Does salvage radiation therapy change the biology of recurrent prostate cancer based on PSA doubling times? Results from the SEARCH database

Objective: To investigate whether salvage radiation therapy (SRT) may promote prostate cancer (PCa) transformation to more aggressive phenotypes. To accomplish that, we identified men who underwent SRT after radical prostatectomy for PCa and failed SRT. PSA doubling time (PSADT) was used as a surrogate endpoint for cancer aggressiveness. We compared PSADT calculated before start of SRT and after SRT failure. Methods: Of 287 men in the SEARCH database since 1988 who underwent SRT, we detected 78 with SRT failure defined as PSA <0.2 ng/mL above the post-SRT nadir. Of these, 39 had PSADT available before and after SRT, which was compared using Wilcoxon's paired test with men serving as their own controls. We tested predictors of PSADT change using multivariable logistic regression. Results: There were no differences in PSADT before and after SRT (10.2 vs 12.6 months; P =.46). However, in some individual cases, large changes were observed. Only seminal vesicle invasion showed a trend towards an association with a shorter post-SRT PSADT relative to the pre-SRT PSADT (P =.13). Conclusion: Overall, the PSADT after and before SRT were statistically identical, suggesting that after SRT failure, PCa does not emerge with more aggressive biological features. Further studies are needed to identify predictors and the clinical relevance of individual PSADT changes noted in our study.