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Prostate Cancer Modeling Study Supports Precision Screening Approach

NEW YORK – A new mathematical analysis suggests prostate cancer screening programs tailored to an individual's polygenic risk of the disease may catch disease and prevent deaths, while decreasing the overdiagnosis compared to age-based screening.

"Our study shows that targeted screening can reduce unnecessary diagnoses while helping to prevent people dying from the disease by enabling earlier detection," senior author Nora Pashayan, an applied health researcher at University College London, said in a statement.

To explore the potential benefit-harm and cost-effectiveness of various prostate cancer screening strategies, Pashayan and colleagues in the UK modeled the potential deaths prevented, overdiagnoses, direct health care costs, and more in a simulated cohort of nearly 4.5 million 55- to 69-year-old men in England, followed until the age of 90.

The team found that age-based screening — including regularly-scheduled prostate specific antigen (PSA) tests — would be expected to prevent the most prostate cancer deaths, but that strategy was less cost-effective than both the genetics-guided approach and the no-screening strategy.

The group's modeling pointed to a rise in quality-adjusted life years, along with a dip in overdiagnoses, in the genetic risk-informed screening simulation that relied on a polygenic risk score that spanned more than 160 SNPs, particularly when focusing on individuals with more than 4 percent risk of developing the disease over the coming decade.

The anticipated decline in unnecessary diagnoses, reduced cost, and enhanced quality of life in the polygenic risk-informed scenario came at the expense of 6.3 percent fewer prostate cancer deaths being prevented compared to age-based screening, the researchers noted in their study, published online today in PLOS Medicine.

Still, polygenic risk-based prostate cancer screening would be expected to significantly curb deaths compared with a screening-free strategy, the team reported, since it is estimated that some 49 percent of prostate cancers occur in those with polygenic risk scores placing them in the top 20 percent of prostate cancer risk.

"This modeling analysis has shown that precision screening based on age and polygenic risk could reduce overdiagnosis whilst preserving most of the mortality benefits of age-based screening for prostate cancer," the authors wrote.

Recent guidelines from the US Preventive Services Task Force suggest PSA testing be considered for men between 55 and 69, while the UK does not currently have a national prostate cancer screening program in place.

"Prostate cancer is a leading cause of death from cancer in men in the UK, but screening is not performed because the harm of overdiagnosis is thought to outweigh the benefits," Pashayan said.

Authors of the new analysis cautioned that additional, prospective studies are needed to confirm the current modeling results, and noted that the "optimal threshold will depend on societal judgements of the appropriate balance of benefits-harms, and cost-effectiveness."

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