Benefit, Harm, and Cost-effectiveness Associated with Magnetic Resonance Imaging before Biopsy in Age-based and Risk-stratified Screening for Prostate Cancer

Abstract

Importance: If magnetic resonance imaging (MRI) mitigates overdiagnosis of prostate cancer while improving the detection of clinically significant cases, including MRI in a screening program for prostate cancer could be considered. Objective: To evaluate the benefit-harm profiles and cost-effectiveness associated with MRI before biopsy compared with biopsy-first screening for prostate cancer using age-based and risk-stratified screening strategies. Design, Setting, and Participants: This decision analytical model used a life-table approach and was conducted between December 2019 and July 2020. A hypothetical cohort of 4.48 million men in England aged 55 to 69 years were analyzed and followed-up to 90 years of age. Exposures: No screening, age-based screening, and risk-stratified screening in the hypothetical cohort. Age-based screening consisted of screening every 4 years with prostate-specific antigen between the ages of 55 and 69 years. Risk-stratified screening used age and polygenic risk profiles. Main Outcomes and Measures: The benefit-harm profile (deaths from prostate cancer, quality-adjusted life-years, overdiagnosis, and biopsies) and cost-effectiveness (net monetary benefit, from a health care system perspective) were analyzed. Both age-based and risk-stratified screening were evaluated using a biopsy-first and an MRI-first diagnostic pathway. Results were derived from probabilistic analyses and were discounted at 3.5% per annum. Results: The hypothetical cohort included 4.48 million men in England, ranging in age from 55 to 69 years (median, 62 years). Compared with biopsy-first age-based screening, MRI-first age-based screening was associated with 0.9% (1368; 95% uncertainty interval [UI], 1370-1409) fewer deaths from prostate cancer, 14.9% (12370; 95% UI, 11100-13670) fewer overdiagnoses, and 33.8% (650500; 95% UI, 463200-907000) fewer biopsies. At 10-year absolute risk thresholds of 2% and 10%, MRI-first risk-stratified screening was associated with between 10.4% (7335; 95% UI, 6630-8098) and 72.6% (51250; 95% UI, 46070-56890) fewer overdiagnosed cancers, respectively, and between 21.7% fewer MRIs (412100; 95% UI, 411400-412900) and 53.5% fewer biopsies (1016000; 95% UI, 1010000-1022000), respectively, compared with MRI-first age-based screening. The most cost-effective strategies at willingness-to-pay thresholds of £20000 (US $26000) and £30000 (US $39000) per quality-adjusted life-year gained were MRI-first risk-stratified screening at 10-year absolute risk thresholds of 8.5% and 7.5%, respectively. Conclusions and Relevance: In this decision analytical model of a hypothetical cohort, an MRI-first diagnostic pathway was associated with an improvement in the benefit-harm profile and cost-effectiveness of screening for prostate cancer compared with biopsy-first screening. These improvements were greater when using risk-stratified screening based on age and polygenic risk profile and may warrant prospective evaluation..