TIDE-PC Phase 2 Trial Will Test Testosterone-Guided ADT De-Escalation in Metastatic Prostate Cancer

A newly registered phase 2 clinical trial, TIDE-PC, will investigate whether men with metastatic hormone-sensitive prostate cancer (mHSPC) who have maintained a prolonged response to treatment can safely receive fewer androgen deprivation therapy (ADT) injections while continuing androgen receptor pathway inhibitors (ARPIs).

Unlike traditional intermittent ADT approaches, which commonly interrupt hormonal treatment according to PSA response and subsequently restart it following biochemical progression, TIDE-PC will use serum testosterone levels to guide ADT administration. Patients will continue their ARPI throughout the study, potentially maintaining additional suppression of androgen receptor signaling while reducing the frequency of GnRH agonist injections.

The single-arm, open-label study plans to enroll 56 men who have received continuous ADT combined with abiraterone, enzalutamide, apalutamide, or darolutamide for at least 18 months. Eligible participants must have stable PSA levels below 4 ng/mL and castrate testosterone below 50 ng/dL. Every three months, investigators will measure testosterone and PSA. Scheduled GnRH agonist injections will be withheld while testosterone remains below the castration threshold and resumed when testosterone reaches or exceeds 50 ng/dL. ARPI treatment will continue without interruption.

The primary endpoint is the cumulative incidence of castration resistance, clinical relapse, or death over 18 months. Secondary endpoints include PSA progression, overall survival, the number of ADT injections avoided, testosterone recovery, and patient-reported quality of life, including hot flash-related interference. PSA increases may also trigger a return to continuous ADT.

The rationale is that testosterone suppression can persist after GnRH agonist administration is interrupted, particularly following prolonged hormonal treatment. Consequently, some patients may remain adequately androgen-deprived without receiving every scheduled injection. However, reducing injection frequency does not necessarily mean reversing the physiological effects of castration, particularly if testosterone remains suppressed.

Clinical trial.