Objective The aim of the study was to evaluate the efficiency of salvage treatments for prostate specific antigen (PSA) relapse of cT3N0M0 prostatic adenocarcinoma (PCa) after radical prostatectomy (RP) combined with neoadjuvant androgen deprivation (ADT).Methods A total of 332 patients with cT3N0M0 PCa were enrolled in the prospective study and received RP and pelvic lymph node dissection with neoadjuvant ADT for 3 months. All patients with PSA relapse were treated with salvage external beam radiation therapy (RT) and ADT for 6 months. Results The 5-year postoperative PSA relapse rate was 40.96％ (136/332). The patients have been divided into the PSA relapse and PSA relapse-free groups in order to compare patient characteristics. The ratio of patients with Gleason score ≥ 8 and positive surgical margin in the PSA relapse group were significantly higher than those of in the PSA relapse-free group (P = 0.01). The mean duration between the start of operative treatment and PSA relapse was 31 months. Salvage treatment to all 136 PSA relapse patients led to favorable outcomes. PSA relapse was not observed after salvage treatment by the end of follow-up. The 5-year overall survival rates of the PSA relapse and PSA relapse-free groups were 94.9％ and 93.9％, respectively. Conclusion In pursuit of curative treatment, our study showed that RP combined with neoadjuvant ADT is an aggressive multimodality strategy associated with lower PSA relapse and better survival outcomes for stage cT3N0M0 PCa patients. Patients with PSA relapse after RP may benefit from early aggressive salvage RT combined with short-term ADT.