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

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 Rouviere, Lisa Moris, Marcus G. Cumberbatch, Michael Lardas, Matthew Liew, Thomas Van den Broeck, Giorgio Gandaglia, Nicola Fossati, Erik Briers, Maria De SantisStefano 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*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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

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

Evidence acquisition: 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.

Evidence synthesis: 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.

Conclusions: 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.

Patient summary: 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. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)405-423
Number of pages19
JournalEuropean Urology Oncology
Volume4
Issue number3
Early online date8 Jan 2021
DOIs
Publication statusPublished - 1 Jun 2021

Keywords

  • Systematic review
  • Evidence synthesis
  • Focal ablative therapy
  • Radical treatment
  • Localised prostate cancer
  • Oncological and functional outcomes
  • Limitations of evidence base
  • Clinical practice guidelines and recommendations
  • ACTIVE SURVEILLANCE

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