COST-BENEFIT ANALYSIS OF TOTAL, FREE/TOTAL, AND COMPLEXED PROSTATE-SPECIFIC ANTIGEN FOR PROSTATE CANCER SCREENING LARS ELLISON, CAROL D. CHELI, STEVEN BRIGHT, ROBERT W. VELTRI, AND ALAN W. PARTIN ABSTRACT Refinements in prostate-specific antigen (PSA) through the use of its derivatives have augmented early detection rates of prostate cancer. However, these improvements are coupled with relatively large increases in unit cost per detected cancer. We used decision-analytic modeling to determine the most appropriate PSA derivative for population-based screening. We constructed a decision-analytic model to determine the PSA derivative with the highest cost-benefit ratio for prostate cancer screening. We defined 5 screening strate- gies: total PSA (tPSA) 4.0 ng/mL; free PSA/tPSA (f/tPSA) in conjunction with tPSA; and complexed PSA (cPSA) 3.8, 3.4, and 3.0 ng/mL. Prostate cancer prevalence, false-positive rates, and false-negative rates for each test strategy were calculated from a database of 2138 men. The direct costs were obtained from literature review and our department of clinical chemistry. The derivative cPSA with a positive threshold of 3.8 ng/mL was the dominant strategy. The average cost of screening was $138.93. The strategy of tPSA became dominant when the cost of cPSA was $35.00 or the cost of a prostate biopsy was $67.30. To match the false-negative rate of tPSA 4.0 ng/mL, a cPSA threshold of 3.0 ng/mL is necessary (sensitivity 92.5%). At this level, the marginal cost increase over tPSA is $9.40. The dominant strategy for population- based prostate cancer screening is use of cPSA with a positive threshold of 3.8 ng/mL. The use of cPSA with a threshold of 3.0 ng/mL identifies a similar number of cancers with fewer biopsies than tPSA at 4.0 ng/mL. UROLOGY 60 (Suppl 4A): 42–46, 2002. © 2002, Elsevier Science Inc. P rostate-specific antigen (PSA) has changed our definitions and management of prostate can- cer. However, as a screening biomarker, total se- rum PSA (tPSA) has a poor positive predictive value because of a high false-positive rate. 1 Recog- nition of different molecular forms of PSA (free PSA [fPSA] and complexed PSA [cPSA]) has led to incremental improvements in these test character- istics. 2 Identification of appropriate positive thresholds for these PSA isoforms may allow clini- cians to more accurately identify patients for bi- opsy and greatly diminish the numbers of unnec- essary biopsies. The unmeasured corollary of the introduction of improved and advanced biomarkers is increased cost of screening. The cost relation is complicated by the relative contribution of downstream diag- nostic tests (specifically the transrectal ultrasound [TRUS]-guided biopsy). In addition, this cost rela- tion is amplified by the necessary broad definition of the population at risk (men 50 years old). We used (1) a large multi-institutional patient sample of men, aged 40 to 75 years, who under- went standard screening and prostate biopsy; (2) cost and utility data from the literature; and (3) decision-analytic modeling. This information was used to determine, from a societal perspective, which PSA isoform and serum threshold of positiv- ity is most cost-beneficial for prostate cancer screening. METHODS PATIENT SAMPLE We merged 2 contemporary datasets, the first from UroCor Labs (Oklahoma City, OK) and the second from Bayer Diag- nostics (Tarrytown, NY). The UroCor data have been previ- ously described. 3 For the Bayer dataset, the study sites were: From the Brady Urological Institute, the Johns Hopkins Medical Institution, Baltimore Maryland, USA (LE, RWV, AWP); Robert Wood Johnson Clinical Scholars Program, the Johns Hopkins Medical Institution, Baltimore Maryland, USA (LE); Bayer Cor- poration, Tarrytown, New York, USA (CDC); and UroCor, Inc., Oklahoma City, Oklahoma, USA (SB) Reprint requests: Lars Ellison, MD, Brady Urological Institute, Johns Hopkins-RWJ Program, 600 North Wolfe Street, Carnegie 291, Baltimore, MD 21287. E-mail: lelliso2@jhmi.edu © 2002, ELSEVIER SCIENCE INC. 0090-4295/02/$22.00 42 ALL RIGHTS RESERVED PII S0090-4295(02)01694-1