Change in PSA velocity is a predictor of overall survival in men with biochemically-recurrent prostate cancer treated with non-hormonal agents: Combined analysis of four phase-2 trials

BACKGROUND: Multiple phase-2 trials in men with biochemically-recurrent prostate cancer (BRPC) have assessed the impact of non-hormonal agents on PSA kinetics. We have previously demonstrated that changes in PSA kinetics correlate with metastasis-free survival; however, it is unknown whether these changes also correlate with overall survival (OS). METHODS: We performed a combined retrospective analysis of 146 men with BRPC treated on phase-2 trials using one of four investigational drugs: lenalidomide (n=60), marimastat (n=39), ATN-224 (n=22), and imatinib (n=25). We examined factors influencing OS, including within-subject changes in PSA kinetics (PSA slope, PSA doubling time, and PSA velocity) before and 6 months after treatment initiation. RESULTS: After a median follow up of 83.1 months, 49 of 146 men had died. In univariate Cox regression analysis, two factors were associated with OS: baseline PSA velocity and change in PSA velocity on therapy. In a landmark multivariable model, stratified by study (which controlled for age, Gleason score, type of local therapy, and use of ADT prior to metastases), baseline PSA velocity and increase in PSA velocity on therapy remained independent predictors of OS. Median OS for men with an increase in PSA velocity on treatment was 115.4 months and was not reached for men with a decrease in PSA velocity (HR=0.47, 95% CI 0.25 to 0.88; P=0.02). CONCLUSIONS: This hypothesis-generating study suggests that within-subject changes in PSA velocity after initiation of non-hormonal therapy may correlate with OS in men with BRPC. If validated in prospective trials, change in PSA velocity may represent a reasonable intermediate endpoint for screening new agents in these patients.