External validation of the Prostate Cancer Prevention Trial and the European Randomized Study of Screening for Prostate Cancer risk calculators in a Chinese cohort

Abstract

Several prediction models have been developed to estimate the outcomes of prostate biopsies. Most of these tools were designed for use with Western populations and have not been validated across different ethnic groups. Therefore, we evaluated the predictive value of the Prostate Cancer Prevention Trial (PCPT) and the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators in a Chinese cohort. Clinicopathological information was obtained from 495 Chinese men who had undergone extended prostate biopsies between January 2009 and March 2011. The estimated probabilities of prostate cancer and high-grade disease (Gleason >6) were calculated using the PCPT and ERSPC risk calculators. Overall measures, discrimination, calibration and clinical usefulness were assessed for the model evaluation. Of these patients, 28.7% were diagnosed with prostate cancer and 19.4% had high-grade disease. Compared to the PCPT model and the prostate-specific antigen (PSA) threshold of 4 ng ml(-1), the ERSPC risk calculator exhibited better discriminative ability for predicting positive biopsies and high-grade disease (the area under the curve was 0.831 and 0.852, respectively, P<0.01 for both). Decision curve analysis also suggested the favourable clinical utility of the ERSPC calculator in the validation dataset. Both prediction models demonstrated miscalibration: the risk of prostate cancer and high-grade disease was overestimated by approximately 20% for a wide range of predicted probabilities. In conclusion, the ERSPC risk calculator outperformed both the PCPT model and the PSA threshold of 4 ng ml(-1) in predicting prostate cancer and high-grade disease in Chinese patients. However, the prediction tools derived from Western men significantly overestimated the probability of prostate cancer and high-grade disease compared to the outcomes of biopsies in a Chinese cohort.

Figure 1

ROC curves of the risk calculators and the PSA threshold of 4 ng ml⁻¹ for prostate cancer (a) and high-grade disease (b) in the validation cohort (n=495). Pairwise comparisons of ROC curves are shown in the bottom-right corner of the figure. The table displays the sensitivity and specificity of each risk calculators at different cut-offs. For example, using the ERSPC risk calculator in this cohort, a cut-off of 30% corresponds to a sensitivity of 89.4% and a specificity of 49.0% in detecting prostate cancer. ERSPC, European Randomized Study of Screening for Prostate Cancer; PSA, prostate-specific antigen; ROC, receiver operating characteristic.

Figure 2

Calibration plots of the risk calculators in the validation cohort (n=495): ERSPC (a) and PCPT (b) risk calculators for prostate cancer; ERSPC (c) and PCPT (d) risk calculator for high-grade disease. The 45° dashed line represents an ideal prediction, in which the predicted and actual probabilities are identical. The actual performance of each risk calculator is represented by the blue dotted line. The red solid line indicates that the predicted risk was 20% higher than the observed probability. The spike histogram at the bottom of the figure shows the distribution of the individual predicted probabilities. ERSPC, European Randomized Study of Screening for Prostate Cancer; PCPT, Prostate Cancer Prevention Trial; ROC, receiver operating characteristic.

Figure 3

Decision curve analyses of the risk calculators and the PSA threshold of 4 ng ml⁻¹ in the validation cohort (n=495): net benefit (a) and reduction (b) curves for prostate cancer; net benefit (c) and reduction (d) curves for high-grade disease. The table displays the net benefit and reduction statistics at different threshold probabilities. For example, using the ERSPC risk calculator in this cohort, a threshold probability of 30% corresponds to a net benefit of 10.1% and a net reduction of 23.5% over the PSA cut-off of 4 ng ml⁻¹ in detecting prostate cancer. ERSPC, European Randomized Study of Screening for Prostate Cancer; PCPT, Prostate Cancer Prevention Trial; PSA, prostate-specific antigen.