Background: Rezvilutamide, a novel androgen-receptor inhibitor exhibiting minimal blood-brain barrier penetration, has demonstrated robust antitumor efficacy in metastatic castration-resistant prostate cancer and high-volume, metastatic, hormone-sensitive prostate cancer, which received approval from the Chinese National Medical Products Administration in 2022. The standard management for biochemical recurrence (BCR) post-prostatectomy typically involves androgen-deprivation therapy (ADT) alone or in combination with salvage radiotherapy (SRT). This study aims to evaluate the efficacy and safety of rezvilutamide plus ADT, with or without SRT for patients with BCR post-prostatectomy. Methods: In this multi-center, open-label, two-cohort study, patients with postoperative pathology-confirmed pN0 or pNx prostate adenocarcinoma who manifested BCR subsequent to radical prostatectomy (evidenced by two successive elevated serum prostate-specific antigen [PSA] measurements between 0.2-2 ng/ml, without identifiable local or metastatic recurrence on computed tomography and bone scans) would be enrolled. Cohort 1 participants will undergo 6 months of ADT, 6 cycles of rezvilutamide (240 mg/day, spanning 28 days per cycle), and SRT. Those in Cohort 2, either declining or ineligible for SRT, will receive 12 months of ADT combined with 12 cycles of rezvilutamide. The choice of ADT regimens rests with the investigators. The primary endpoints are the 2-year biochemical progression-free survival (bPFS) rate for Cohort 1 and the 3-year bPFS rate for Cohort 2. Secondary endpoints encompass bPFS, radiographic PFS, metastasis-free survival, and rates of undetectable PSA (with PSA levels < 0.1 ng/ml). Additionally, safety profiles, overall quality of life, testosterone recovery rates post-treatment initiation, and the time to testosterone recovery post-treatment discontinuation will be appraised. The study acquired ethical approval on November 24th, 2022, and subsequently commenced recruitment. As of now, 22 out of the planned 96 patients have been enrolled. Clinical trial information: NCT05753566.