cancer screening
FACTORS TO CONSIDER ABOUT PROSTATE SCREENING
1. The goal of early prostate cancer detection.
The goal of early detection is to reduce death from prostate cancer in men. Early stage prostate cancer has many options for treatment and cure, including active surveillance. Men should have a thorough discussion with their healthcare provider on which particular treatment option is right for them, weighing the benefits and disadvantages of each. Even men with very advanced cancer may benefit from treatment and should discuss their options with their healthcare provider.
2. The proportion of clinically significant or higher risk prostate cancer detected with PSA is unknown.
There is currently no universally accepted definition of what identifies prostate cancer as either life threatening or insignificant. Ideally, the characteristics of each man’s prostate cancer will guide an informed discussion between the man and his doctor. This may avoid unnecessary or aggressive therapy in certain men. Health care providers use tools (i.e. nomograms, probability tables, etc) to help predict the likelihood of various long-term outcomes with or without treatment for men with prostate cancers.
3. Men who wish to be screened for prostate cancer should have both a PSA test and a DRE.
While blood PSA levels are currently the best single test for early prostate cancer detection, the DRE can also identify men with prostate cancer. Evidence from research studies suggests that combining both tests improves the overall rate of prostate cancer detection.
4. A variety of factors can affect PSA levels and should be considered in the interpretation of results.
The three most common prostate diseases—prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer—may cause elevated PSA levels in the blood. Treatment with antibiotics will decrease PSA by approximately 30% in men whose PSA elevation is due to prostatitis alone. Other medications, treatments or trauma (which can include a prostate biopsy or cystoscopy) to the prostate can affect PSA test results. A man should talk to his health care provider about any treatments he may have received or medications and supplements he may be taking.
PSA results can vary 20-25% depending upon the type of assay each laboratory uses for their PSA test. For this reason, it is important for a man and his health care provider to know which type of assay is used the PSA test and to use the same type of assay for every PSA test he has.
5. For patients choosing to undergo PSA testing, several important factors may influence results.
- PSA velocity: Changes in PSA levels over time or PSA velocity (PSAV) is used to assess both cancer risk and aggressiveness. It is recommended at least three PSA tests should be done over a period of at least 18 months to correctly measure PSAV.
- Age: Because blood PSA levels tend to increase with age, the use of higher "normal" levels for older men results in fewer biopsies. Table 1 shows "normal" PSA ranges for different age groups, based upon the ethnic backgrounds of men.
Normal* PSA Ranges for Men at Different Ages
*Based on reviews of research, normal ranges for men in these age groups by race
**PSA is measured in nanograms per milliliter.
- Free PSA: PSA exists in the blood two ways. The PSA test measures the total amount of PSA in the blood that is bound to plasma proteins. A different test can measure the amount of PSA present in the blood in a free state, called free PSA. Non-cancerous prostate tissue contains more of the free PSA than prostate cancer tissue. Men with prostate cancer tend to have lower free-to-total ratios. Men with other prostate disease that is not cancer usually have higher free-to-total ratios. Knowing the ratio of free-to-total PSA values can help identify men who may not need to have a biopsy.
- Prostate volume: Larger prostates produce larger amounts of PSA. Adjusting the PSA value for the size of the prostate can also reduce need for a biopsy. Knowing the impact of prostate size on the PSA value may improve PSA's ability to identify cancer.
A nomogram is a prediction tool that is based on statistics that can help determine the need for a biopsy. It combines clinical and pathologic factors known to have an impact on outcome from prostate cancer. Prostate nomograms are designed to help physicians and patients decide which treatment approaches will result in the greatest benefit.
6. When should a man have a prostate biopsy?
Although an abnormal DRE or an elevated PSA test may suggest the presence of prostate cancer, a biopsy test identifies actual cancer cells in the prostate tissue. Cancer is confirmed by a pathologist's examination of prostate tissue from the biopsy. Higher values of PSA are associated with a higher risk of prostate cancer. Because of this, the AUA is not recommending a single, minimum PSA test value, to suggest the need for a prostate biopsy. The decision to proceed with a prostate biopsy should be based primarily on PSA and DRE results.
However it should also take into account the factors mentioned earlier, plus a man's family history of prostate cancer, his race, any prior biopsy history and other significant health issues he may have. These factors may also identify which men might have a "significant" or life threatening prostate cancer and should have a biopsy.
Prostate biopsy for diagnosis of prostate cancer can be obtained in several ways. The most common method is by means of a transrectal, ultrasound-guided prostate biopsy. A doctor usually performs a biopsy as an outpatient procedure with local anesthesia. Most prostate biopsies collect samples of tissue (at least 8 to 12 cores) from the different areas of the prostate. The pathologist looks at these cores to see if any cancer cells are present. The risks and benefits of a biopsy should be discussed with a health care provider.
7. PSA level in a man's blood is generally a good predictor of the risk of prostate cancer, the extent of the cancer, and the long-term outcomes after treatment of the cancer.
What is the likelihood a man has prostate cancer if he has a high PSA? The answer depends on the level of PSA in the blood and the rate at which it is rising. Men whose PSA levels rise sharply over a short period are more likely to have prostate cancer than those who do not see significant changes in their PSA velocity.
The PSA level and the rate at which it is rising relate to the extent of the cancer as well as how aggressive the prostate cancer may be. The PSA velocity can also help your health care provider predict what a man’s potential outcomes may be if he chooses treatment.
8. The decision to use PSA for the early detection of prostate cancer should be individualized. Patients should be informed of the known risks and the potential benefits of early screening.
Prostate cancer deaths have recently been declining in the United States. Research is underway to determine if the possible reduction in morbidity and death from early diagnosis of prostate cancer is sufficient to outweigh the cost and potential consequences sometimes associated with disease treatment. A diagnosis of advanced prostate cancer is associated with significant health consequences and death.
Treatment procedures for localized prostate cancer include surgery (radical prostatectomy), radiotherapy (external beam radiation, proton beam radiation, or interstitial prostate brachytherapy), or cryotherapy. These treatments all carry a risk of complications. Potential complications of active treatments include erectile dysfunction, urinary incontinence, and bowel symptoms.
Decisions regarding early detection of prostate cancer through screening should be tailored to each man. The benefits and consequences should be discussed with his health care provider before PSA testing occurs. Not all men are appropriate candidates for screening efforts for this disease. Ideally, health care providers should consider a number of factors, along with the man’s preferences. Screening in men with less than a 10-year life expectancy, either due to age or other illness or disease, is discouraged.
It is not known with certainty that that the use of PSA testing decreases the risk of dying of prostate cancer. Screening with PSA does result in identifying more cancers than would be detected without the use of PSA. However, many of these cancers may be small and very slow growing. Such cancers may not pose a threat to them men who have them. This is sometimes called over detection. If men who have such cancers are uniformly treated, many men may suffer the side effects of treatment without the benefit of a longer life (called over treatment). Prostate biopsy is associated with a small risk of side effects such as bleeding or infection. A limited number of men may find the biopsy very painful. All men considering biopsy should understand the risks of the biopsy itself as well as the risks of over detection and over treatment.
9. Early detection and risk assessment of prostate cancer should be offered to men 40 years of age or older who wish to be screened.
Previously, some groups have recommended that early detection begin at age 50 years for men at average risk of prostate cancer, or sooner for those men at higher life time risk (positive family history, African American race). Although family history of prostate cancer leads to a higher risk of prostate cancer diagnosis, it is not associated with an increased risk of high grade disease. Among men in their 40s and 50s, a baseline PSA level above the middle value see for men their age is a stronger predictor of future risk of prostate cancer than family history or race. This is because prostate enlargement is less likely to influence the PSA value in younger men compared to older men.
One way to identify this high-risk group of men with a PSA level above the middle value in their 40s is to begin testing at age 40 years. This establishes a baseline PSA value. It can be used to determine future screening intervals based upon the PSA value results. Men in their 40s with a PSA value above 0.6 to 0.7 ng/mL are at higher risk for prostate cancer.
Although prostate cancer is not detected often below age 50 years, there are a number of reasons to offer early detection prior to age 50. Since death from prostate cancer occurs, on average, 15 to 20 years after diagnosis of an early cancer, men dying at age 55 to 64 likely could have been cured by diagnosis and effective treatment prior to age 50. When compared to men older than 50, younger men are more likely to have prostate cancer that can be cured. Infrequent testing of men in their 40s and after age 50 might reduce prostate cancer deaths and the cost of screening when compared to annual testing beginning at age 50 years. Knowing a man’s baseline PSA values in his 40s to compare with future PSA tests after he turns 50 could help identify those men with life threatening prostate cancer at a time when cure is still possible.
How often he should be screened should be based on the results of the PSA test since the future risk of prostate cancer is closely related to the PSA level. Research suggests that most cancers detected at two to four years after a first PSA/DRE screen are likely to be cured with treatment.
PSA screening is common among the men over age 70. These men may have limited life expectancies. Because of the long natural history of most prostate cancers and competing causes of death in men that age, the benefits of screening may decline as a man grows older. Each man’s health care provider should assess his health status to determine if he should have PSA testing at any given age.
In 2008, the U.S. Preventative Services Task Force issued guidelines, which recommend against screening men over age 75. This recommendation estimates the age at which the average American man has ten years or less life expectancy, but the recommendation for PSA screening should be individualized. This is especially true in men with excellent health, absence of other serious health concerns, and a history of long life in their family.
High-risk prostate cancer rates do in fact increase with age, accounting for 43% of cancers diagnosed in men older than 75 years vs. 25% among men less than 75 years. It is important to understand the difference between screening for prostate cancer and treatment of prostate cancer. A diagnosis of prostate cancer in this age group (over 75 years) may be informative for a man’s overall health but may never require treatment beyond active surveillance. Conversely, men with aggressive prostate cancer in this age group should not be denied the opportunity for diagnosis and treatment, which could affect their length and quality of life.
What is active surveillance? Active surveillance describes a type of close follow up performed on men with prostate cancer. Is usually consists of serial PSA, DRE, transrectal ultrasounds, and repeat prostate biopsies at regular intervals. It is different from watchful waiting in that men on active surveillance may elect treatment for cure when their disease appears to be changing and becoming more aggressive. Men on watchful waiting choose treatment, usually in the form of androgen deprivation therapy, to relieve side effects of locally progressive or metastatic disease. The goal of active surveillance is to allow men to maintain their quality of life when the disease is slow growing or inactive but still allow them to be cured of prostate cancer when the disease appears to become more aggressive or is growing.
A cancer diagnosis is scary for anyone. We know that not all prostate cancers need immediate treatment. This guide presents the American Urological Associations recommendation for prostate screening. Once the concept that a diagnosis of prostate cancer automatically requires treatment is dispelled, the issue of prostate cancer screening in any age group becomes less controversial. Knowledge is power. Talk to your health care provider.
Reviewed: January 2011
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