Quantifying the Impact of Biochemical Recurrence After Radical Prostatectomy on Overall Mortality by Years of Life Lost: Results from the SEARCH Database

The impact of biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP) on overall mortality (OM) remains uncertain. Specifically, there are no patient-centered quantitative data on the impact of BCR on life expectancy. We compared OM and remaining lifetime between groups of patients with and without BCR after RP.

We identified 7820 participants who underwent RP, of whom 2846 (36%) had BCR. Associations between BCR and OM were assessed via Cox models with BCR as a time-dependent covariate. Years of life lost (YLL) associated with BCR (difference in remaining lifetime between the BCR and no-BCR groups) was estimated via Poisson regression. In secondary analyses the BCR group was stratified by prostate-specific antigen doubling time (PSADT).

BCR was associated with modestly higher risk of OM on multivariable analysis (hazard ratio 1.29; p < 0.001). On PSADT stratification, only the BCR subgroups with PSADT of <3 mo or 3-8.9 mo had significantly higher OM risk in comparison to the group without BCR on multivariable analysis (both p < 0.001). At the median time to recurrence, remaining lifetime was 16.7 yr for the group without BCR and 15.3 yr for the BCR group (1.4 YLL). YLL stratified by PSADT subgroup was 6.8 yr for PSADT <3 mo, 2.8 yr for PSADT 3-8.9 mo, and <1 yr for PSADT >9 mo. Early salvage radiation and/or hormonal therapy was more common in the BCR subgroup with PSADT <9 mo (p < 0.001).

BCR after RP was significantly associated with a modest increased in the risk of OM and 1.4 YLL. In the BCR subgroup with PSADT <9 mo, the OM risk was dramatically higher, with 3-7 YLL, despite more frequent and earlier secondary treatment. These results quantify YLL associated with high-risk BCR for the first time, and can support patient-centered discussion and consideration of intensified salvage treatment validated in recent clinical trials and regimens recommended in clinical practice guidelines.