Intermittent androgen deprivation therapy for biochemical recurrence or prostate-specific antigen (PSA) persistence after radical prostatectomy: efficacy and prognostic factors

Background: The optimal protocol for intermittent androgen deprivation therapy (IAD) in managing biochemical recurrence (BCR) and persistent prostate-specific antigen (PSA) levels after radical prostatectomy (RP) remains undefined. This study aimed to introduce a novel IAD protocol, conduct an initial assessment of the protocol’s effectiveness in real-world settings, and develop a risk-based model to identify patients most likely to benefit from this approach. Methods: This study included 175 post-RP patients receiving IAD, with a median follow-up of 44.77 months [interquartile range (IQR), 31.87–69.50 months] post-androgen deprivation therapy (ADT). The IAD protocol used a PSA threshold of 0.2 ng/mL to define progression during the first intermittent phase. Key clinical and pathological parameters, including PSA kinetics and testosterone levels, were analyzed. Cox regression assessed the duration of the first intermittent phase, while logistic regression analyses identified factors associated with the efficacy of ADT in the second treatment phase. Nomograms were developed for clinical applications. Results: Cox regression analysis revealed that the duration of the first intermittent phase was significantly associated with castration-resistant prostate cancer (CRPC)-free survival. Pathological Gleason grade group 5 (GGG 5) was a risk factor for a shorter first intermittent phase, while PSA doubling time (PSADT) ≥3.32 months and testosterone doubling time (TDT) ≥5.03 months were protective factors. Logistic regression identified combined metformin use, testosterone recovery to normal levels during the first intermittent phase, and a PSA response rate ≥90% after the first luteinizing hormone-releasing hormone (LHRH) injection in the first treatment cycle as protective factors against a PSA response rate < 90% during salvage ADT in the second treatment phase [area under the curve (AUC) =0.84]. Conclusions: The duration of the first intermittent phase was a significant predictor of CRPC-free survival. PSADT, TDT, and pathological GGG 5 were independent predictors of this duration. Furthermore, combined metformin use appeared to preserve ADT sensitivity in patients with PSA progression during the first intermittent phase.