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Systematic Review of Systemic Therapies and Therapeutic Combinations with Local Treatments for High-risk Localized Prostate Cancer

Tijdschriftbijdrage - Tijdschriftartikel

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.
Tijdschrift: European Urology
ISSN: 0302-2838
Issue: 1
Volume: 75
Pagina's: 44 - 60
Jaar van publicatie:2019
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:10
CSS-citation score:3
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Open