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.
European urology. 2020 Mar 04 [Epub ahead of print]
Lisa Moris, Marcus G Cumberbatch, Thomas Van den Broeck, Giorgio Gandaglia, Nicola Fossati, Brian Kelly, Raj Pal, Erik Briers, Philip Cornford, Maria De Santis, Stefano Fanti, Silke Gillessen, Jeremy P Grummet, Ann M Henry, Thomas B L Lam, Michael Lardas, Matthew Liew, Malcolm D Mason, Muhammad Imran Omar, Olivier Rouvière, Ivo G Schoots, Derya Tilki, Roderick C N van den Bergh, Theodorus H van Der Kwast, Henk G van Der Poel, Peter-Paul M Willemse, Cathy Y Yuan, Badrinath Konety, Tanya Dorff, Suneil Jain, Nicolas Mottet, Thomas Wiegel
Department of Urology, University Hospitals Leuven, Leuven, Belgium; Laboratory of Molecular Endocrinology, KU Leuven, Leuven, Belgium. Electronic address: ., Academic Urology Unit, University of Sheffield, Sheffield, UK., Department of Urology, University Hospitals Leuven, Leuven, Belgium., Unit of Urology, Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Urology, Austin Health, Heidelberg, VIC, Australia., 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., Department of Medical Oncology and Haematology, Cantonal Hospital St. Gallen, University of Bern, Bern, Switzerland; Division of Cancer Sciences, University of Manchester and The Christie, Manchester, UK., Department of Surgery, Central Clinical School, Monash University, Australia., Leeds Cancer Centre, St. James's University Hospital and University of Leeds, Leeds, UK., Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK; Academic Urology Unit, University of Aberdeen, Aberdeen, 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., 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 Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany., 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 Medical Oncology and Developmental Therapeutics, City of Hope, Duarte, CA, USA; Department of Medicine, University of Southern California (USC) Keck School of Medicine and Norris Comprehensive Cancer Center (NCCC), Los Angeles, CA, USA., Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK; Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, UK., Department of Urology, University Hospital, St. Etienne, France., Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany.