Lead-time bias does not falsify the efficacy of early salvage radiotherapy for recurrent prostate cancer

Background: In prostate cancer (PCa) recurring after radical prostatectomy (RP), salvage radiotherapy (SRT) is recommended to be given at PSA <0.5 ng/ml. It has been speculated, that the advantage from early SRT is mainly caused by lead-time bias: Calculating from time of SRT, earlier treatment would per-se result in longer time to event/censoring compared with later treatment, but not extend the interval from RP to post-SRT failure. Methods: In 603 consecutive PCa patients receiving SRT between 1997 and 2017, we compared outcomes, calculating from time of irradiation vs. time of surgery. Results: In multivariable analysis, tumor stage pT3-4, pathological Gleason score GS <= 6 vs. GS 7 vs. GS >= 8, post-RP PSA persistence (nadir >= 0.1 ng/ml), and the pre-SRT PSA (continuous or with cutoff 0.4 ng/ml) were significant risk-factors for biochemical progression (BCR) and progression-free survival (PFS) post-SRT and post-RP. A pre-SRT PSA <0.4 ng/ml was a significant discriminator for Kaplan-Meier rates of BCR and PFS. The Cox model for overall survival (OS) included age at RP (continuous), pT2 vs. pT3-4, and pre-SRT PSA (continuous) as significant predictors. However, no significant cutoff for the pre-SRT PSA could be identified to differentiate Kaplan-Meier estimates of OS, possibly because there were too few events, as 88% of the patients were still alive at last follow-up. Conclusions: The pre-SRT PSA has a significant impact on BCR, PFS and potentially on OS, calculating either from RP or from SRT to event/censoring, respectively. This contradicts the hypothesis of lead-time bias falsifying the advantage from early SRT. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

In prostate cancer patients, a pre-SRT PSA <0.4 ng/ml is a significant predictor for biochemical progression (BCR), progression-free survival (PFS), and overall survival (OS), contradicting the hypothesis that the advantage of early salvage radiotherapy (SRT) is mainly due to lead-time bias.