New ACS Guidelines Take Firmer Stance on PSA Screening

In new prostate cancer screening guidelines , the American Cancer Society (ACS) has called for routine prostate-specific antigen (PSA) testing of average-risk men every 2 years from ages 50 through 69 years. Among the 10 main recommendations, the group also advises repeat testing 2 weeks to 3 months later for men with PSA levels of 3 ng/mL or higher to confirm persistent elevations before further evaluation.

The recommendations are a major departure from the group’s last guidelines in 2010 , which were far less prescriptive and recommended that men be told about the uncertainties, risks, and potential benefits of screening, and then make a decision with their healthcare provider about going forward.

ACS’s new advice also goes further than the US Preventive Services Task Force’s (USPSTF's) most recent guidelines from 2018 , which said the decision to screen should be an individual one, given the small potential benefit of reducing the chance of death from prostate cancer, balanced against the risk of overtreating clinically insignificant disease.

USPSTF made no suggestions for screening intervals in 2018 and gave routine screening a grade of C, given the uncertainties. What has changed over the years, leading to ACS’s more certain and detailed advice, is that “we have more confidence now about when screening should start, what the interval should be, and that if it's done properly, the benefits outweigh the risks,” said ACS cancer epidemiologist Robert Smith, PhD , senior author of both the new and the 2010 guidelines.

“We've got quite convincing data that screening is associated with reduction in the incidence rate of advanced disease and deaths, and, over time, there's been real progress in the steps that you can take to avoid detecting and overtreating low-risk disease,” Smith told Medscape Medical News .

Such steps include repeat testing of elevated PSA levels, MRI and biomarker evaluation of persistently elevated values, and active surveillance for low-risk disease, all measures included in ACS’s new guidelines. The 2025 update of the European ERSPC trial was particularly influential to the ACS, after it showed the endurance of the mortality reduction with routine screening over nearly a quarter century of follow-up.

“Once the ERSPC data were out, we said it’s time for an update,” Smith said. At the same time, it has become clear that the failure of the US PLCO trial to show a benefit of screening was because the trial was flawed: PSA testing in the control group was nearly as high as in the screening arm, and quite a few men in the screening arm with positive findings had no additional workup, among other issues.

“So, we don't have this distraction” anymore that one major trial was positive and the other major trial was negative, which led to uncertainty, Smith said. ACS’s new guidelines are largely in line with 2026 prostate cancer screening updates from two other influential groups, the American Urological Association and the National Comprehensive Cancer Network (NCCN).

There are some differences in the details. NCCN, for instance, recommends routine screening for average-risk men from age 45 to 75 years. “We certainly favor our recommendations compared with those of other organizations,” but overall “they share more in common than they do in differences, and an effort to achieve high adherence to any one of these [guidelines] would be better for men than the situation we are in right now,” where self-reported screening rates in the general public are only about 35%-40%, Smith said.

Ultimately, he added, “we hope that [our] new recommendations result in an increase in the uptake of prostate cancer screening. It saves lives, it reduces the risk of advanced disease, and we have ways to avoid the risks.” Additional recommendations from ACS include, among others: PSA-based screening every year from age 45 through 69 years for Black men and for non-Black men with a strong family history of prostate cancer; Individualized decision-making for men age 70 through 74 years that considers the uncertain balance of benefits and harms, overall health status, values, and preferences; and No prostate cancer screening in men age 75 years or older or in men at any age with less than a 10-year life expectancy.

USPSTF, meanwhile, is updating its 2018 guidelines. Smith had no relevant disclosures. M.

Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net