Faculty Bibliography

OBJECTIVE: To present an effective approach to the early detection of lethal prostate cancer using longitudinal data on prostate-specific antigen (PSA) and its rate of change, i.e. PSA velocity (PSAV). This longitudinal approach might also be extendible to other biomarkers. SUBJECTS AND METHODS: PSAV was calculated using five techniques for 634 subjects with at least three PSA measurements in a longitudinal ageing study, censoring PSA levels of > 10 ng/mL. The efficacy for predicting death from prostate cancer was assessed with concordance indices and by using net reclassification improvement (NRI), which indicated the net increase in sensitivity and specificity when adding a biomarker to a base Cox proportional hazards model. The PSAV techniques were compared for the 5-10 years before the clinical diagnosis of prostate cancer. The most effective technique was then applied at the transition point when each man's PSA history curve transformed from linear to exponentially increasing, and its predictive value was compared to that of concurrent PSA level. RESULTS: A PSA transition point was found in 522 (82%) of the 634 men, including all 11 who died from prostate cancer. At the transition point, the mean PSA level was 1.4 ng/mL, and PSAV but not PSA level was significantly higher among men who died from prostate cancer than among men who did not (P = 0.021 vs P = 0.112; Wilcoxon two-sample test). At the transition point, adding PSAV to a base model consisting of age and date of diagnosis improved the concordance index by 0.05, and significantly improved the overall sensitivity and specificity (NRI, P = 0.028), while adding PSA level to the same base model resulted in little improvement (concordance index increase < 0.01 and NRI P = 0.275). CONCLUSION: When the shape of a man's PSA history curve changes from linear to exponential, PSAV might help in the early identification of life-threatening prostate cancer at a time when PSA values are still low in most men.