Established focal therapy-HIFU, IRE, or cryotherapy-where are we now?-a systematic review and meta-analysis

Abstract

Introduction: Focal Therapy (FT) is a treatment option for the treatment of limited volume clinically significant prostate cancer (csPCa). We aim to systematically review outcomes of established FT modalities to assess the contemporary baseline and identify gaps in evidence that will aid in further trial and study design.

Methods: We conducted a systematic review and meta-analysis of all primary studies reporting outcomes of FT using cryotherapy, high-intensity focused ultrasound (HIFU), and irreversible electroporation (IRE). We described patient inclusion criteria, selection tools, treatment parameters, and surveillance protocols, and pooled overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), biochemical progression (BP), biopsy, secondary treatment, sexual, and urinary function outcomes. Composite failure was defined as salvage whole gland ablation, radical treatment, hormonal therapy or transition to watchful waiting.

Synthesis: We identified 49 unique cohorts of men undergoing FT between 2008 and 2024 (21 cryotherapy, 20 HIFU, and 8 IRE). Median follow-up ranged from 6 to 63 months. Pooled OS was 98.0%, CSS 99.3%, and MFS 98.5%. Pooled BP was 9.4%/year. Biopsy was mandated post-FT within 24 months in 36/49 (73.5%) cohorts, with pooled csPCa (GG ≥ 2) rates of 22.2% overall, 8.9% infield, and 12.3% outfield. The pooled rate of secondary FT was 5.0%, radical treatment 10.5%, and composite failure 14.1%. Of 35 studies reporting sexual function, 45.7% reported a low, 48.6% moderate, and 5.7% severe impact. For 34 cohorts reporting urinary function, 97.1% reported a low impact. No differences were noted between cryotherapy, HIFU, or IRE in any of the outcomes.

Conclusion: FT with cryotherapy, HIFU, and IRE is associated with good short-intermediate term oncological and functional outcomes. However, outcome reporting is heterogeneous and often incomplete. Long-term follow-up and standardized reporting are required to better define and report FT outcomes.

Fig. 1. Focal therapy ablation patterns, study inclusion flowchart, and evolution of cohort csPCa composition over time.

A Focal therapy ablation patterns; B Study Inclusion Flowchart; C graph of proportion of clinically significant prostate cancer (csPCa) as a composition of focal therapy cohorts over time; data points represent individual cohorts; the dotted blue line is the smoothed weighted average of proportion of csPCa over time.

Fig. 2. Oncological outcomes after focal therapy.

A Pooled overall survival; B pooled cancer-specific survival; C pooled metastasis-free survival, D pooled yearly biochemical progression rate.

Fig. 3. Short- to intermediate-term oncological outcomes after focal therapy.

A Error bar plot of the rate of positive biopsy in any location, infield or outfield, subdivided into any cancer versus clinically significant (CS) cancer, stratified by modality; B pooled rate of second focal therapy (FT); C pooled rate of salvage radical therapy (both radical prostatectomy and radiation therapy); D pooled rate of composite treatment failure (salvage whole gland ablation, salvage radical therapy, salvage hormonal therapy, transition to watchful waiting).

Fig. 4. Functional outcomes after focal therapy.

A Sexual function impact: low (<10%), medium (10–30%), and high (>30%), stratified by modality; B Urinary function impact: low (<10%), medium (10–30%) and high (>30%), stratified by modality.

Fig. 5. Failure scenarios and pre-focal therapy cancer patterns.

A Potential pathways of prostate cancer progression after focal therapy (FT); B pre-FT cancer patterns or “phenotypes” that may impact on interpretation of post-FT imaging/biopsy/progression outcomes.