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.
