Impact of Sequencing of Androgen Suppression and Radiotherapy on Testosterone Recovery in Localized Prostate Cancer.

Abstract Purpose We performed a secondary analysis of a phase III randomized trial to determine the influence of sequencing of radiotherapy and ADT on post-treatment testosterone recovery and implications of testosterone recovery on subsequent relapse. Methodology Localized prostate cancer patients with Gleason score ≤7, clinical stage T1b-T3a, and prostate-specific antigen 10.5 nmol/L in patients with baseline ≥10.5 nmol/L or to baseline level in patients with baseline 1.7 nmol/L) and FTR was compared between the arms using a truncation time point of 36 months. Results The adjusted difference in RMST to supra-castrate testosterone between the CAHT and NHT arm was 1.5 months (95% CI: 0.5 to 2.5, p=0.005). No difference was noted in RMST to FTR between the arms (18.7 versus 18.5 months, adjusted difference: 0.5, 95% CI: -1.4 to 2.4, p=0.61). There was no evidence of heterogeneity of treatment effect (interaction p=0.76) on risk of relapse over subgroups stratified by testosterone recovery to supra-castrate level at 15 months after start of ADT. Based on a multi-state Markov model, no independent effect of time to FTR on risk of subsequent relapse was observed (adjusted hazard ratio: 1.02, 95%CI: 0.96-1.08). Conclusion Patients should be counselled that after treatment with prostate radiotherapy and 6 months of ADT, it needs on average an additional 12 months for the FTR to occur. This is independent of the sequencing of ADT and radiotherapy. Furthermore, recovery of testosterone does not appear to impact the risk of subsequent relapse.