But analysis doesn’t address harms from screening and subsequent treatment

by Molly Walker, Staff Writer, MedPage Today September 04, 2017

Prostate cancer screening resulted in a lower risk of prostate cancer death for older men, according to pooled data from two pivotal trials that shaped recent recommendations on PSA testing.
Compared with those who received no screening, estimated risk of prostate cancer death was cut by 25% to 31% among men in the intervention groups of the European Randomized Study of Screening for Prostate Cancer (ERSPC) and by 27% to 32% in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), reported Alex Tsodikov, PhD, of the University of Michigan, and colleagues.
Moreover, there was a 7% to 9% reduction in the risk of prostate cancer death per year of mean lead times, or the average time by which diagnosis is advanced by screening versus without screening.
These extended analyses were published in the Annals of Internal Medicine.
Notably, they did not address potential harms from screening and follow-up procedures. Nevertheless, the analyses may add more fuel to the fire in the ever-evolving debate about the merits of prostate cancer screening. While the U.S. Preventive Services Task Force recommended against screening in 2012, a draft recommendation statement from April 2017 supported “discussion-backed” decisions for men about screening — upgrading those recommendations to a grade of C.
Otis Brawley, MD, chief medical officer of the American Cancer Society, who was not involved in the research, told MedPage Today that this data “truly supports” what the American Cancer Society has been saying since 2010 — that the decision to screen should be made after an informed discussion between doctor and patient.
“Within the physician/patient relationship — not in a mall, at the state fair, or at the 1996 Republican National Convention — there should be a discussion about the potential benefits and harms of prostate cancer screening,” he said.
But these recommendations “relied heavily” on results from the ESPRC and the PLCO, said the authors — studies with conflicting results. The ERSPC found a 21% reduction in mortality rates, but the PLCO found “no difference” in mortality.
However, Tsodikov and colleagues argued that differences in the trial results were “complicated by differences in their implementation.” The PLCO was conducted in the U.S., where prostate cancer incidence is higher than in Europe, in a U.S. practice based setting, where the control group likely had more frequent screening than in the ERSPC control group, they said. In addition, the PLCO compared “organized screening versus opportunistic screening” as opposed to screening versus no screening, and age ranges were slightly different (PLCO examined men ages 55 to 69, while PLCO examined men ages 55 to 74 years). Other methodological differences included:
• Shorter screening interval (annual versus every 2 to 4 years)
• Higher PSA threshold for biopsy referral (4.0 μg/L versus 3.0 μg/L)
• Stopped regular screening after six rounds
Using individual records from both trials, researchers performed extended analyses to account for “screening intensity” by estimating mean lead times. While they found no difference on the effects of screening on mortality between trials (P=0.37-0.47 for interaction), they did find that a longer mean lead time was linked to a significantly lower risk of prostate cancer deaths, after adjusting for baseline risks between trial setting and participant age.
Brawley did note that mean lead time is “not a standard measure we use in epidemiology,” characterizing it as “somewhat controversial.”
An accompanying editorial by Andrew J. Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City, compared the ERSPC and the PLCO trials to “a trial of 1,000 mg of aspirin versus placebo with a trial of 1,000 mg versus 900 mg of aspirin.”
He added that he hoped this research would help to “refocus” the debate about PSA testing. Vickers called for “commonsense strategies,” such as shared decision making, to stop screening men over 70 and that biopsy should only be done in men “who screen positive and are at risk for aggressive disease.”
“PSA-based screening does reduce prostate cancer mortality, but whether this benefit outweighs the harms of overdiagnosis and overtreatment depends on how screening is implemented,” Vickers wrote.
Brawley, who characterized the editorial as “a must-read for primary care physicians,” added that more and more men who are diagnosed with prostate cancer through screening are receiving observation as a form of therapy, rather than aggressive radiation.
“The risk/benefit ratio is changing because nowadays, nearly half of all men diagnosed through screening are being watched, whereas 10 years ago, almost no one was being watched,” he noted.

This study was supported in part by grants from the National Cancer Institute.
Tsodikov disclosed no conflicts of interest.
Other co-authors disclosed support from the Prostate Cancer Research Foundation, the European Association of Urology, EPID Research, MSD, Myriad, Astellas, Janssen, Fondo de Investigacio´n Sanitaria, GRAIL and Seno.
Vickers disclosed grant support from the Sidney Kimmel Center for Prostate and Urologic Cancers, the National Cancer Institute, and the NIH.
• Primary Source
Annals of Internal Medicine
Source Reference: Tsodikov A, et al “Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials” Ann Intern Med 2017; DOI: 10.7326/M16-2586.
• Secondary Source
Annals of Internal Medicine
Source Reference: Vickers AJ “Prostate cancer screening: Time to question how to optimize the ratio of benefits and harms” Ann Intern Med 2017; DOI: 10.7326/M17-2012.