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


Journal

European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719

Informations de publication

Date de publication:
06 2020
Historique:
received: 22 06 2019
accepted: 29 11 2019
pubmed: 24 12 2019
medline: 22 6 2021
entrez: 24 12 2019
Statut: ppublish

Résumé

No standard therapy has been established for localised prostate cancer patients with prostate-specific antigen (PSA) failure after radical prostatectomy (RP). To determine whether radiotherapy ± hormone therapy is superior to hormone therapy alone in such patients. 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. The primary endpoint was time to treatment failure (TTF) of BCL. 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. Initial SRT prolongs TTF of BCL in patients with post-RP PSA failure, indicating that SRT ± SHT is more beneficial than SHT alone. Patients who have prostate-specific antigen failure after radical prostatectomy benefit from salvage radiation therapy prior to salvage hormone therapy.

Sections du résumé

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.

Identifiants

pubmed: 31866092
pii: S0302-2838(19)30896-6
doi: 10.1016/j.eururo.2019.11.023
pii:
doi:

Substances chimiques

Anilides 0
Antineoplastic Agents 0
Nitriles 0
Tosyl Compounds 0
Gonadotropin-Releasing Hormone 33515-09-2
bicalutamide A0Z3NAU9DP
Prostate-Specific Antigen EC 3.4.21.77

Types de publication

Clinical Trial, Phase III Comparative Study Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

689-698

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2019. Published by Elsevier B.V.

Auteurs

Akira Yokomizo (A)

Department of Urology, Harasanshin Hospital, Fukuoka, Japan.

Masashi Wakabayashi (M)

Japan Clinical Oncology Group Data Centre/Operations Office, National Cancer Centre Hospital, Tokyo, Japan.

Takefumi Satoh (T)

Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan.

Katsuyoshi Hashine (K)

Department of Urology, National Hospital Organization Shikoku Cancer Centre, Ehime, Japan.

Takahiro Inoue (T)

Department of Urology, Kyoto University Hospital, Kyoto, Japan.

Kiyohide Fujimoto (K)

Department of Urology, Nara Medical University, Nara, Japan.

Shin Egawa (S)

Department of Urology, Jikei University Hospital, Tokyo, Japan.

Tomonori Habuchi (T)

Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.

Kiyotaka Kawashima (K)

Department of Urology, Tochigi Cancer Centre, Tochigi, Japan.

Osamu Ishizuka (O)

Department of Urology, Shinshu University School of Medicine, Nagano, Japan.

Nobuo Shinohara (N)

Department of Renal and Genitourinary Surgery, Hokkaido University Hospital, Hokkaido, Japan.

Mikio Sugimoto (M)

Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Yasushi Yoshino (Y)

Department of Urology, Nagoya University School of Medicine, Nagoya, Japan.

Keiji Nihei (K)

Division of Radiation Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital, Bunkyo City, Japan.

Haruhiko Fukuda (H)

Japan Clinical Oncology Group Data Centre/Operations Office, National Cancer Centre Hospital, Tokyo, Japan.

Ken-Ichi Tobisu (KI)

Tokyo Metropolitan Cancer and Infectious disease Centre, Komagome Hospital, Bunkyo City, Japan.

Yoshiyuki Kakehi (Y)

Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Seiji Naito (S)

Department of Urology, Harasanshin Hospital, Fukuoka, Japan. Electronic address: naito@harasanshin.or.jp.

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Classifications MeSH