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PSA: The Little Kallikrein that “COULD” and “SHOULD”

The U.S. Preventative Services Task Force (and later the Canadian Task Force on Preventive Health Care) recommended against using the PSA test to screen for prostate cancer, since it could result in "overdiagnosis" and “overtreatment” because “most prostate cancer is asymptomatic for life.”1 However, prostate cancer remains the number-one diagnosed cancer in men in North America and the second- or third-most-common "killing cancer"
in North American men.

Dr. T. Ming Chu and colleagues from Roswell Park Cancer Institute in Buffalo, New York were the first group to really purify and characterize PSA and show that it was virtually “prostate specific,” as they described in their 1979 article.2 In 1991, Catalona published the first results of a study showing that PSA was the most accurate method for detecting prostate cancer and suggested that it should be used as a first-line screening test for prostate cancer.3 However in 2011, Gomella et al noted that there was conflicting evidence about using PSA tests to screen for prostate cancer and suggested that physicians should discuss this with their patients.4

Since the early 90s, after the widespread use of PSA tests to screen for prostate cancer, we have seen a drop in deaths due to prostate cancer. Prostate-cancer screening trials such as the Göteborg trial have demonstrated significant survival benefits with a relatively small "number needed to screen."5

However, some researchers have suggested that the incidence of significant morbidity associated with trans-rectal ultrasound (TRUS)-guided biopsies can be as high as 5%.6 Because of this, we have almost reversed our approach and are looking for an excuse not to biopsy patients, for fear of causing morbidity and/or detecting an “insignificant” cancer.

Today, abnormal values for total PSA, age-related PSA, free-to-total PSA ratio, and PSA density are still the primary drivers of first-time prostate biopsies. If a patient is diagnosed with cancer, we use PSA values as one of the significant factors to insert into Partin tables to predict risk of cancer spread.

After primary prostate-cancer treatment, we again use PSA as the marker to indicate success or failure. With post- secondary therapy with hormonal manipulation, rising PSA levels suggest the development of castrate-resistant prostate cancer. We use the PSA doubling time to determine whether to escalate to the next treatment. We then look to PSA to signal failure of the newer “super hormonal manipulators” such as abiraterone and enzalutamide.

New biomarkers have been promoted in the pre-biopsy space to determine the risk of finding significant cancer. Some clinicians have advocated the use of the 4Kscore test, which uses 4 kallikreins—total PSA, free PSA, intact PSA and human kallikrein 2 (hK2).7

Thirty-six years after Chu and colleagues proved the significance of PSA as a marker, it is still the kallikrein marker that could, and now more than ever should, be used to prevent unnecessary biopsies while helping us detect clinically significant prostate cancers.

Jack Barkin, MD Executive Deputy Editor University of Toronto Toronto, Ontario, Canada

1. Moyer VA. Screening for Prostate Cancer: US Preventative Services Task Force Recommendation Statement: Ann Intern Med 2012;157(2): 120-134.

2. Wang MC, Valenzuela LA, Murphy GP, CHU TM. Purification of a human prostate specific antigen. Invest Urol 1979;17(2):159-163.

3. Catalona WJ, Smith DS, Ratliff TL et al. Measurement of prostatic-specific antigen in serum as a screening test for prostate cancer. N Engl J Med


4. Gomella LG, Liu XS, Trabulsi EJ et al. Screening for prostate cancer : the current evidence and guidelines controversy. Can J Urol 2011;18(5):


5. Hugosson J, Carlsson S, Aus G et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol

2010;11(8) :725-732.

6. Nam RK Saskin R, Lee Y et al. Increasing hospital admission rates for urologic complications after TRUS guided prostate biopsy. J Urol 2013;

189(1 Suppl):S12-S18.

7. Parekh DJ, Punnen S Sjoberg JJ et al. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with

high-grade prostate cancer. Eur Urol 2014. Epub ahead of print.

© The Canadian Journal of Urology™; 22(3); June 2015