Low Rates of PSA Screening Linked to Increase in Metastatic Prostate Cancer

SAN ANTONIO — A study of men treated in Veterans Health Administration facilities suggested that lower prostate-specific antigen (PSA) screening rates were associated with subsequent increased rates of metastatic prostate cancer.

Across 128 facilities, PSA screening rates declined from 47% in 2005 to 37% in 2019, which was observed across all ages and races, reported Brent S. Rose, MD, of the University of California San Diego, during a press briefing at the American Society for Radiation Oncology (ASTRO) annual meeting. The study was also published in JAMA Oncology.

The long-term non-screening rate, representing patients not receiving a PSA test in the previous 3 years, increased from a low of 20.9% in 2009 to a high of 33.2% in 2019.

At the same time, age-adjusted metastatic prostate cancer incidence rates rose from 4.6 cases per 100,000 men in 2008 to a high of 8.2 cases per 100,000 in 2017, with that increase driven by men in the 55-69 and over-70 age groups.

“And when you look at facility-by-facility comparisons, the facilities that had maintained PSA screening rates at higher levels had lower rates of metastatic disease, and facilities that had lower rates of PSA screening had higher rates of metastatic disease,” Rose said.

Specifically, the researchers found that higher facility-level PSA screening rates were associated with lower subsequent metastatic prostate cancer rates 5 years later (incidence rate ratio [IRR] 0.91 per 10% increase in PSA screening rate, 95% CI 0.87-0.96, P<0.001). On the other hand, higher long-term non-screening rates were associated with higher metastatic prostate cancer incidence rates at 5 years (IRR 1.11 per 10% increase in long-term non-screening rate, 95% CI 1.03-1.19, P=0.01).

The rationale for the study, Rose explained, was simply that PSA screening “is controversial.”

Much of that, he said, can be traced back to two large randomized PSA screening trials — the European ERSPC trial, which demonstrated lower incidence of metastatic disease with PSA screening compared with usual care, and the U.S.-based PLCO study, which found no benefit of PSA screening in decreasing metastatic disease or mortality versus usual care.

Jeff M. Michalski, MD, of the Washington University School of Medicine in St. Louis and president-elect of ASTRO, said that in 2012 the U.S. Preventive Services Task force (USPSTF) “embraced” the PLCO trial and issued a statement recommending against PSA screening.

However, both Michalski and Rose noted that although the PLCO trial was supposed to compare PSA screening with a control arm of no screening, it was limited by high rates of PSA screening in the control arm.

“Clinical trials are really the gold standard,” Rose said. “Our data is much more consistent with the European trial, which showed the benefit of PSA screening. And it does support the hypothesis that the American study didn’t show such a big difference because there was a lot of PSA screening happening in both the control and intervention arms. Essentially both sides of the group were getting PSA screening.”

“Because of those two diverging studies, there have been guideline changes and a lot of differences in national variations in who gets PSA screening,” Rose said. “We wanted to look at real-world data — was PSA screening associated with metastasis for prostate cancer?”

The team analyzed data from 128 facilities in the VA health system on annual facility- and system-level PSA screening rates, system- and facility-level long-term non-screening rates, and age-adjusted incident rates of metastatic cancer from 2005 to 2019.

At the start of the study in 2005, there were 4.7 million men in the cohort, and by the end of the study in 2019, the cohort had grown to 5.4 million men. In 2012, the median proportion of Black patients was 9.2%, while 76.7% were white. The median proportion of patients ages 70 or older was 33.9%.

The USPSTF released an updated recommendation statement in 2018, advising that the decision to undergo PSA screening should be an individual one for men ages 55 to 69, and that physicians shouldn’t screen men who do not express that preference. It continues to recommend against PSA screening for men 70 and older.

“This study is very important in that it showed that in groups of patients where screening was not encouraged or not practiced, we saw an increase in patients presenting with late stages of prostate cancer — late stages of prostate cancer that are not curable and will likely lead to an increased rate of prostate cancer mortality in this population of patients who were not given the opportunity to be screened,” Michalski noted.

“I hope this data will give an opportunity for the USPSTF to re-examine their recommendations,” he added. “While there is the risk of overdiagnosis and overtreatment, there’s also a risk of underdiagnosis and undertreatment by completely abandoning the idea of PSA screening altogether.”