Prostate cancer deaths can be prevented by targeted screening

United Kingdom: Screening men at higher genetic risk of prostate cancer could prevent nearly one in six deaths while minimizing unnecessary treatments for harmless tumors, according to a recent study in the journal PLoS Medicine. This would potentially reduce overdiagnosis, improve the benefit–harm tradeoff and the cost-effectiveness of a prostate cancer screening program.

Prostate cancer is the second most commonly occurring cancer in men and the fourth most commonly occurring cancer overall. There were 1.3 million new cases in 2018. A blood test that detects prostate-specific antigen (PSA) levels can be used for screening of prostate cancer. However, the test is not able to accurately distinguish between dangerous cancer from harmless ones leading to unnecessary operations and missed cancer that is harmful.

The United States Preventive Services Task Force supports individualized decision-making for prostate-specific antigen (PSA)-based screening in men aged 55–69. Knowing how the potential benefits and harms of screening vary by an individual's risk of developing prostate cancer could inform decision-making about screening at both an individual and population level.

This modeling study by Tom Callender, University College London, London, United Kingdom, and colleagues examined the benefit–harm tradeoffs and the cost-effectiveness of a risk-tailored screening program compared to age-based and no screening.

For the study, the researchers created a hypothetical cohort of 4.5 million men, representing the number of men aged 55 to 69 in England, and simulated the outcomes of introducing screening into this population. Outcomes included prostate cancer deaths averted, unnecessary diagnoses and screening costs were compared for no screening, universal age-based screening and more targeted screening using a range of thresholds of genetic risk.

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Key findings of the study include:

• Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272) at the expense of 94,831 overdiagnosed cancers.


• Age-based screening was the least cost-effective strategy studied.


• The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%.


• At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384) but averted 6.3% fewer (9,695) deaths from prostate cancer by comparison with age-based screening.


• Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively.


• The cost-effectiveness of risk-tailored screening improved as the threshold rose.

"The optimal scenario would be to screen men with a 4-7% risk of getting prostate cancer over the next 10 years—that is, between roughly half and a quarter of all men aged 55 to 69," concluded the researchers. Screening all men in that age group would result in the most deaths averted (20%) but, along with the extra cost, would also lead to a large number of unnecessary diagnoses, with nearly one in three cancers detected by screening being harmless.

Researchers said targeted screening based on genetic risk would require an evolution of screening services. They noted that inviting people for screening at different ages may affect screening delivery and that the broader impact of screening using genetic risk required further research.

"The ideal threshold for risk-tailored screening will depend on the societal judgment of the tradeoff between the benefits and harms of screening," wrote the researchers.

The study, "Polygenic risk-tailored screening for prostate cancer: A benefit–harm and cost-effectiveness modelling study," is published in the journal PLoS Medicine.

DOI: https://doi.org/10.1371/journal.pmed.1002998