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Eur Urol. 2019 Jan;75(1):44-60. doi: 10.1016/j.eururo.2018.07.027. Epub 2018 Oct 2.

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

Author information

1
Department of Urology, University Hospitals Leuven, Leuven, Belgium; Nuclear Medicine & Molecular Imaging, KU Leuven, Leuven, Belgium. Electronic address: lorenzo.tosco@uzleuven.be.
2
Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
3
Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA, USA.
4
Urology Service at the Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
5
Department of Oncology in the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
6
The Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
7
Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium.
8
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
9
Department of Urology, Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal, Quebec, Canada.
10
Dana-Farber Cancer Institute, Boston, MA, USA.
11
Institut Gustave Roussy, University of Paris Sud, Villejuif, France.

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.

KEYWORDS:

High risk; Multimodality; Prostate cancer; Systematic review; Systemic therapy

PMID:
30286948
DOI:
10.1016/j.eururo.2018.07.027
[Indexed for MEDLINE]

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