Is The Phoenix Criterion Of Biochemical Failure (BF) In Men Treated With Low-Dose Rate Prostate Brachytherapy Appropriate?

Abstract

PSA kinetics post-brachytherapy are not well described. Our aim was to validate the Phoenix criterion (PC nadir+2) for BF in men treated with prostate brachytherapy without ADT, a definition initially established based on retrospective analysis of external beam radiotherapy data. Our dataset consisted of 9,219 patients from 3 countries who received l-125 or Pd-103 low dose rate prostate brachytherapy without ADT. First, to compare the performance of the different PC definitions, we applied ROC analysis to test the significance of the difference between AUC for PC nadir+2 and that for alternative PSA failure definitions (PSA> = X after Y years of follow up, where X = 1.5-4.0 and Y = 0-1.5). Second, the Mann-Whitney rank-sum test was applied to test for any difference between the time to PC nadir+2 failure or time to alternative PSA failure definition, and time to clinical failure in cases where both a clinical failure and a PSA-predicted failure occurred. 4,169 (45.2%), 4,665 (50.6%), and 385 (4.2%) of the patients without ADT were respectively low risk, intermediate risk, and high risk. Median follow up was 5.3 years. Alternative definitions of BF were not significantly superior to the PC nadir+2 (all p-values > 0.05). The times to clinical failure after biochemical failure were slightly but not significantly shorter for the PC nadir+2 definition (1.6 y) than for those using the best-performing of the alternative definitions: PSA> = 3 after 0.5 years follow up (1.84 y). Findings from an international cohort validate use of the nadir+2 PC for BF in men receiving definitive low dose rate prostate brachytherapy without androgen deprivation therapy for prostate cancer.