Prostate cancer screening. There is no question that screening for prostate cancer has been the subject of much controversy over the last five to ten years. Different professional organizations, including the American Neurological Association, the American Cancer Society and the American Medical Association all have slightly different recommendations regarding prostate cancer screening. And an organization called the US Preventative Task Force has actually put out a guideline that suggests prostate cancer screening may not be appropriate in men at all. Here, we talk about the guidelines from the American Urological Association. There are no set guidelines. What the American Urological Association suggests is that every man should have a discussion with his physician about the following ideas. Number one, to have a yearly digital rectal exam starting at age 50. Number two, to have a PSA blood test every year between the ages of 55 and 69. And number three, if you're an African American or have a positive family history, screening should be discussed with a health care provider starting as early as age 40. The digital rectal exam done yearly starting at age 50, is done by a health care provider who places a finger in the rectum to feel for a lump in the prostate that would indicate the possibility that cancer is growing. This is a painless procedure, slightly uncomfortable, but a very important part of screening for prostate cancer, one that should not be avoided. Prostate Specific Antigen, or PSA, is a blood test that is at the heart of prostate cancer screening. As a blood test, it should be discussed with a health care provider. As a yearly test between the ages of 55 and 69. PSA is a protein produced by cells of the prostate gland. The PSA blood test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are usually reported as nanograms of PSA per milliliter of blood. A normal PSA level is considered to be 4 nanongrams per mil or less. For men in their 50s or younger, a PSA level should be below 2.5 in most cases. Older men often have slightly higher PSA levels than younger men. Screening leads to approximately 1 million biopsies per year in the United States. Most men with an elevated PSA level turn out not to have prostate cancer, because remember, PSA is produced by normal prostate epithelial cells as well as prostate cancer cells. Only about 25% of men who have a prostate biopsy due to an elevated PSA level actually are diagnosed with prostate cancer. So again, why is screening controversial? Well, detecting prostate cancer early may not reduce the chance of dying from prostate cancer. When used in screening, the PSA test can help detect small tumors that do not cause symptoms. Finding a small tumor, however, may not necessarily reduce a man's chance of dying from prostate cancer. Some tumors found through PSA testing grow so slowly that they are unlikely to threaten a man's life. Detecting tumors that are not life threatening is called overdiagnosis, and treating these tumors is called overtreatment. Overtreatment exposes men unnecessarily to the anxiety of a cancer diagnosis and the potential complications of treatment for a prostate cancer that would have never harmed the man in his lifetime. Remember, I told you that 80% of men at the age of 80, an autopsy are found to have evidence of a prostate cancer. Some of those are diagnosed, some of them aren't. Potential side effects of surgery and radiation include urinary incontinence, erectile dysfunction, and problems with the bowel. We'll talk more about this in lecture three. In addition, finding cancer early may not help a man who has a fast growing or aggressive tumor that may have spread to other parts of the body before being detected. So because of these issues, the United States Preventative Services Task Force analyzed the data from multiple trials and estimated that for every 1,000 men ages 55 to 69 who are screened every 1 to 4 years for a decade, only 0 to 1 death from prostate cancer would be avoided. A 100 to 120 men would have a false positive test leading to a biopsy. And a 110 men would be diagnosed with prostate cancer. About 50 of these men would have a complication from treatment, including erectile dysfunction in 29 men and urinary incontinence in 18 men. It should be noted that these data from these trials are controversial. And the task force is constantly reevaluating new data. New guidelines for screening should be coming out in 2017 or 2018. While we wait for new guidelines, many physicians and investigators are trying to improve the current prostate specific antigen blood test. One of these improvements is free versus total PSA. The amount of PSA in the blood that is free, or not bound to other proteins, is divided by the total amount of PSA free plus bound. Some evidence suggests that a lower proportion of free PSA may be associated with more aggressive cancer. So when the total PSA is in the range of 4 to 10 nanograms per mil, a free to total PSA ratio of less than or equal to 0.1 indicates a 49% to 65% risk of prostate cancer depending on the age. A higher free to total PSA ratio of greater than 0.25 indicates a much lower risk in the 9% to 16% range of having prostate cancer. Many physicians use the free versus total PSA number to help them follow men who may be at risk of prostate cancer because their PSA test is elevated. Another example of improving on the PSA blood test are age-specific ranges. Because a mans PSA level tends to increase with age, generally as a result of BPH, it has been suggested that the use of age specific PSA reference ranges may increase the accuracy of PSA tests. However, age-specific reference ranges have not been generally favored because their use may delay the detection of prostate cancer in many men. Two other concepts that have been used to improve PSA screening are PSA velocity and PSA doubling time. PSA velocity is the rate of change in a man's PSA level over time, expressed as ng/mL per year. PSA doubling time is the period of time over which a man's PSA level doubles, for example, from one to two. Some evidence suggests that the rate of increase in a man's PSA level may be helpful in predicting whether he has prostate cancer. It has been suggested that if a PSA rises by more than 0.7 nanograms per male in a year, it is more likely to find prostate cancer on a biopsy. The take home message here is that getting a PSA blood test yearly between the ages of 55 and 69 is probably the most appropriate way to follow and screen for prostate cancer. There are some newer tests that are available to try and improve on PSA blood tests. One is the Prostate Health Index, or PHI. It is blood test that is used to predict the risk of having prostate cancer. It is used instead of the traditional PSA test. The PHI is actually derived from the PSA test because it is a combination of the free PSA, total PSA, as well as a proPSA isoform of free PSA. These three tests are mathematically combined in a formula that results in the Prostate Health Index. The five score appears to be a better predictor of prostate cancer than total PSA test alone or the free PSA test alone. It appears to be a better predictor of prostate cancer risk than the free PSA to total PSA ratio or the free PSA ratio. The Prostate Health Index is becoming more commonly used every day. Another test is called the 4Kscore. The 4Kscore test combines four prostate-specific kallikrein assay results with clinical information in an algorithm that calculates the individual patient's percent risk for developing aggressive prostate cancer or having aggressive prostate cancer. It is a more accurate test to assess a patient's risk for aggressive prostate cancer prior to a prostate biopsy than PSA alone. Men with a slightly elevated PSA can use the 4Kscore test to help decide whether to have a prostate biopsy. The test has been shown to identify the actual risk of aggressive prostate cancer for an individual patient including high-grade prostate cancer and prostate cancer clinical outcomes within 20 years. For example, a man with a PSA of greater than 3 at age 60 has about a 10% chance of having developed metastatic prostate cancer at 20 years. But if the man has a 4kscore done and it has a score greater than 7.5%, then he has an approximate 15% risk of having metastatic prostate cancer at 15 years. If the 4Kscore is less than 7.5%, the risk is approximately 2%. Therefore, the 4Kscore can be used by the clinician and the patient to decide whether he is harboring a aggressive prostate cancer and whether he wants to undergo a biopsy. How well the 4Kscore will be utilized in the coming years is unclear.
