The benefits, harms, and cost-effectiveness of age-based and risk-stratified screening for prostate cancer with MRI

Background Prostate cancer screening remains contested. MRI-first screening may reduce overdiagnosis by detecting fewer insignificant cancers than PSA-based strategies. However, the benefits, harms, and cost-effectiveness of MRI-first prostate cancer screening remain uncertain. Methods We simulated age-based and risk-stratified MRI-first screening strategies. Risk-stratification involved either a polygenic risk score or a PSA test, with a PSA threshold of 1ng/ml or 3ng/ml considered positive. We conducted extensive scenario and sensitivity analyses to determine the robustness of conclusions to input parameters. Primary outcomes were prostate cancer deaths, overdiagnosed cancers, resource use, and cost-effectiveness (net health benefit from a healthcare perspective). Results Age-based MRI-first screening every 4 years from 55-69 years old could reduce prostate cancer deaths by 6 per 1,000 men, with 13% of screen-detected cancers overdiagnosed. However, this strategy required a 15-fold increase in MRI scans relative to no screening and was not cost-effective within a UK context. Risk-stratified screening using polygenic risk was more likely to be cost-effective, generate more QALYs, and lead to fewer overdiagnosed cancers than screening all men with MRI. At a willingness-to-pay (WTP) of {pound}25,000 per QALY gained, screening men aged 55 with a 10-year absolute risk of prostate cancer of [≥]5.6% had a greater NHB than no screening. Stratifying screening with PSA before MRI led to 6%-17% more overdiagnosed cancers than MRI-first screening, depending on the threshold for a positive PSA test (3ng/ml or 1ng/ml, respectively). But PSA stratification was not cost-effective at either a 1ng/ml or 3ng/ml threshold in a UK context. Conclusions MRI-first screening could reduce overdiagnosis and generate more QALYs than stratifying screening with PSA prior to MRI. But the additional resource requirements meant that risk-stratification is likely to be necessary for prostate cancer screening to be considered cost-effective in the UK.