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.
We investigated 2-stage biomarker-based screening strategies in the context of prostate cancer using a partially observable Markov model to simulate patients' 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's 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.
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.
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.
Medical decision making : an international journal of the Society for Medical Decision Making. 2017 Mar 31 [Epub]
Christine L Barnett, Scott A Tomlins, Daniel J Underwood, John T Wei, Todd M Morgan, James E Montie, Brian T Denton
Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI (CLB, BTD)., Department of Pathology, University of Michigan, Ann Arbor, MI (SAT)., Department of Industrial & Systems Engineering, North Carolina State University, Raleigh, NC (DJU)., Department of Urology, University of Michigan, Ann Arbor, MI (SAT, JTW, TMM, JEM, BTD).