A large 15-year multi-centre US study shows little difference in mortality between men screened annually for prostate cancer and the control group, some of whom chose to be screened occasionally.
Starting in 1993 and ending in 2001, ten academic medical centres in the US screened 76,685 men and 78,216 women for prostate, lung, colorectal and ovarian cancers. The question was whether yearly screening could catch cancers early and thus decrease mortality from these diseases. Fifteen-year follow-up results focusing on prostate cancer were recently published, and show little difference in mortality between men screened annually and the control group, some of whom chose to be screened occasionally. According to researchers, the results don't necessarily negate the value of prostate cancer screening, but imply that within the data of this massive trial are clues that inform personalised decisions for subsets of this prostate cancer population.
"What we can see from these results is that most men diagnosed with prostate cancer will not die from their disease. In 15 years, people on the study died from lots of other things. However, we can also see that now we need to focus on discovering the men that will," says Dr E David Crawford, investigator at the University of Colorado Cancer Centre and study co-author.
Specifically, in the intervention arm that received annual prostate cancer screening, 255 men have died of prostate cancer since the start of the trial. In all, 244 men in the control arm, who did not receive annual screening (but may have received self-directed intermittent screening), died of prostate cancer. By comparison, 1,933 and 1,882 men in the experimental and control arms, respectively, died of other cancers. Slightly more in each group died of heart-related conditions.
According to Crawford, these data imply that some men need not be screened for prostate cancer. "For example, we have since shown that men with PSA lower than one have only about a 0.5% chance of being diagnosed with prostate cancer within 10 years," Crawford says. Administering a PSA test first and then not screening men with PSA less than one would save billions of dollars in healthcare costs every year.
However, in addition to discovering no decreased mortality with yearly prostate cancer screening compared with intermittent screening, Crawford suggests that these results could be used to discover men who do, in fact, benefit from careful monitoring.
"I treated a guy who'd been diagnosed in his 40s," says Crawford. "We did surgery, but then a year later he was diagnosed with melanoma. It turned out that at the same time, his sister was diagnosed with triple-negative breast cancer and died within the year.
Being diagnosed with prostate cancer in your 40s is a red flag that there might be a germline mutation to blame, predisposing these men and maybe family members who share the mutation to more, and more aggressive cancers. The PLCO shows that most men don't benefit from screening, but if we could have used the data to spot this guy, maybe we could have even tested his sister as well."
And so the takeaway from this retrospective on a massive study, 15 years after the completion of data gathering, is that despite what many have characterised as failure – after all, yearly screening did not result in overall lives saved – is that inside this data (or in related, follow-up studies) may still exist clues that could stratify prostate cancer risk.
Alongside the risks and costs of over-diagnosis and over-treatment that come with screening the entire population of men for prostate cancer still exists hope that screening only those with higher risk, at the right schedule, could save lives.
Abstract
Background: Two large-scale prostate cancer screening trials using prostate-specific antigen (PSA) have given conflicting results in terms of the efficacy of such screening. One of those trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, previously reported outcomes with 13 years of follow-up. This study presents updated findings from the PLCO trial.
Methods: The PLCO trial randomized subjects from 1993 to 2001 to an intervention or control arm. Intervention-arm men received annual PSA tests for 6 years and digital rectal examinations for 4 years. This study used a linkage with the National Death Index to extend mortality follow-up to a maximum of 19 years after randomization.
Results: Men were randomized to the intervention arm (n = 38,340) or the control arm (n = 38,343). The median follow-up time was 14.8 years (25th/75th, 12.7/16.5 years) in the intervention arm and 14.7 years (25th/75th, 12.6/16.4 years) in the control arm. There were 255 deaths from prostate cancer in the intervention arm and 244 deaths from prostate cancer in the control arm; this meant a rate ratio (RR) of 1.04 (95% confidence interval [CI], 0.87-1.24). The RR for all-cause mortality was 0.977 (95% CI, 0.950-1.004). It was estimated that 86% of the men in the control arm and 99% of the men in the intervention arm received any PSA testing during the trial, and the estimated yearly screening-phase PSA testing rates were 46% and 84%, respectively.
Conclusions: Extended follow-up of the PLCO trial over a median of 15 years continues to indicate no reduction in prostate cancer mortality for the intervention arm versus the control arm. Because of the high rate of control-arm PSA testing, this finding can be viewed as showing no benefit of organized screening versus opportunistic screening.
Authors
Paul F Pinsky, Philip C Prorok, Kelly Yu, Barnett S Kramer, Amanda Black, John K Gohagan, E David Crawford, Robert L Grubb, Gerald L Andriole
[link url="https://www.sciencedaily.com/releases/2016/12/161208143508.htm"]University of Colorado Anschutz Medical Campus material[/link]
[link url="http://onlinelibrary.wiley.com/doi/10.1002/cncr.30474/abstract"]Cancer abstract[/link]