If you and your physician agree to use screening tests to look for prostate cancer, decisions on whether to perform a prostate biopsy may be based on the total level of prostate specific antigen (PSA) and the rate at which it increases, termed PSA velocity. Most doctors use a level of PSA of greater than 4.0 ng/mL to recommend doing a prostate biopsy, but some guidelines suggest that a biopsy be considered if PSA velocity (calculated using at least 3 PSA measurements over a period of 18-24 months) is more than 0.35 ng/mL per year, even if the total PSA is low.
A recent analysis of the data from a large study suggests that PSA velocity adds little additional information to total PSA and questions its importance. The study, published in the March 16, 2011 issue of the Journal of the National Cancer Institute, concludes that many unnecessary prostate biopsies occur because this calculation is used in decision making. "We found no evidence to support the recommendations that men with high PSA velocity should be biopsied in the absence of other indications; this measure should not be included in practice guidelines," the researchers conclude.
In plain terms, the lead author of the study, Andrew Vickers, PhD, explains: "If a man's PSA has risen rapidly in recent years, there is no cause for concern if his total PSA level is still low and his clinical exam is normal."
Will the Findings Tighten Future Guidelines?
Guidelines from the American Urological Association and National Comprehensive Cancer Network advise that when the PSA level rises rapidly, a biopsy should be considered. The U.S. Preventive Services Task Force and American Cancer Society are among the groups that do not endorse PSAV for screening.
The PSA test and digital rectal exam are the primary tools used to try to find prostate cancer early. Age, family history of prostate cancer, and history of prostate biopsy also matter. Derivatives of the PSA test, such as PSAV, are sometimes considered. PSAV helps show how rapidly PSA levels have gone up over time. However, factors other than cancer can also cause PSA to go up over time, such as benign prostatic hyperplasia (BPH) and infection or inflammation of the prostate (prostatitis).
The study assessed PSAV's clinical value for early detection of prostate cancer. It looked at data from the 7-year-long Prostate Cancer Prevention Trial, which compared the ability of a prevention drug with no treatment on development of prostate cancer in men 55 or older; to prove whether it worked, all men who were not diagnosed with prostate cancer during the 7 years were asked to undergo a prostate biopsy at the end of the study. Vickers and colleagues evaluated 5,519 men who had received no treatment, had yearly PSA tests, and had a biopsy at the end of the study. The authors found the following results:
- Prostate cancer was found in 22% of the men undergoing biopsy at the end of the study. Because some prostate cancers grow most slowly than others, the study also looked at several features that have been used to predict likelihood that cancer would cause problems in the future, including age, the pathologic features of the cancer, ethnic background, total PSA, and PSA velocity. Cancers that were likely to cause problems were termed aggressive cancers.
- If PSA velocity was looked at alone, more men (nearly 1 in 7) would have had a biopsy performed, which was much higher than using total PSA over 4.0 ng/mL (1 in 20). This would detect more prostate cancers, but for every cancer that was found, 4 men who didn't have cancer would have also had biopsies.
- While PSA velocity picked up more cancers, it reflected the same proportion of aggressive cancers detected with total PSA.
- Using a lower cutoff for PSA (2.5 ng/mL or higher) to decide to do a biopsy would have detected slightly more cancers than PSA velocity, with a similar number of men without cancer undergoing biopsy.
Reducing the Harm
Discomfort is not the only side effect a man may suffer from a biopsy. The National Cancer Institute notes these other complications of a biopsy: blood in the semen or urine, infection in the urinary tract, transient fever, pain and even, rarely, sepsis. Also, a man who has a biopsy is more likely to visit a urologist, get follow-up PSA tests within a year, and even have another biopsy. These add to the financial and psychological costs and introduce opportunities for problems to develop.
An editorial by Siu-Long Yao, MD, and Grace L. Lu-Yao, PhD, gave this summary of the study: "Because PSA velocity did not enhance outcomes or improve the detection of more aggressive cancers, the authors conclude that PSA velocity did not add predictive accuracy beyond PSA values alone and noted that one would be better off lowering the threshold for biopsy rather than adding PSA velocity as a criterion for biopsy."
It is too early to know how any guidelines will change in response to this research or to the recommendation to leave PSAV out of the screening toolbox. Patients should discuss with their doctors the pros and cons of available tests when deciding to screen for prostate cancer.
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Bankhead C (24 Feb 2011). Study knocks diagnostic value of PSA velocity. MedPage Today. Available online through http://www.medpagetoday.com. Accessed April 2011.
Memorial Sloan-Kettering Cancer Center (24 Feb 2011). Change in PSA level does not predict prostate cancer (press release). Available online at http://www.mskcc.org/mskcc/html/1095.cfm through http://www.mskcc.org. Accessed 13 Apr 2011.
National Cancer Institute. PDQ Prostate Cancer Screening: evidence of harms. Bethesda, MD: National Cancer Institute. (Last modified 3 Dec 2010.) Available online at http://cancer.gov/cancertopics/pdq/screening/prostate/HealthProfessional through http://cancer.gov. Accessed 14 Apr 2011.
Thompson IM. The influence of finasteride on the development of prostate Cancer. New Engl J Med2003;349(3): 215-224.
Vickers AJ, et al (16 Mar 2011). An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection. J Natl Cancer Inst 103(6):462-468.
US Preventive Services Task Force (5 Aug 2008). Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. Ann Intern Med 149:(3):185-191. Available online at http://www.uspreventiveservicestaskforce.org/uspstf/uspsprca.htm through http://www.uspreventiveservicestaskforce.org. Accessed 12 Apr 2011.
Yao SL and Lu-Yao GL (16 Mar 2011). The science and art of prostate cancer screening (editorial) J Natl Cancer Inst 2011;doi:10.1093/jnci/djr047.