TPS5127 Background: Standard of care for patients with prostate cancer (PC) with pelvic lymph node metastases is radiotherapy (RT) with long-term androgen deprivation therapy (ADT). In the STAMPEDE trial, James et al. assessed the role of abiraterone acetate with prednisolone (AAP) earlier in the disease for N+M0 PC patients. They showed that the addition of AAP to ADT and RT significantly improved failure-free survival (FFS) from 61% to 92.5% (ESMO 2017). Darolutamide improves survival in men with castration-refractory non-metastatic prostate cancer and in mHSPC patients with the addition of ADT plus docetaxel. We hypothesize that adding Darolutamide to ADT and RT could improve FFS for these high-risk patients. Methods: The ALADDIN study (NCT05116475) is a French, prospective, phase 3 trial that will enroll an estimated 152 patients with hormone-naive prostate cancer and pelvic lymph node metastases. Eligible patients are treatment-naive for hormonal therapy, with positive lymph node disease (upper limit defined as L4/L5 interspace) determined by conventional imaging or TEP choline or PSMA, ECOG performance status of 0 to 2, and adequate major organ function. Patients will be randomized by minimization 1:1 to receive ADT + Intensity-Modulated Image-Guided Radiation Therapy (IMRT) with darolutamide or placebo (of darolutamide). IMRT will deliver 78 Gy to the prostate, 70 Gy to the metastatic lymph nodes, and 46 Gy to the pelvic lymph node areas (2 Gy per fraction, 5 days a week) with daily CBCT imaging. ADT will be achieved with LHRH agonists or antagonists for 24 months. The darolutamide regimen will be two tablets of 300 mg orally twice daily for 24 months. The primary endpoint is failure-free survival. Secondary endpoints will be: MFS, progression-free survival, safety, overall survival, and health-related quality of life. Stratification factors are D'Amico risk group and sites. The planned sample size provides 80% power to detect a difference of 20% in FFS (60 vs 80%) at a two-sided 0.05 significance level. The study is expected to last for 7 years, of which accrual will last for 2 years. The first participant was enrolled in the study in August 2022. In total, 23 centers are participating in the ALADDIN study. The DSMB occurred on November 13 th 2023 and allowed the study to continue as planned. Clinical trial information: NCT05116475 .