Background: The development of androgen receptor pathway inhibitors (ARPI) - abiraterone acetate, apalutamide, darolutamide and enzalutamide - has profoundly reshaped the management of metastatic hormone naïve prostate cancer (mHNPC). Seven trials demonstrated that combining these drugs with androgen deprivation therapy (ADT) reduces the risk of death by 20-40%, delays further treatment, and improves health-related quality of life (HR-QoL). These trials, however, suffer from two critical limitations: treatment duration and patient selection. Treatment usually continues until biochemical, radiological, or clinical progression, sometimes many years after drug initiation, exposing patients to chronic side effects affecting their QoL. Furthermore, registration trials include those not representative of the general population. Several sub-analyses of the registration trials demonstrated that patients achieving a PSA ≤0.2 ng/ml have prolonged overall survival (OS). In this study, we hypothesized that patients reaching PSA ≤ 0.2 ng/ml may benefit from treatment interruption without compromising OS. Methods: The primary goal of this academic-led, open-label, multicenter, pragmatic, randomized phase III study is to investigate whether intermittent maximum androgen blockade (iMAB) can be safely administered to mHNPC patients who reached a PSA ≤ 0.2 ng/mL at 6-12 months of continuous treatment (cMAB), as compared to continuing cMAB. Recommendations for restart include increasing clinical or radiological progression or PSA to ≥ 50% of diagnostic PSA with a maximum of 5 ng/mL.This will be demonstrated through the following co-primary objectives: 1) The proportion of patients who do not need to restart their MAB within one year of interruption is not less than 70%. 2) OS using an iMAB regimen at three years is non-inferior to continuous treatment. Secondary objectives include toxicity comparisons, HR-QoL (physical functioning, role functioning and fatigue scales of EORTC QLQ-C30, sexual activity scale of EORTC QLQ PR25), and assessing the impact on treatment resources of using an intermittent schedule. The study will include 1600 patients treated by cMAB for mHNPC for 6-12 months presenting with a PSA ≤ 0.2 ng/mL. Patients may have received docetaxel and radiotherapy as part of standard treatment. The PRECIS-2 (Pragmatic-Explanatory Continuum Indicator Summary) will be used to evaluate the study as a pragmatic trial. Clinical trial information: NCT05974774.