{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:47:38Z","timestamp":1777916858253,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2018,3,31]],"date-time":"2018-03-31T00:00:00Z","timestamp":1522454400000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.sagepub.com\/licence-information-for-chorus"}],"funder":[{"name":"Early Detection Research Network","award":["7-U01-CA-113913-09"],"award-info":[{"award-number":["7-U01-CA-113913-09"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CMMI0844511"],"award-info":[{"award-number":["CMMI0844511"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE 1256260"],"award-info":[{"award-number":["DGE 1256260"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Michigan MCubed program"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Med Decis Making"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>Background. New cancer biomarkers are being discovered at a rapid pace; however, these tests vary in their predictive performance characteristics, and it is unclear how best to use them. Methods. We investigated 2-stage biomarker-based screening strategies in the context of prostate cancer using a partially observable Markov model to simulate patients\u2019 progression through prostate cancer states to mortality from prostate cancer or other causes. Patients were screened every 2 years from ages 55 to 69. If the patient\u2019s serum prostate-specific antigen (PSA) was over a specified threshold in the first stage, a second stage biomarker test was administered. We evaluated design characteristics for these 2-stage strategies using 7 newly discovered biomarkers as examples. Monte Carlo simulation was used to estimate the number of screening biopsies, prostate cancer deaths, and quality-adjusted life-years (QALYs) per 1000 men. Results. The all-cancer biomarkers significantly underperformed the high-grade cancer biomarkers in terms of QALYs. The screening strategy that used a PSA threshold of 2 ng\/mL and a second biomarker test with high-grade sensitivity and specificity of 0.86 and 0.62, respectively, maximized QALYs. This strategy resulted in a prostate cancer death rate within 1% of using PSA alone with a threshold of 2 ng\/mL, while reducing the number of biopsies by 20%. Sensitivity analysis suggests that the results are robust with respect to variation in model parameters. Conclusions. Two-stage biomarker screening strategies using new biomarkers with risk thresholds optimized for high-grade cancer detection may increase quality-adjusted survival and reduce unnecessary biopsies.<\/jats:p>","DOI":"10.1177\/0272989x17696996","type":"journal-article","created":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T20:39:27Z","timestamp":1490992767000},"page":"815-826","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Two-Stage Biomarker Protocols for Improving the Precision of Early Detection of Prostate Cancer"],"prefix":"10.1177","volume":"37","author":[{"given":"Christine L.","family":"Barnett","sequence":"first","affiliation":[{"name":"Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI (CLB, BTD)"},{"name":"Department of Urology, University of Michigan, Ann Arbor, MI (SAT, JTW, TMM, JEM, BTD)"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI (SAT)"},{"name":"Department of Industrial & Systems Engineering, North Carolina State University, Raleigh, NC (DJU)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott A.","family":"Tomlins","sequence":"additional","affiliation":[{"name":"Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI (CLB, BTD)"},{"name":"Department of Urology, University of Michigan, Ann Arbor, MI (SAT, JTW, TMM, JEM, BTD)"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI (SAT)"},{"name":"Department of Industrial & Systems Engineering, North Carolina State University, Raleigh, NC (DJU)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Underwood","sequence":"additional","affiliation":[{"name":"Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI (CLB, BTD)"},{"name":"Department of Urology, University of Michigan, Ann Arbor, MI (SAT, JTW, TMM, JEM, BTD)"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI (SAT)"},{"name":"Department of Industrial & Systems Engineering, North Carolina State University, Raleigh, NC (DJU)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI (CLB, BTD)"},{"name":"Department of Urology, University of Michigan, Ann Arbor, MI (SAT, JTW, TMM, JEM, BTD)"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI (SAT)"},{"name":"Department of Industrial & Systems Engineering, North Carolina State University, Raleigh, NC (DJU)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd M.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI (CLB, BTD)"},{"name":"Department of Urology, University of Michigan, Ann Arbor, MI (SAT, JTW, TMM, JEM, BTD)"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI (SAT)"},{"name":"Department of Industrial & Systems Engineering, North Carolina State University, Raleigh, NC (DJU)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Montie","sequence":"additional","affiliation":[{"name":"Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI (CLB, BTD)"},{"name":"Department of Urology, University of Michigan, Ann Arbor, MI (SAT, JTW, TMM, JEM, BTD)"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI (SAT)"},{"name":"Department of Industrial & Systems Engineering, North Carolina State University, Raleigh, NC (DJU)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian T.","family":"Denton","sequence":"additional","affiliation":[{"name":"Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI (CLB, BTD)"},{"name":"Department of Urology, University of Michigan, Ann Arbor, MI (SAT, JTW, TMM, JEM, BTD)"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI (SAT)"},{"name":"Department of Industrial & Systems Engineering, North Carolina State University, Raleigh, NC 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