Meta-analysis consolidates evidence against PSA-based screening
medwireNews: Prostate-specific antigen (PSA)-based screening may lead to a modest reduction in prostate cancer-specific mortality but has no effect on overall survival, say the authors of a meta-analysis published in The BMJ.
“Clinicians and patients considering PSA based screening need to weigh these benefits against the potential short and long term harms of screening, including complications from biopsies and subsequent treatment, as well as the risk of overdiagnosis and overtreatment,” they write.
Medicine Matters editorial board member Axel Merseburger (University Hospital Schleswig-Holstein, Lübeck, Germany) agreed with the authors’ conclusions and noted that this meta-analysis could signal the end of the debate on PSA-based screening.
He anticipates that advances in magnetic resonance imaging (MRI)-based screening and the use of novel age-adjusted screening models, such as that being investigated in the PROBASE trial, “will change screening in the future.”
The meta-analysis comprised data on 721,718 men enrolled in five randomized controlled trials – including the CAP trial published earlier this year – that compared PSA-based screening with usual care in men who did not have prostate cancer.
Across all trials, PSA-based screening did not appear to be associated with a significant reduction in all-cause or disease-specific mortality, with corresponding pooled incidence rate ratios (IRRs) of 0.99 and 0.96 relative to usual care. This equates to one less death from any cause and zero fewer prostate-cancer specific deaths for every 1000 individuals screened, say the study authors.
They note, however, that due to the considerable risk for bias in the majority of the included trials, the quality of evidence was low to moderate for the various analyses. But in a sensitivity analysis of the one trial considered to have the lowest risk for bias, the findings for all-cause mortality were similar to those of the main analysis, with an IRR of 1.00.
By contrast, the incidence of prostate cancer-specific mortality appeared to be lower with screening than with usual care, at an IRR of 0.79. In absolute terms, this translated into one less death for every 1000 men who underwent screening.
Additionally, in the main analysis, PSA-based screening was associated with an increased detection of early-stage prostate cancer (risk ratio=1.39) and a “modestly” reduced incidence of advanced prostate cancer (risk ratio=0.85), report Philipp Dahm – from the University of Minnesota in Minneapolis, USA – and team.
Although the data on screening-related harms were limited, they estimate that for every 1000 individuals screened, approximately 25 more men would report erectile dysfunction relative to no screening, while an additional three men would develop urinary incontinence and one more individual would be hospitalized for sepsis.
The authors of a related editorial say that more precise characterization of an individual’s risk of developing nonaggressive or aggressive prostate cancer, “alongside less invasive methods of detecting potentially life-shortening disease are key to improving outcome for this most common of solid cancers.”
Martin Rolan (University of Cambridge, UK) and colleagues conclude: “In the meantime, conversations with patients requesting a PSA test should explore their reasons for requesting a test and include evidence based discussions about possible harms and benefits of PSA testing—informed by the patient’s ethnicity and family history—and about recent advances in the use of [multi-parametric]-MRI and active surveillance, which have the potential to reduce the harms of testing.”
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