Association of PSA kinetics after testosterone recovery with subsequent recurrence: secondary analysis of a phase III randomized controlled trial

Purpose After cessation of androgen deprivation therapy (ADT), testosterone gradually recovers to supracastrate levels (> 50 ng/dL). After this, rises in prostate-specific antigen (PSA) are often seen. However, it remains unknown whether early PSA kinetics after testosterone recovery are associated with subsequent biochemical recurrence (BCR). Methods We performed a secondary analysis of a phase III randomized controlled trial in which newly diagnosed localized prostate cancer patients were randomly allocated to ADT for 6 months starting 4 months prior to or simultaneously with prostate RT. We calculated the PSA doubling time (PSADT) based on PSA values up to 18 months after supracastrate testosterone recovery. Competing risk regression was used to evaluate the association of PSADT with relative incidence of BCR, considering deaths as competing events. Results Overall, 313 patients were eligible. Median PSADT was 8 months. Cumulative incidence of BCR at 10 years from supracastrate testosterone recovery was 19% and 11% in patients with PSADT < 8 months and ≥ 8 months ( p = 0.03). Compared to patients with PSADT of < 4 months, patients with higher PSADT (sHR for PSADT 4 to < 8 months: 0.36 [95% CI 0.16–0.82]; 8 to < 12 months: 0.26 [0.08–0.91]; ≥ 12 months: 0.20 [0.07–0.56]) had lower risk of relative incidence of BCR. Conclusions Early PSA kinetics, within 18 months of recovery of testosterone to a supracastrate level, can predict for subsequent BCR. Taking account of early changes in PSA after testosterone recovery may allow for recognition of potential failures earlier in the disease course and thereby permit superior personalization of treatment.