Salvage Radiotherapy Versus Hormone Therapy for Prostate-specific Antigen Failure After Radical Prostatectomy: A Randomised, Multicentre, Open-label, Phase 3 Trial (JCOG0401)

Eur Urol. 2020 Jun;77(6):689-698. doi: 10.1016/j.eururo.2019.11.023. Epub 2019 Dec 19.


Background: No standard therapy has been established for localised prostate cancer patients with prostate-specific antigen (PSA) failure after radical prostatectomy (RP).

Objective: To determine whether radiotherapy ± hormone therapy is superior to hormone therapy alone in such patients.

Design, setting, and participants: This study is a multicentre, randomised, open-label, phase 3 trial. Patients with localised prostate cancer whose PSA concentrations had decreased to <0.1 ng/ml after RP, and then increased to 0.4-1.0 ng/ml, were randomised to the salvage hormone therapy (SHT) group (80 mg bicalutamide [BCL] followed by luteinising hormone-releasing hormone agonist in case of BCL failure) or the salvage radiation therapy (SRT) ± SHT group (64.8 Gy of SRT followed by the same regimen as in the SHT group in case of SRT failure). From May 2004 to May 2011, 210 patients (105 in each arm) were registered, with the median follow-up being 5.5 yr.

Outcome measurements and statistical analysis: The primary endpoint was time to treatment failure (TTF) of BCL.

Results and limitations: TTF of BCL was significantly longer in the SRT ± SHT group (8.6 yr) than in the SHT group (5.6 yr; hazard ratio 0.56, 90% confidence interval [0.40-0.77]; one-sided p = 0.001). Thirty-two of 102 patients (31%) in the SRT ± SHT group did not have SRT treatment failure. However, clinical relapse-free survival and overall survival did not differ between the arms. The most frequent grade 3-4 adverse event was erectile dysfunction (83 patients [80%] in the SHT group vs. 76 [74%] in the SRT ± SHT group). Limitations include the short follow-up periods and surrogate endpoint setting to allow definitive conclusions.

Conclusions: Initial SRT prolongs TTF of BCL in patients with post-RP PSA failure, indicating that SRT ± SHT is more beneficial than SHT alone.

Patient summary: Patients who have prostate-specific antigen failure after radical prostatectomy benefit from salvage radiation therapy prior to salvage hormone therapy.

Keywords: Prostate-specific antigen failure; Radical prostatectomy; Salvage therapy.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anilides / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Gonadotropin-Releasing Hormone / agonists*
  • Humans
  • Male
  • Nitriles / therapeutic use*
  • Prostate-Specific Antigen / blood
  • Prostatectomy / methods
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / radiotherapy*
  • Prostatic Neoplasms / surgery
  • Salvage Therapy
  • Tosyl Compounds / therapeutic use*
  • Treatment Failure


  • Anilides
  • Antineoplastic Agents
  • Nitriles
  • Tosyl Compounds
  • Gonadotropin-Releasing Hormone
  • bicalutamide
  • Prostate-Specific Antigen