Evaluating the PCPT risk calculator in ten international biopsy cohorts: results from the Prostate Biopsy Collaborative Group
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To evaluate the discrimination, calibration, and net benefit performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) across five European randomized study of screening for prostate cancer (ERSPC), 1 United Kingdom, 1 Austrian, and 3 US biopsy cohorts.
PCPTRC risks were calculated for 25,733 biopsies using prostate-specific antigen (PSA), digital rectal examination, family history, history of prior biopsy, and imputation for missing covariates. Predictions were evaluated using the areas underneath the receiver operating characteristic curves (AUC), discrimination slopes, chi-square tests of goodness of fit, and net benefit decision curves.
AUCs of the PCPTRC ranged from a low of 56% in the ERSPC Goeteborg Rounds 2–6 cohort to a high of 72% in the ERSPC Goeteborg Round 1 cohort and were statistically significantly higher than that of PSA in 6 out of the 10 cohorts. The PCPTRC was well calibrated in the SABOR, Tyrol, and Durham cohorts. There was limited to no net benefit to using the PCPTRC for biopsy referral compared to biopsying all or no men in all five ERSPC cohorts and benefit within a limited range of risk thresholds in all other cohorts.
External validation of the PCPTRC across ten cohorts revealed varying degree of success highly dependent on the cohort, most likely due to different criteria for and work-up before biopsy. Future validation studies of new calculators for prostate cancer should acknowledge the potential impact of the specific cohort studied when reporting successful versus failed validation.
KeywordsReceiver operating characteristic curve Risk, prostate cancer Calibration Net benefit
Statistics supported in part by funds from David H. Koch provided through the Prostate Cancer Foundation, the Sidney Kimmel Center for Prostate and Urologic Cancers SPORE grant from the U.S. National Cancer Institute [P50-CA92629], and a Cancer Center Support Grant for the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio [P30-CA054174]. Grants to support the work of the ERSPC include: European Union Grants SOC 95 35109, SOC 96 201869 05F022, SOC 97 201329, SOC 98 32241, the 6th Framework Program of the EU: PMark:LSHC-CT-2004-503011; and The Dutch Cancer Society (KWF 94-869, 98-1657, 2002-277, 2006-3518); The Netherlands Organisation for Health Research and Development (ZonMW-002822820, 22000106, 50-50110-98-311); The Prostate Cancer Research Foundation of Rotterdam (SWOP); Beckman-Coulter-Hybritech Inc; Abbott Pharmaceuticals, Sweden; Af Jochnick’s foundation; Catarina and Sven Hagstroms family foundation; Gunvor and Ivan Svensson’s foundation; Johanniterorden, King Gustav V Jubilée Clinic Cancer Research Foundation; Sahlgrenska University Hospital; Schering Plough, Sweden, Swedish Cancer Society (Contract numbers 09 0107, 080315 and 083455); and Wallac Oy, Turkku, Finland. The Tyrol study is supported by the International Agency for Research on Cancer, Lyon and the Tyrolean Prostate Cancer Early Detection Group. The SABOR project is supported by the San Antonio Center of Biomarkers of Risk for Prostate Cancer CA086402. The ProtecT study is funded by the UK NIHR Health Technology Assessment Programme (projects 96/20/06, 96/20/99).
Conflict of interest
The authors declare that they have no conflict of interest.
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