A Systematic Review of Focal Ablative Therapy for Clinically Localised Prostate Cancer in Comparison with Standard Management Options: Limitations of the Available Evidence and Recommendations for Clinical Practice and Further Research.

The clinical effectiveness of focal therapy (FT) for localised prostate cancer (PCa) remains controversial.

To analyse the evidence base for primary FT for localised PCa via a systematic review (SR) to formulate clinical practice recommendations.

A protocol-driven, PRISMA-adhering SR comparing primary FT (sub-total, focal, hemi-gland, or partial ablation) versus standard options (active surveillance [AS], radical prostatectomy [RP], or external beam radiotherapy [EBRT]) was undertaken. Only comparative studies with ≥50 patients per arm were included. Primary outcomes included oncological, functional, and quality-of-life outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Eligible SRs were reviewed and appraised (AMSTAR) and ongoing prospective comparative studies were summarised.

Out of 1119 articles identified, four primary studies (1 randomised controlled trial [RCT] and 3 retrospective studies) recruiting 3961 patients and ten eligible SRs were identified. Only qualitative synthesis was possible owing to clinical heterogeneity. Overall, RoB and confounding were moderate to high. An RCT comparing vascular-targeted focal photodynamic therapy (PDT) with AS found a significantly lower rate of treatment failure at 2 yr with PDT. There were no differences in functional outcomes, although PDT was associated with worse transient adverse events. However, the external validity of the study was contentious. A retrospective study comparing focal HIFU with robotic RP found no significant differences in treatment failure at 3 yr, with focal HIFU having better continence and erectile function recovery. Two retrospective cohort studies using Surveillance, Epidemiology and End Results data compared focal laser ablation (FLA) against RP and EBRT, reporting significantly worse oncological outcomes for FLA. The overall data quality and applicability of the primary studies were limited because of clinical heterogeneity, RoB and confounding, lack of long-term data, inappropriate outcome measures, and poor external validity. Virtually all the SRs identified concluded that there was insufficient high-certainty evidence to make definitive conclusions regarding the clinical effectiveness of FT, with the majority of SRs judged to have a low or critically low confidence rating. Eight ongoing prospective comparative studies were identified. Ways of improving the evidence base are discussed.

The certainty of the evidence regarding the comparative effectiveness of FT as a primary treatment for localised PCa was low, with significant uncertainties. Until higher-certainty evidence emerges from robust prospective comparative studies measuring clinically meaningful outcomes at long-term time points, FT should ideally be performed within clinical trials or well-designed prospective cohort studies.

We examined the literature to determine the effectiveness of prostate-targeted treatment compared with standard treatments for untreated localised prostate cancer. There was no strong evidence showing that focal treatment compares favourably with standard treatments; consequently, focal treatment is not recommended for routine standard practice.

European urology oncology. 2021 Jan 07 [Epub ahead of print]

Anthony S Bates, Jennifer Ayers, Nikolaos Kostakopoulos, Thomas Lumsden, Ivo G Schoots, Peter-Paul M Willemse, Yuhong Yuan, Roderick C N van den Bergh, Jeremy P Grummet, Henk G van der Poel, Olivier Rouvière, Lisa Moris, Marcus G Cumberbatch, Michael Lardas, Matthew Liew, Thomas Van den Broeck, Giorgio Gandaglia, Nicola Fossati, Erik Briers, Maria De Santis, Stefano Fanti, Silke Gillessen, Daniela E Oprea-Lager, Guillaume Ploussard, Ann M Henry, Derya Tilki, Theodorus H van der Kwast, Thomas Wiegel, James N'Dow, Malcolm D Mason, Philip Cornford, Nicolas Mottet, Thomas B L Lam

Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK., University of Aberdeen, Aberdeen, UK., Radiology Department, Netherlands Cancer Institute, Amsteram., Department of Oncological Urology, University Medical Center, Utrecht Cancer Center, Utrecht, The Netherlands., Department of Medicine, Health Science Centre, McMaster University, Hamilton, Ontario, Canada., Department of Urology, Antonius Hospital, Utrecht, The Netherlands., Department of Surgery, Central Clinical School, Monash University, Melbourne, Australia., Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Urinary and Vascular Imaging, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; Faculté de Médecine Lyon Est, Université Lyon 1, Université de Lyon, Lyon, France., Department of Urology, University Hospitals Leuven, Leuven, Belgium; Laboratory of Molecular Endocrinology, KU Leuven, Leuven, Belgium., Academic Urology Unit, University of Sheffield, Sheffield, UK., Department of Urology, Metropolitan General Hospital, Athens, Greece., Department of Urology, Wrightington, Wigan and Leigh NHS Foundation Trust, Wigan, UK., Department of Urology, University Hospitals Leuven, Leuven, Belgium., Unit of Urology, Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Patient Advocate, Hasselt, Belgium., Department of Urology, Charité University Hospital, Berlin, Germany; Department of Urology, Medical University of Vienna, Austria., Department of Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Oncology Institute of Southern Switzerland, Bellinzona, Switzerland and Università della Svizzera Italiana, Lugano, Switzerland; University of Bern, Bern, Switzerland; Division of Cancer Sciences, University of Manchester, Manchester, UK., Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, Amsterdam, The Netherlands., La Croix du Sud Hospital, Quint Fonsegrives, France; Institut Universitaire du Cancer-Toulouse, Onocopole, Toulouse, France., Leeds Cancer Centre, St. James's University Hospital and University of Leeds, Leeds, UK., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany., Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK; University of Aberdeen, Aberdeen, UK., Division of Cancer & Genetics, Cardiff University School of Medicine, Velindre Cancer Centre, Cardiff, UK., Royal Liverpool and Broadgreen Hospitals NHS Trust, Liverpool, UK., Department of Urology, University Hospital, St. Etienne, France., Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK; University of Aberdeen, Aberdeen, UK. Electronic address: .