Biomarkers Personalize PSA Screening

Early diagnosis of prostate cancer (PCa) is marred by a lack of consensus on the best screening strategy. Prostate specific antigen (PSA) had been in widespread use for routine PCa screening, until the U.S. Preventive Services Task Force (USPSTF) recommended against routine PSA screening in 2012. The USPSTF recommendation has cut screening rates, experts say, but its recommendation is not universally accepted and screening recommendations vary substantially among major medical societies in the United States.

A benefit of PSA screening is a reduction in prostate-specific mortality. According to a review published March 30 in the New England Journal of Medicine (NEJM) such mortality is estimated based on a “reasonable summary of the evidence” to be approximately one prostate cancer death averted per 1,000 men screened several times each and followed for 10 to 15 years. Yet, common harms associated with PSA-based diagnosis and the treatment of PCa include: anxiety, urinary incontinence, and erectile dysfunction.

Benefits of early detection are thought to be far off, while harms occur nearly immediately with biopsy, radical prostatectomy, or radiation therapy. The main problem with PSA testing is its lack of specificity, which has been shown to lead to unnecessary, and often repeat biopsies and the overdiagnosis and overtreatment of nonaggressive disease.

“That there is still no clarity about the usefulness and desirability of routine PSA-based screening after 25 years and two large trials suggests that its net benefit is unlikely to be more than marginal, whereas the harms are proven and substantial,” write the authors led by Paul F. Pinsky, Ph.D., from the National Institutes of Health in Bethesda, Md., in the NEJM. “Under the ‘first do no harm’ principle, it seems reasonable to forgo mass screening as a public health policy at this point but to continue to perform research on how to reduce the harms of PSA screening.”

Some screening strategies suggested by Pinsky, include less frequently screening intervals and discontinuing screening for men with very low PSA values. Additionally, though, there is great interest in identifying new biomarkers for diagnosing, staging, and risk-stratifying PCa to inform treatment decisions.

New markers would ideally be collected noninvasively; low enough in processing costs that they could be implemented in widespread screening programs; and differentiate clinically significant cancer from nonaggressive disease.

“Although many studies have shown that novel biomarkers outperform PSA, they are not yet part of daily clinical practice and guidelines,” writes co-author R.J. Hendriks, from Radboud University Medical Center in the Netherlands, in a review published in the March issue of Prostate Cancer and Prostatic Diseases. “We would recommend that before using new biomarkers as tools for risk stratification, biopsy decisions, and treatment selection in patients with PCa, the biomarkers should be validated and prospectively compared with each other. … Longitudinal studies are required following men from initial investigation through to diagnosis and treatment of PCa to determine clinical effectiveness and cost-effectiveness to guide doctor and patient in decision-making regarding PCa diagnostics and treatment selection.”

For further discussion of biomarkers and PSA diagnosis, see the “Special Focus: New Biomarkers May Enable Personalized Prostate Cancer Screening,” in the April issue of DTET.