A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer

Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males. A systematic review of randomised controlled trials (RCTs) of radiotherapy and other non-pharmacological management options for localised prostate cancer was undertaken.

A search of thirteen databases was carried out until March 2014. RCTs comparing radiotherapy (brachytherapy (BT) or external beam radiotherapy (EBRT)) to other management options i.e. radical prostatectomy (RP), active surveillance, watchful waiting, high intensity focused ultrasound (HIFU), or cryotherapy; each alone or in combination, e.g. with adjuvant hormone therapy (HT), were included. Methods followed guidance by the Centre for Reviews and Dissemination and the Cochrane Collaboration. Indirect comparisons were calculated using the Bucher method.

Thirty-six randomised controlled trials (RCTs, 134 references) were included. EBRT, BT and RP were found to be effective in the management of localised prostate cancer. While higher doses of EBRT seem to be related to favourable survival-related outcomes they might, depending on technique, involve more adverse events, e.g. gastrointestinal and genitourinary toxicity. Combining EBRT with hormone therapy shows a statistically significant advantage regarding overall survival when compared to EBRT alone (Relative risk 1.21, 95% confidence interval 1.12-1.30). Aside from mixed findings regarding urinary function, BT and radical prostatectomy were comparable in terms of quality of life and biochemical progression-free survival while favouring BT regarding patient satisfaction and sexual function. There might be advantages of EBRT (with/without HT) compared to cryoablation (with/without HT). No studies on HIFU were identified.

Based on this systematic review, there is no strong evidence to support one therapy over another as EBRT, BT and RP can all be considered as effective monotherapies for localised disease with EBRT also effective for post-operative management. All treatments have unique adverse events profiles. Further large, robust RCTs which report treatment-specific and treatment combination-specific outcomes in defined prostate cancer risk groups following established reporting standards are needed. These will strengthen the evidence base for newer technologies, help reinforce current consensus guidelines and establish greater standardisation across practices.

European journal of cancer (Oxford, England : 1990) 2015 Aug 05 [Epub ahead of print]

Robert F Wolff, Steve Ryder, Alberto Bossi, Alberto Briganti, Juanita Crook, Ann Henry, Jeffrey Karnes, Louis Potters, Theo de Reijke, Nelson Stone, Marion Burckhardt, Steven Duffy, Gillian Worthy, Jos Kleijnen

Kleijnen Systematic Reviews Ltd, York, UK Electronic address: robert@systematic-reviews com , Kleijnen Systematic Reviews Ltd, York, UK , Department of Radiation Oncology, Gustave Roussy Institute, Villejuif, France , Department of Urology, Università Vita-Salute San Raffaele, Milan, Italy , University of British Columbia, Kelowna, Canada , St James's Hospital, Leeds, UK , Mayo Clinic, Rochester, USA , North Shore-LIJ Health System, Great Neck, NY, USA , Academic Medical Center, Amsterdam, The Netherlands , Mount Sinai, New York, USA , Institute of Health and Nursing Sciences, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle, Germany , Kleijnen Systematic Reviews Ltd, York, UK , Kleijnen Systematic Reviews Ltd, York, UK , Kleijnen Systematic Reviews Ltd, York, UK; Care and Public Health Research Institute (CAPHRI), Maastricht University, The Netherlands