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Just How Effective Is PSA Screening?

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NEW ORLEANS — Prostate cancer screening with prostate-specific antigen (PSA) blood testing appears to have a more favorable benefit-to-harm trade-off than originally estimated, particularly among Black men, according to research presented here.

Using the most conservative assumptions about the benefits of screening, investigators found that among men of all races, one death was prevented for every 11 to 14 men diagnosed with prostate cancer and for every 7 to 11 men treated for the disease, reported Spyridon Basourakos, MD, of Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center in New York City, at the annual meeting of the American Urological Association.

According to the results, which were simultaneously published in NEJM Evidence, the benefit-to-harm ratio was even better for Black men, with PSA testing preventing one death for every 8 to 12 men diagnosed with prostate cancer and one death for every 5 to 9 men treated for it.

Basourakos said the data were much more favorable than estimates provided in earlier studies.

“The main take-home message is that PSA screening should be performed, particularly for men at high risk for prostate cancer, like Black men, men with a family history of prostate cancer, or men that have germline mutations,” Basourakos told MedPage Today. “These men should have discussions about the risk and benefits of screening, and engage in a shared decision-making process with urologists at the age of 40 or 45, depending on the guidelines.”

The rationale for the study, he and his colleagues noted, was that while randomized trial data support a significant mortality benefit with PSA testing, it’s uncertain how much of that benefit is due to PSA screening, and how that benefit measures up against potential harms such as overdiagnosis and overtreatment.

A 2009 analysis of prostate cancer diagnosis and treatment in the two decades (1986-2005) after the introduction of PSA screening, which used “the most optimistic assumption” that all reductions in cancer deaths after 1986 were attributable to screening, calculated that 23 men would be diagnosed and 18 would be treated for every prostate cancer death prevented.

However, said Basourakos, “we know prostate cancer has a very long natural history compared to other cancers, so the benefit of screening is going to be seen many years down the road.”

For the study, his team updated that 2009 calculation with another 11 years of data through 2016, and developed a microsimulation model to recreate the U.S. male population and come up with calculations based on two different scenarios — one in which all prostate cancer deaths were attributed to screening; and a second, more conservative, scenario that assumed half of prostate cancer deaths were prevented by screening.

Across races, the researchers estimated that 1.5-1.9 million prostate cancers were overdiagnosed by 2016, while 0.9-1.5 million were overtreated. The corresponding estimates for Black men were 320,000 overdiagnosed and 230,000 overtreated. Over this period, prostate cancer mortality initially rose, and then declined relative to 1986, with 270,000 fewer deaths among men of all races and 55,000 fewer deaths among Black men.

The more conservative estimate resulted in the lower numbers needed to diagnose and treat to avoid one cancer death described earlier. However, under a scenario in which screening prevented all deaths, the numbers needed to diagnose and treat to avoid one cancer death were reduced to 7 and 6, respectively, for all men, and 6 and 4 for Black men.

Basourakos noted that the argument against PSA screening has emphasized the resulting overdiagnosis and overtreatment. “This is true,” he said. “There is a fair amount of overdiagnosis and overtreatment, but we don’t think the solution is to attack PSA screening.”

“It’s better to try to reduce the amount of overdiagnosis and overtreatment,” he continued. “I think the solution is to continue PSA screening and to be more selective in how we manage patients after diagnosis. How do we do better active surveillance? How do we use biomarkers and MRI? PSA screening is not the enemy; we just need to use it better.”

In an editorial accompanying the paper in NEJM Evidence, one of the authors of the 2009 analysis, H. Gilbert Welch, MD, now of Brigham and Women’s Hospital in Boston, and Adewole Adamson, MD, MPP, of the University of Texas in Austin, noted that the study’s finding that the benefit-harm tradeoff will be more favorable for Black men “is certainly correct,” and addressed the pros and cons of whether recommendations for cancer screening should differentiate among individuals based on race.

However, the editorial continued, in the context of health disparities, cancer screening “is a weak intervention, at best, and comes with numerous side effects: anxiety, false alarms, overdiagnosis, overtreatment, and expense,” and also “distracts clinicians from the sick and siphons resources away from interventions that genuinely reduce health disparities.”

“If we were really serious about addressing life-expectancy disparities, we would focus less on disease among old persons (e.g., in Black men, the median age of prostate cancer death is 76 years, 4 years older than their average life expectancy) and more on supporting the young, particularly children and their parents,” Welch and Adamson wrote. “In addition, we would focus less on further expanding medical care, and more on addressing the social determinants of health.”

  • Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

Basourakos had no disclosures.

A co-author reported relationships with the American Cancer Society, the American Urological Association Foundation, Bristol Myers Squibb, and the Damon Runyon Cancer Research Foundation.

Welch reported receiving royalties from three books.

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