In the JournalsPerspective

Single prostate cancer screening test offers no benefit

Men who underwent a single PSA testing for prostate cancer screening had mortality rates that closely aligned with those patients who did not get screened at all, according to findings recently published in JAMA.

“Although there is fair-quality evidence that screening by PSA testing reduces prostate cancer deaths, debate continues about the trade-off between the mortality benefit and risks of harm from overdetection and overtreatment,” Richard M. Martin, PhD, of the department of population health sciences at the University of Bristol in England, and colleagues wrote.

Researchers randomly grouped patients recruited between 2001 and 2009 (mean age, 59 years) to either receive a single PSA test or forgo screening. Patients were followed for a median of 10 years.

Martin and colleagues found that after follow-up, 549 of the 189,386 patients in the intervention group (0.30 per 1,000 person-years) died of prostate cancer in this group vs. 647 of the 219,439 patients in the control group (0.31 per 1,000 person-years; rate ratio [RR] = 0.96; 95% CI, 0.85–1.08). A review of all patients’ all-cause mortality showed there were 25,459 deaths among those who received screening, compared with 28,306 deaths among those who did not (RR = 0.99; 95% CI, 0.94–1.03).

Men who underwent a single PSA testing for prostate cancer screening had mortality rates that closely aligned with those patients who did not get screened at all.
Photo credit: Shutterstock

In addition, the number of patients diagnosed with prostate cancer was higher in the intervention group (n = 8,054) vs. those in the control group (n = 7,853; RR = 1.19; 95% CI, 1.14–1.25). Also, of the 64,436 patients in the intervention group who had a positive PSA test result, 6,857 had a PSA level from 3 ng/mL to 19.9 ng/mL and of those, 5,850 underwent biopsy.

“This trial provides new evidence that complements published trials ... [however], extended follow-up of the ... trial is crucial to ascertain whether the evidence of increased detection from the screening intervention coupled with treatment-related effects on the occurrence of metastases translate into longer-term survival benefits,” Martin and colleagues wrote.

Such longer-term follow-up is in process, but the current findings “do not support” single PSA testing for population-based screening, researchers added.

In a related editorial, Michael J. Barry MD, of the division of general medicine at Massachusetts General Hospital, wrote that there are many “remarkable strengths” to Martin and colleagues’ trial, and agreed that their findings “do not provide compelling support for PSA screening.”

He offered some suggestions to the prostate cancer screening process that could provide better emotional, medical and financial benefits.

“Efforts to uncouple the risk of overtreatment from the higher risk of diagnosis may help mitigate the harms of PSA screening for men who decide to be screened. Active surveillance programs appear to be helpful, yet the concern about allowing even a few prostate cancers to escape from possible cure during surveillance may be leading to more and more intensive surveillance, including frequent biopsies and now, magnetic resonance imaging scans. How ‘active’ active surveillance needs to be and which men are candidates requires further research,” he wrote.

“More selective treatment, including avoiding overtreatment of men with low-risk cancer cases but also avoiding undertreatment of men with high-risk cancer cases, combined with offering screening to men aged 55 to 69 years ... even has the potential to make PSA screening cost-effective,” Barry added. – by Janel Miller

Disclosure: Barry reports receiving a salary as chief science officer for Healthwise and receiving grants from that organization that were awarded to Massachusetts General Hospital. He is also a member of the U.S. Preventive Services Task Force, but says his views are not necessarily those of the USPSTF. No other relevant financial disclosures were reported.

Men who underwent a single PSA testing for prostate cancer screening had mortality rates that closely aligned with those patients who did not get screened at all, according to findings recently published in JAMA.

“Although there is fair-quality evidence that screening by PSA testing reduces prostate cancer deaths, debate continues about the trade-off between the mortality benefit and risks of harm from overdetection and overtreatment,” Richard M. Martin, PhD, of the department of population health sciences at the University of Bristol in England, and colleagues wrote.

Researchers randomly grouped patients recruited between 2001 and 2009 (mean age, 59 years) to either receive a single PSA test or forgo screening. Patients were followed for a median of 10 years.

Martin and colleagues found that after follow-up, 549 of the 189,386 patients in the intervention group (0.30 per 1,000 person-years) died of prostate cancer in this group vs. 647 of the 219,439 patients in the control group (0.31 per 1,000 person-years; rate ratio [RR] = 0.96; 95% CI, 0.85–1.08). A review of all patients’ all-cause mortality showed there were 25,459 deaths among those who received screening, compared with 28,306 deaths among those who did not (RR = 0.99; 95% CI, 0.94–1.03).

Men who underwent a single PSA testing for prostate cancer screening had mortality rates that closely aligned with those patients who did not get screened at all.
Photo credit: Shutterstock

In addition, the number of patients diagnosed with prostate cancer was higher in the intervention group (n = 8,054) vs. those in the control group (n = 7,853; RR = 1.19; 95% CI, 1.14–1.25). Also, of the 64,436 patients in the intervention group who had a positive PSA test result, 6,857 had a PSA level from 3 ng/mL to 19.9 ng/mL and of those, 5,850 underwent biopsy.

“This trial provides new evidence that complements published trials ... [however], extended follow-up of the ... trial is crucial to ascertain whether the evidence of increased detection from the screening intervention coupled with treatment-related effects on the occurrence of metastases translate into longer-term survival benefits,” Martin and colleagues wrote.

Such longer-term follow-up is in process, but the current findings “do not support” single PSA testing for population-based screening, researchers added.

In a related editorial, Michael J. Barry MD, of the division of general medicine at Massachusetts General Hospital, wrote that there are many “remarkable strengths” to Martin and colleagues’ trial, and agreed that their findings “do not provide compelling support for PSA screening.”

He offered some suggestions to the prostate cancer screening process that could provide better emotional, medical and financial benefits.

“Efforts to uncouple the risk of overtreatment from the higher risk of diagnosis may help mitigate the harms of PSA screening for men who decide to be screened. Active surveillance programs appear to be helpful, yet the concern about allowing even a few prostate cancers to escape from possible cure during surveillance may be leading to more and more intensive surveillance, including frequent biopsies and now, magnetic resonance imaging scans. How ‘active’ active surveillance needs to be and which men are candidates requires further research,” he wrote.

“More selective treatment, including avoiding overtreatment of men with low-risk cancer cases but also avoiding undertreatment of men with high-risk cancer cases, combined with offering screening to men aged 55 to 69 years ... even has the potential to make PSA screening cost-effective,” Barry added. – by Janel Miller

Disclosure: Barry reports receiving a salary as chief science officer for Healthwise and receiving grants from that organization that were awarded to Massachusetts General Hospital. He is also a member of the U.S. Preventive Services Task Force, but says his views are not necessarily those of the USPSTF. No other relevant financial disclosures were reported.

    Perspective
    Karen Knudsen

    Karen E. Knudsen

    Uncertainties surrounding the overall impact of PSA screening in men have yet to be definitively resolved, with clinical investigations leading to differing guideline recommendations. In the United States, the U.S. Preventative Services Task Force initially recommended in 2012 against routine PSA screening for men of any age, in contrast to recommendations from the American Cancer Society (ACS) and the American Urologic Association (AUA), who both favored a supported decision-making strategy. After the advantage of longer-term follow-up studies in both the U.S. and Europe, and concerns raised about the importance of screening to prevent development of metastatic disease, the USPTSF suggested updated screening recommendations in 2017. Current “grade C” draft recommendations for men aged 55 to 69 years encourage an individualized approach, wherein patient-physician discussions regarding harms and benefits are considered. 

    Recent findings from Martin and colleagues compared men in the U.K. aged 50 to 69 years undergoing a single PSA screen across 573 primary care practices vs. men not undergoing a PSA screening. The study randomized patients between 2001 and 2009, and followed outcome until March 31, 2016. Perhaps not surprisingly, cancer was detected more frequently in the PSA screened group (4.3%) vs. the control group (3.6%), yet over the 10-year period of follow-up, there was no significant different in prostate cancer mortality. These data are important additions to previous studies assessing the impact of PSA testing on cancer specific survival, and indicate that a low-intervention PSA screening may not alter 10-year outcomes. However, care should be exercised in interpretation. The study limited testing to a single PSA screening, and the impact of serial testing in this group of men is not known. Furthermore, longer term follow-up is likely needed to fully assess the impact of PSA screening on prostate cancer mortality. In the U.K., lead time for development of prostate cancer is approximately 12 years. Finally, it is notable that 647 men in the control group and 549 men in the PSA-screened group died of prostate cancer, indicating that a significant subset of lethal prostate cancers were missed even in the screened population. On balance, these findings fail to support single PSA testing for population-based screening, but require further consideration to assess the overall impact of PSA testing in the group aged 50 to 69 years.

    Less clear is how these findings relate to diverse populations with increased risk.  Both the USPTF and AUA agree that men at increased risk, including African American men and men with a family history, should discuss the risk and benefit of testing. Evidence now shows that up to 15% of all prostate cancers are associated with inherited risk, thus heightening the importance of performing a rigorous family history intake and when appropriate, referring for genetic evaluation. Suggested guidelines for genetic referral include men with a family history of cancers (including prostate, breast, ovarian, colon, uterine and pancreatic cancer), and men with a first-degree relative who died of prostate cancer before age 60. Understanding how genetic risk impacts the utility of PSA testing, including low-intensity screening, will likely be of benefit. With the rapid pace of discovery, including advances in imaging and molecular testing, it is anticipated that PSA testing will be complemented by additional strategies for accurate early detection and identification of lethal disease.

    • Karen E. Knudsen, PhD
    • Director, Sidney Kimmel Cancer Center at Thomas Jefferson University and Jefferson Health
      Professor, Cancer Biology, Urology, Radiation Oncology & Medical Oncology at Sidney Kimmel Medical College at Thomas Jefferson University