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. Androgen deprivation therapy improves overall survival when combined with radiotherapy, and such evidence is missing when the primary local treatment is radical prostatectomy. Docetaxel is associated with improved relapse-free survival in high-risk prostate cancer, but long-term follow-up is needed to assess its impact on survival. Bisphosphonates do not postpone the onset of bone metastases. © 2018 European Association of Urology
Keywords: cancer survival; overall survival; androgen; review; systemic therapy; adjuvant therapy; progression free survival; cancer therapy; gonadorelin; high risk patient; docetaxel; prostate cancer; systematic review; prostatectomy; cancer specific survival; long term care; external beam radiotherapy; androgen deprivation therapy; meta analysis; recurrence free survival; high risk; failure free survival; multimodality; metastasis free survival; human; priority journal
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
DOI: 10.1016/j.eururo.2018.07.027
PUBMED: 30286948
PROVIDER: scopus
DOI/URL:
Notes: Review -- Export Date: 1 February 2019 -- Source: Scopus
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  1. James Eastham
    422 Eastham