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Title: Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review.
Austin Authors: Moris, Lisa;Cumberbatch, Marcus G;Van den Broeck, Thomas;Gandaglia, Giorgio;Fossati, Nicola;Kelly, Brian;Pal, Raj;Briers, Erik;Cornford, Philip;De Santis, Maria;Fanti, Stefano;Gillessen, Silke;Grummet, Jeremy P;Henry, Ann M;Lam, Thomas B L;Lardas, Michael;Liew, Matthew;Mason, Malcolm D;Omar, Muhammad Imran;Rouvière, Olivier;Schoots, Ivo G;Tilki, Derya;van den Bergh, Roderick C N;van Der Kwast, Theodorus H;van Der Poel, Henk G;Willemse, Peter-Paul M;Yuan, Cathy Y;Konety, Badrinath;Dorff, Tanya;Jain, Suneil;Mottet, Nicolas;Wiegel, Thomas
Affiliation: Academic Urology Unit, University of Aberdeen, Aberdeen, UK
Laboratory of Molecular Endocrinology, KU Leuven, Leuven, Belgium
Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK
Department of Medical Oncology and Developmental Therapeutics, City of Hope, Duarte, CA, USA
Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Division of Cancer Sciences, University of Manchester and The Christie, Manchester, UK
Department of Medical Oncology and Haematology, Cantonal Hospital St. Gallen, University of Bern, Bern, Switzerland
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK
Department of Urology, Austin Health, Heidelberg, Victoria, Australia
Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, UK
Hospices Civils de Lyon, Department of Urinary and Vascular Imaging, Hôpital Edouard Herriot, Lyon, France
Faculté de Médecine Lyon Est, Université Lyon 1, Université de Lyon, Lyon, France
Department of Medicine, University of Southern California (USC) Keck School of Medicine and Norris Comprehensive Cancer Center (NCCC), Los Angeles, CA, USA
Academic Urology Unit, University of Sheffield, Sheffield, UK
Department of Surgery, Central Clinical School, Monash University, Australia
Department of Urology, University Hospitals Leuven, Leuven, Belgium
Unit of Urology, Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
Bristol Urological Institute, Southmead Hospital, Bristol, UK
Patient Advocate, Hasselt, Belgium
Royal Liverpool and Broadgreen Hospitals NHS Trust, Liverpool, UK
Department of Urology, Charité University Hospital, Berlin, Germany
Department of Nuclear Medicine, Policlinico S. Orsola, University of Bologna, Italy
Leeds Cancer Centre, St. James's University Hospital and University of Leeds, Leeds, UK
Department of Urology, Leto Hospital, Athens, Greece
Department of Urology, Wrightington, Wigan and Leigh NHS Foundation Trust, Wigan, UK
Division of Cancer & Genetics, School of Medicine Cardiff University, Velindre Cancer Centre, Cardiff, UK
Academic Urology Unit, University of Aberdeen, Aberdeen, UK
Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Department of Urology, Antonius Hospital, Utrecht, The Netherlands
Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands
Department of Oncological Urology, University Medical Center, Utrecht Cancer Center, Utrecht, The Netherlands
Department of Medicine, Health Science Centre, McMaster University, Hamilton, ON, Canada
University of Minnesota, Minneapolis, MN, USA
Department of Urology, University Hospital, St. Etienne, France
Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany
Issue Date: May-2020
Date: 2020-03-04
Publication information: European Urology 2020; 77(5): 614-627
Abstract: The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 yr of follow-up. Secondary oncological outcomes are PCa-specific mortality, overall mortality, biochemical recurrence, and need for salvage treatment with ≥5 yr of follow-up. Nononcological outcomes are quality of life (QoL), functional outcomes, and treatment-related side effects reported. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and nonrandomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (International Society of Urologic Pathologists [ISUP] grade 4-5 [Gleason score {GS} 8-10] or prostate-specific antigen [PSA] >20 ng/ml or ≥ cT2c) and/or locally advanced PCa (any PSA, cT3-4 or cN+, any ISUP grade/GS) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT), or multimodality treatment combining any of the local treatments above (±any systemic treatment). Risk of bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed. Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance, and detection bias, and low RoB for correction of initial PSA and biopsy GS. When comparing RP with EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (postoperative) RT and/or androgen deprivation therapy (ADT), respectively. High levels of evidence exist for EBRT treatment, with several randomized clinical trials showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose, but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in genitourinary toxicity and sexual dysfunction, and EBRT in bowel problems. Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, EBRT + BT can also be offered despite more grade 3 toxicity. Interestingly, for selected patients, for example, those with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will most likely be in the context a multimodality treatment plan. In particular, if radiation is used, the combination of local with systemic treatment provides the best outcome, provided the patient is fit enough to receive both. Until the results of the SPCG15 trial are known, the optimal local treatment remains a matter of debate. Patients should at all times be fully informed about all available options, and the likelihood of a multimodal approach including the potential side effects of both local and systemic treatment. We reviewed the literature to see whether the evidence from clinical studies would tell us the best way of curing men with aggressive prostate cancer that had not spread to other parts of the body such as lymph glands or bones. Based on the results of this systematic review, there is good evidence that both surgery and radiation therapy are good treatment options, in terms of prolonging life and preserving quality of life, provided they are combined with other treatments. In the case of surgery this means including radiotherapy (RT), and in the case of RT this means either hormonal therapy or combined RT and brachytherapy.
DOI: 10.1016/j.eururo.2020.01.033
Journal: European urology
PubMed URL: 32146018
Type: Journal Article
Subjects: Brachytherapy
External beam radiotherapy
Locally advanced
Modality treatment
Primary therapy
Prostate cancer
Radical prostatectomy
Systematic review
Systemic treatment
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