Time to biochemical progression predicts second events in high-risk prostate cancer

This study is a secondary analysis of a phase 3 randomized controlled trial involving 413 men with high-risk localized prostate cancer. Patients were randomized to receive androgen deprivation therapy (ADT) alone or ADT plus docetaxel and estramustine (DE). The primary outcome was relapse-free survival (RFS), but the main findings reported here are from parametric survival models and competing-risk analyses examining the prognostic value of time from randomization to biochemical progression (BP).

In the analysis of RFS, a piecewise-exponential model with two time intervals (0-3 years and ≥3 years) best characterized RFS, with no time-dependent effect of risk factors or treatment. However, for the risk of a second event after BP, a longer time interval from randomization to BP was significantly associated with a lower risk (HR 0.49; 95% CI 0.30-0.79). Similarly, in a competing-risk analysis for metastases, a longer time to BP showed a significant protective effect (sub-HR 0.41; 95% CI 0.23-0.73).

Safety and tolerability data were not reported in this analysis. The study has several limitations: these are secondary analyses, and the results represent associations rather than causal effects. The primary outcome analysis did not show a time-dependent effect of treatment. The protective effect of longer time to BP on second events should not be interpreted as a direct treatment effect.

For clinical practice, the time interval from randomization to biochemical progression appears to be a major prognostic factor for developing local or distant recurrences in patients with high-risk localized prostate cancer. Clinicians should consider this when assessing risk of progression, but these findings require confirmation in prospective studies.