Systematic review of systemic therapies and therapeutic combinations with local treatments for high-risk localized prostate cancer Journal Article


Authors: Tosco, L.; Briganti, A.; D'Amico, A. V.; Eastham, J.; Eisenberger, M.; Gleave, M.; Haustermans, K.; Logothetis, C. J.; Saad, F.; Sweeney, C.; Taplin, M. E.; Fizazi, K.
Article Title: Systematic review of systemic therapies and therapeutic combinations with local treatments for high-risk localized prostate cancer
Abstract: Context: Systemic therapies, combined with local treatment for high-risk prostate cancer, are recommended by the international guidelines for specific subgroups of patients; however, for many of the clinical scenarios, it remains a research field. Objective: To perform a systematic review, and describe current evidence and perspectives about the multimodal treatment of high-risk prostate cancer. Evidence acquisition: We performed a systematic review of PubMED, Embase, Cochrane Library, European Society of Medical Oncology/American Society of Clinical Oncology Annual proceedings, and clinicalTrial.gov between January 2010 and February 2018 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Evidence synthesis: Seventy-seven prospective trials were identified. According to multiple randomized trials, combining androgen deprivation therapy (ADT) with external-beam radiotherapy (EBRT) outperforms EBRT alone for both relapse-free and overall survival. Neoadjuvant ADT did not show significant improvement compared with prostatectomy alone. The role of adjuvant ADT after prostatectomy in patients with high-risk disease is still debated, with lack of data from phase 3 trials in pN0 patients. Novel androgen pathway inhibitors have been tested only in early-phase trials in addition to primary treatment. GETUG 12, RTOG 0521, and nonmetastatic subgroup of the STAMPEDE trial showed improved relapse-free survival for docetaxel in patients treated with EBRT plus ADT, although mature metastasis-free survival data are still pending. Both the SPCG-12 and the VACSP#553 trial showed no improvement in relapse-free survival for adjuvant docetaxel after prostatectomy. Conclusions: In contrast to the clearly demonstrated survival benefits of long-term adjuvant ADT when used with EBRT, its role after prostatectomy remains unclear especially in pN0 patients. Adding docetaxel to EBRT-ADT improves relapse-free survival, with immature results on overall survival. Novel androgen receptor pathway inhibitors are currently being tested in the neoadjuvant and adjuvant setting. Patient summary: Treatment of high-risk prostate cancer is based on a multimodality approach that includes systemic treatments. The best treatment or therapy combination remains to be defined. (c) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Keywords: prostate cancer; systematic review; radical prostatectomy; therapy; radiation-therapy; phase-iii trial; randomized-trial; androgen-deprivation therapy; oncology-group; high risk; 10-year follow-up; systemic; estramustine phosphate; multimodality; long-term update; chemohormonal
Journal Title: European Urology
Volume: 75
Issue: 1
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2019-01-01
Start Page: 44
End Page: 60
Language: English
ACCESSION: WOS:000452876600012
DOI: 10.1016/j.eururo.2018.07.027
PROVIDER: wos
PUBMED: 30286948
Notes: Review -- Source: Wos
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MSK Authors
  1. James Eastham
    420 Eastham