Prostate Specific Antigen (cont.)
Kevin C. Zorn, MD, FRCSC, FACS
Dr. Kevin Zorn is a dual-board-certified (US and Canada), minimally-invasive uro-oncology, fellowship trained urologist at the University of Chicago. His main focus of clinical and scientific interest is in the surgical treatment of renal and prostate cancer. He is also an expert in performing surgery with the DaVinci Surgical Robotic System to manage localized prostate cancer and small renal masses. Dr. Zorn studied medicine and urology at McGill University in MontrĂ©al.
Melissa Conrad Stöppler, MD
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
In this Article
- Prostate specific antigen (PSA) facts
- What is prostate specific antigen?
- How is PSA measured?
- What causes PSA elevation in the blood?
- What are normal results for the PSA test?
- What are age-specific reference ranges for serum PSA?
- How is PSA used for early detection prostate cancer?
- What is the free PSA test?
- What is free/total PSA ratio?
- What is PSA velocity and PSA doubling time?
- How is PSA testing used for pretreatment staging of prostate cancer?
- How is PSA testing used in the management of prostate cancer posttreatment?
- What are the limitations of the PSA test?
- What is digital rectal examination (DRE)?
- What is the PSA screening controversy?
- How should the PSA test be used for the early detection of prostate cancer?
- What is PCA3?
What are the limitations of the PSA test?
The level of PSA is a continuous parameter; the higher the value, the higher the probability of having prostate cancer. On the other hand, men may have prostate cancer despite low levels of PSA. In a recent U.S. prevention study, 6.6% of the men whose PSA level was less than 0.5 ng/mL had prostate cancer. This is why there is no universally accepted cutoff at which we can be sure that there is no prostate cancer. Coupled with the lack of an accurate molecular marker to detect prostate cancer, the other controversy with PSA screening is the fact that not all men with prostate cancer will ever die from the disease (See: What is the PSA screening controversy?).
For these reasons outlined above, it is important to not solely rely on blood PSA testing. The most useful additional test is a physical prostate examination by a doctor known as the digital rectal exam (DRE). Evidence from research studies suggests that the combination of both PSA and DRE improves the overall rate of prostate cancer detection. For that reason, men who would like to be screened for prostate cancer should have both a prostate specific antigen (PSA) test and a digital rectal examination (DRE).
What is digital rectal examination (DRE)?
Most prostate cancers are located in the peripheral zone of the prostate and may be detected by DRE. During this examination a doctor inserts a finger into the rectum to feel the prostate for lumps, size, shape, tenderness, and hardness. A suspect DRE is an absolute indication for prostate biopsy. In about 18% of patients with abnormal DRE, prostate cancer will be detected regardless of the PSA level.
What is the PSA screening controversy?
The goal of measuring PSA in men with no symptoms of cancer as a screening test for prostate cancer is to reduce the mortality caused by this cancer. However the usage of PSA as a screening tool for early detection of prostate cancer is subject to controversies over its ability to save lives.
Widespread use of PSA screening came into practice particularly in North America driven by the assumption that detecting prostate cancers earlier will allow for earlier treatment and thereby decrease mortality caused by this disease.
A substantial number of the cancers detected by PSA screening are low stage, and these patients will likely never die from this disease. PSA screening, due to its low specificity, does not allow differentiating between lethal and nonlethal types of cancers. Hence PSA systematic screening is inevitably associated with overdiagnosis and potentially overtreatment. Therefore, not only do these patients not benefit from early detection but they also carry the burden of a cancer diagnosis. In addition, a subset of these patients may suffer the side effects of an unnecessary treatment.
Despite the inconvenience caused by overdiagnosis and overtreatment, one may argue that PSA screening can still be considered successful if overall, it improves disease-specific mortality in the population as a whole. Unfortunately, the conflicting results obtained from several randomized clinical trials specifically designed to evaluate the impact of PSA testing on prostate cancer mortality have not clarified the issue.
One large European trial (ERSPC) found that PSA screening significantly reduces the mortality (death rate) of prostate cancer but is also associated with a high risk of overdiagnosis. The cumulative incidence of prostate cancer was 8.2% in the PSA screening group and 4.8% in the control group. Patients in the screening group were 20% less likely to die from prostate cancer compared with the control group. The absolute risk difference between the two groups was 0.71 deaths per 1,000 men. This means that to prevent one death from prostate cancer, 1,410 men would need to be screened with PSA testing and 48 additional cases of prostate cancer would need to be treated.
Another trial (PLCO) conducted in the United States recently concluded that there is no evidence of an improvement in death rate from prostate cancer with annual PSA screening compared with usual medical care. After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control groups were 3.7 and 3.4 deaths per 10,000 person-years, respectively, meaning that there was significant difference between the two groups.
Based on the results of the PLCO trial, the U.S. Preventive Service Task Force (USPSTF) advised against PSA screening in their draft recommendation issued in 2011. Nevertheless, many experts continue to believe that not using PSA screening would result in the deaths of many men with curable prostate cancer.
Accordingly, although the effect of PSA screening on overdiagnosis and overtreatment of patients whose prostate cancer might not have resulted in death is of concern, early detection as opportunistic screening should still be offered. More than the overdiagnosis, the real challenge is to avoid overtreatment. Many patients with small, low-grade cancers may be candidates for active surveillance without treatment. This is why it is very important that men have an open and informed discussion with their doctor on the risks and benefits of prostate cancer screening before biopsy. In addition, the option of active surveillance instead of immediate treatment should always be discussed in case of newly diagnosed prostate cancer, if appropriate.
Despite the controversy of several recent publications and task force recommendations, the American Urological Association (AUA) still recommends the use of PSA for early prostate cancer detection. Early detection and risk assessment should be offered to men 40 years of age or older who wish to be screened. The fundamental principle of the AUA position is that knowing a man's baseline PSA values in his 40s to compare with future PSA tests could help identify those men with life-threatening prostate cancer at a time when there are many treatment options and cure is possible.
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