The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.
To perform a systematic review to determine the benefits and harms of EBRT-BT.
Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs).
Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs.
EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control.
We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.
European urology oncology. 2023 Dec 26 [Epub ahead of print]
Finbar Slevin, Fabio Zattoni, Enrico Checcucci, Marcus G K Cumberbatch, Antonio Nacchia, Philip Cornford, Erik Briers, Gert De Meerleer, Maria De Santis, Daniel Eberli, Giorgio Gandaglia, Silke Gillessen, Nikolaos Grivas, Matthew Liew, Estefania E Linares Espinós, Jan Oldenburg, Daniela E Oprea-Lager, Guillaume Ploussard, Olivier Rouvière, Ivo G Schoots, Emma Jane Smith, Johan Stranne, Derya Tilki, Catrin Tudur Smith, Roderick C N Van Den Bergh, Inge M Van Oort, Thomas Wiegel, Cathy Y Yuan, Thomas Van den Broeck, Ann M Henry
University of Leeds, Leeds, UK; Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK. Electronic address: ., Department Surgery, Oncology and Gastroenterology, Urologic Unit, University of Padova, Padova, Italy., Division of Urology, Department of Oncology, School of Medicine, San Luigi Hospital, University of Turin, Turin, Italy., Academic Urology Unit, University of Sheffield, Sheffield, UK., Urology Department, IRCCS CROB, Rionero in Vulture, Italy., Department of Urology, Liverpool University Hospitals NHS Trust, Liverpool, UK., Hasselt, Belgium., Department of Radiotherapy, University Hospitals Leuven, Leuven, Belgium., Department of Urology, Charité Universitätsmedizin, Berlin, Germany; Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Department of Urology, San Raffaele Hospital, Milan, Italy., Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland., Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Urology, Wrightington, Wigan and Leigh NHS Foundation Trust, Wigan, UK., Department of Urology, Hospital Universitario La Paz, Madrid, Spain., Department of Oncology, Akershus University Hospital, Lørenskog, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway., Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Department of Urology, La Croix du Sud Hospital, Toulouse, France., Hospices Civils de Lyon, Department of Urinary and Vascular Imaging, Hôpital Edouard Herriot, Lyon, France., Department of Radiology & Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands., European Association of Urology Guidelines Office, Arnhem, The Netherlands., Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Koc University Hospital, Istanbul, Turkey., Department of Health Data Science, University of Liverpool, Liverpool, UK., Department of Urology, St. Antonius Hospital, Utrecht, The Netherlands., Radboud University Medical Center, Department of Urology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands., University Hospital Ulm, Ulm, Germany., Department of Medicine, Health Science Centre, McMaster University, Hamilton, Ontario, Canada., GZA Hospitals, Antwerp, Belgium., University of Leeds, Leeds, UK; Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.