Thomas Callender1, Mark Emberton2, Stephen Morris3, Paul D P Pharoah3,4, Nora Pashayan1. 1. Department of Applied Health Research, University College London, London, United Kingdom. 2. Division of Surgery and Interventional Science, University College London, London, United Kingdom. 3. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 4. Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
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% (12 370; 95% UI, 11 100-13 670) fewer overdiagnoses, and 33.8% (650 500; 95% UI, 463 200-907 000) 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% (51 250; 95% UI, 46 070-56 890) fewer overdiagnosed cancers, respectively, and between 21.7% fewer MRIs (412 100; 95% UI, 411 400-412 900) and 53.5% fewer biopsies (1 016 000; 95% UI, 1 010 000-1 022 000), respectively, compared with MRI-first age-based screening. The most cost-effective strategies at willingness-to-pay thresholds of £20 000 (US $26 000) and £30 000 (US $39 000) 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.
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% (12 370; 95% UI, 11 100-13 670) fewer overdiagnoses, and 33.8% (650 500; 95% UI, 463 200-907 000) 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% (51 250; 95% UI, 46 070-56 890) fewer overdiagnosed cancers, respectively, and between 21.7% fewer MRIs (412 100; 95% UI, 411 400-412 900) and 53.5% fewer biopsies (1 016 000; 95% UI, 1 010 000-1 022 000), respectively, compared with MRI-first age-based screening. The most cost-effective strategies at willingness-to-pay thresholds of £20 000 (US $26 000) and £30 000 (US $39 000) 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.
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