Abstract

Abstract Background In men with suspected prostate cancer, an MRI-first diagnostic pathway has been shown to reduce the clinically insignificant cancers and increase the clinically significant cancers detected, whilst obviating the need for approximately one-third of biopsies. We estimate the impact that an MRI-first diagnostic pathway would have on both age-based and precision screening. Methods Adapting a life-table model, we simulated hypothetical cohorts of 4.48 million men in England receiving no screening, age-based screening, or precision screening based on age and polygenic risk profile strategies. We analysed both age-based and precision screening strategies using MRI- and biopsy-first diagnostic pathways. If screened, men had a PSA test every four years, either from age 55 (age-based screening) or from the age that a man reached the risk threshold (precision screening) to age 70. Precision screening risk thresholds were varied between a 2% and 10% 10-year absolute risk of developing prostate cancer. We compared the benefit (prostate cancer deaths prevented) harm (overdiagnosis) trade-offs of different screening strategies. We assessed cost-effectiveness using net monetary benefit and incremental cost-effectiveness ratios (ICER). All analyses were probabilistic, from a health service perspective, and with both costs and benefits discounted at 3.5% per annum. Results An MRI-first diagnostic pathway reduced overdiagnosis in age-based screening by 13.8% and avoided 26.0% of biopsies, whilst preventing 1.8% more deaths from prostate cancer, generating more QALYs and lowering the costs of screening by 8.4%. These gains required a 3.7-fold increase in the number of MRI scans performed in an age-based screening programme. When comparing age-based and precision screening both using an MRI-first diagnostic pathway, precision screening reduced overdiagnosis by a further 10.5% to 71.3% and the number of MRI scans and biopsies by between 22.9% and 57.3%, at 10-year absolute risk thresholds of 2% and 10%, respectively, whilst generating more QALYs at all risk thresholds below 5%. MRI-first precision screening prevented more deaths than biopsy-first age-based screening at a risk threshold of 2%, but prevented between 1.7% and 15.3% fewer deaths from prostate cancer at risk thresholds of 2% and 10%, respectively, when compared with MRI-first age-based screening. All MRI-first precision screening strategies had a higher net monetary benefit than MRI-first age-based screening, whilst all MRI-first precision screening strategies using a risk threshold of 2.5% or greater had ICERs of <£20,000 ($26,000) per QALY gained, by comparison with no screening. Conclusion An MRI-first diagnostic pathway could improve the benefit-to-harm profile of screening for prostate cancer and these benefits were compounded by precision screening. Prospective evaluation is necessary to verify these findings. Citation Format: Thomas Callender, Mark Emberton, Steve Morris, Paul Pharoah, Nora Pashayan. MRI-first screening for prostate cancer: A benefit-harm and cost-effectiveness analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3523.

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