Limit PSA Screening to Men With Symptoms

Neil Osterweil

May 18, 2023

A new strategy proposed by an international team of experts would limit the use of the prostate-specific antigen (PSA) test for screening tor prostate cancer to men who are younger than 70 years and who are at high risk or symptomatic.

This would reduce potential harms from overdiagnosis and overtreatment, the risk for which is high with the on-demand screening that is the current standard of care in most wealthy nations.

In a paper published online on May 17 in the BMJ, the panel recommends instead a comprehensive nationwide program that would base PSA testing on individual patient risk and direct those with abnormal results to a managed system of imaging, targeted biopsy only if indicated, and subsequent active monitoring or treatment for those with more aggressive disease features.

Alternatively, government health programs could actively discourage widespread PSA testing and implement policies that would effectively limit PSA-based screening only to men with urologic symptoms warranting further exploration, say the authors, led by Andrew Vickers, PhD, a research epidemiologist at Memorial Sloan Kettering Cancer Center in New York, New York.

"Although we believe that early detection of prostate cancer should involve shared decision making, the current approach of determining testing by shared decision making has resulted in the worst possible practical outcome of high levels of PSA testing and medical harm, with minimal benefit and inequity," they comment.

"To make better use of PSA testing, policy makers should choose between a comprehensive, risk adapted approach that is specifically designed to reduce overdiagnosis and overtreatment, or restricting PSA testing to people referred to urologists with symptoms. That choice will need to take into account wider patient and public perspective, as well as health economic concerns," they continued.

Inappropriate Testing

Since the US Food and Drug Administration approved the first PSA screen in 1986 as a means for monitoring disease progression in patients being treated for prostate cancer, the test has remained controversial, embraced by some for its presumed ability to spot early prostate cancer but scorned by others for its equivocal results in patients with benign prostate pathology and for its potential to lead to overdiagnosis and overtreatment of low-grade disease in men who would otherwise be likely to die of other causes.

Currently, only Lithuania and Kazakhstan have government-supported population-based screening programs for prostate cancer. In contrast, the United States, United Kingdom, and other high-income countries have opted not to implement nationwide prostate cancer screening but allow so-called "informed choice testing," in which men can receiving PSA screening after discussion with a primary care physician, urologist, or other specialist.

The US Preventive Services Task Force recommends that for men aged 55-69 years, the decision to undergo PSA testing should be an individual one, based on an understanding of the risks and benefits. For men aged 70 or older, the task force flatly states, "Do not screen for prostate cancer."

But as Vickers and colleagues note, "[h]igh income countries that have made PSA testing available to men who request it after shared decision making with their physician now have a high prevalence of PSA testing with an inappropriate age distribution."

For example, they point out that in the UK, men in their 80s are twice as likely as men in their 50s to get a PSA test, even though men in the older age group are far less likely to have benefit and far more likely to experience harm from treatment. Similarly, in France, nearly one third of men over 40 get an annual PSA test, with the highest incidence of PSA testing in men over age 70. There are also high rates of PSA testing in men over 70 in Italy, Germany, and Ireland.

"A key problem is that, in current routine care — and despite guidelines to the contrary — most men with an abnormal PSA result have prostate biopsy, even though only a minority will have aggressive prostate cancer," Vickers and colleagues write. "Furthermore, most men with biopsy-detected cancers have either surgery or radiotherapy (with or without androgen deprivation therapy) even if they have low risk tumors that are unlikely to cause cancer related morbidity or mortality."

In addition, informed-choice PSA testing may lead to health inequities, the team comments, citing data from the US, Canada, and Switzerland showing an inverse association between income and education and the likelihood of PSA testing. Also, in the US and Canada, men from ethnic minority groups are less likely to have PSA testing.

Comprehensive Risk-Based Program

Vickers and colleagues propose that a "comprehensive, risk-based prostate cancer detection program based on best evidence on how to use PSA testing and manage subsequent diagnostic follow-up and treatment could reduce overdiagnosis and overtreatment."

"Such a program would restrict testing to men (and those not identifying as male but who have a prostate) aged 50-70, define testing intervals by PSA levels, stop testing early for those with lower PSA, offer biopsy only to those identified as at high risk of aggressive disease after a secondary test (such as magnetic resonance imaging [MRI] or blood markers), and limit treatment to those with high Gleason grade tumors," they write.

'Sound Analysis'

Two experts who were not involved with the BMJ paper applaud the suggestions made in comments posted on the UK Science Media Centre.

Benjamin W. Lamb, MBBS, MA, PhD, a consultant urologist and surgeon at Barts Health NHS Trust in London, said the analysis conducted by the panel "is sound as there are known benefits from risk-adapted comprehensive screening trials in men aged 50-70, but discordance with current practice, meaning benefits and harms are not those seen in trials."

However, he also said that the strategies proposed by the authors would be unlikely to prevent older, well-informed men from requesting and getting a PSA test.

"In my view, the emphasis should be on engaging younger and at-risk men rather than restricting access for older men," he said, noting that the alternative proposal of restricting PSA testing "in my view, is not feasible."

Nick James, MBBS, PhD, professor of prostate and bladder cancer research at the Institute of Cancer Research, London, and consultant oncologist at the Royal Marsden NHS Foundation Trust, said,

"I agree with the authors and strongly support the implementation of a risk-based approach to PSA testing at a national level."

"There is an urgent need for a more equitable and targeted screening strategy, which could help address existing health disparities," James said. "Currently, individuals from economically disadvantaged backgrounds are less likely to undergo PSA testing. Men in their 50s or younger, who may stand to benefit more from these tests, are also less likely to receive PSA tests compared to older men who benefit less. Linked to better diagnostic pathways with MRI, already standard in the UK, potential harms from overdiagnosis and overtreatment can be mitigated."

The analysis was supported in part by the US National Institutes of Health/National Cancer Institute with a Cancer Center Support Grant to MSKCC, and NIH grants to co-authors. Vickers is a co-inventor of the 4Kscore, a commercial test for predicting prostate biopsy outcome. He receives royalties from sales of the test and owns stock options in OPKO, which offers the test. Co-author James W.F. Catto has received reimbursement for consultancy from AstraZeneca, Ferring, Roche, and Janssen; speaker fees from BMS, MSD, Janssen, Astellas, Nucleix, and Roche; honoraria for membership of advisory boards for Ferring, Roche, Gilead, Photocure, BMS, QED therapeutics and Janssen; and research funding from Roche.

BMJ. Published online May 17, 2023. Excerpt

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.

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