BACKGROUND AND OBJECTIVE:Long-term outcome data for focal therapy using high-intensity focused ultrasound (HIFU) or cryotherapy for nonmetastatic prostate cancer are needed. We report 10-yr cancer control outcomes. METHODS:Patients with nonmetastatic prostate cancer who underwent primary focal HIFU or cryotherapy and had at least 6 mo follow-up were identified from the UK HIFU Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) prospectively maintained registries. The intervention included up to two focal ablative sessions. The primary outcome was cancer-specific mortality. Secondary outcomes were all-cause mortality, metastasis, local retreatment, radical treatment, and androgen-deprivation therapy (ADT) use. KEY FINDINGS AND LIMITATIONS:A total of 3477 patients (HIFU: n = 2897; cryotherapy: n = 580) were included from 14 UK centres (2004-2024). A total of 48%, 23%, and 25% had European Association of Urology (EAU) 2025-version favourable intermediate-, unfavourable-intermediate-, and high-risk disease, respectively. Ten-yr cancer-specific mortality was 0.13% (95% confidence interval [CI] = 0.027-0.45%). Ten-yr all-cause mortality and metastases were 12% (95% CI = 8.8-15%) and 3.3% (95% CI = 2.1-4.9%), respectively. Ten-yr ADT use was 14% (95% CI = 11-17%). Ten-yr local retreatment and radical treatment were 33% (95% CI = 30-37%) and 30% (95% CI = 27-34%), respectively, on an intention-to-treat basis. In a post hoc per-protocol analysis, undertaken to estimate outcomes under stricter adherence to the two focal ablative session protocol, patients who underwent radical treatment despite being potentially eligible for a further focal ablative session were censored at the time of radical treatment; 10-yr local retreatment and radical treatment were 13% (95% CI = 11-16%) and 8.9% (95% CI = 6.9-11%), respectively. The observational study design is the main limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS:Focal therapy using up to two sessions of focal HIFU or cryotherapy could be considered as a first-line treatment for well-selected patients of nonmetastatic prostate cancer alongside radical treatment. Future research priorities should include the development of a dedicated prognostic risk calculator, further prospective assessment of focal therapy for high-risk disease, and improvements in the detection and management of locally recurrent disease.

BACKGROUND AND OBJECTIVE:Irreversible electroporation (IRE) is an emerging non-thermal focal therapy for localized prostate cancer (PCa), offering tissue-selective ablation with functional preservation. This review aimed to delineate the 'ideal' candidate for primary IRE and provide practical guidance. METHODS:A narrative review (2014-2025) of primary IRE for localized PCa was conducted, including prospective series, multicentre registries, comparative studies, and systematic reviews. We synthesized baseline characteristics, lesion features, ablation strategy, oncologic/functional outcomes, and complications, focusing on cancer control and safety. RESULTS:The best outcomes were reported in men with magnetic resonance imaging-visible, organ-confined intermediate-risk (International Society for Urological Pathology [ISUP] 2-3) PCa, typically presenting a single dominant unilateral index lesion characterized by multiparametric MRI and biopsy. Contemporary series show in-field ablation of clinically significant cancer in ~80-90% with high functional preservation. The main limitation is out-of-field recurrence (~15-25% of failures), reflecting PCa multifocality. In-field persistence at 12 months was ~16% in the PRESERVE trial. Lesion size is a key practical constraint; current evidence and electrode geometry favour targets generally ≤20 mm. Limited comparative evidence, largely from a single study, suggests better oncologic control with hemi-gland IRE (clinically significant PCa persistence 8.6%) versus focal ablation (25%), whereas focal IRE better preserves erectile function. CONCLUSIONS AND CLINICAL IMPLICATIONS:Primary IRE appears safe and effective in selected localized PCa. The ideal candidate has unilateral MRI-visible, organ-confined ISUP 2-3 disease, prostate-specific antigen density <0.15-0.20 ng/mL/cm3, and a lesion small enough for reliable electrode coverage. Hemi-gland templates may improve oncologic reliability, whereas focal ablation maximizes functional outcomes. PATIENT SUMMARY:IRE is a focal, non-thermal treatment for localized PCa that can control the treated lesion while usually preserving urinary continence and often erectile function. Cancer can still occur elsewhere in the prostate after treatment, so follow-up is essential.

Importance:Patients with recurrent prostate cancer after previous radiotherapy typically have poor survival. Those with recurrences prostate confined might be suitable for salvage focal therapy (sFT) or salvage radical prostatectomy (sRP). sFT may offer good cancer control with comparatively less toxic effects, but outcomes beyond 5 years have not been reported, and no study has compared sFT to sRP. Objective:To compare cancer control and perioperative complications among patients after sFT vs sRP. Design, Setting, and Participants:In this international, multicenter cohort study of matched comparison data, patients undergoing sFT were derived from the prospective UK HIFU (high-intensity focused ultrasound) Evaluation and Treatment and International Cryotherapy Evaluation registries (9 centers; 2006-2024) and the prospective UK Focal Recurrent Assessment and Salvage Treatment cohort study (6 centers; 2014-2018). Patients undergoing sRP were derived from an international retrospective registry (12 centers in 8 countries; 2000-2021). Patients with biopsy-confirmed, localized recurrent prostate cancer postradiotherapy, either external beam radiotherapy, brachytherapy, or both, were included. Data were analyzed from March to July 2025. Exposures:sFT using HIFU or cryotherapy vs sRP. Main Outcomes and Measures:The primary outcome was cancer-specific survival up to 10 years. Secondary outcomes were overall survival, any perioperative complications (Clavien-Dindo grades 1-5), and major perioperative complications (Clavien-Dindo grades 3-5). Comparisons were made on matched patients following 1:1 cardinality matching within individual multiply-imputed datasets. Matching variables used were radiotherapeutic treatment, years between primary and salvage treatments, European Association of Urology recurrence risk group, and presalvage age, prostate-specific antigen, prostate volume, grade group, T stage, and androgen-deprivation therapy use. Results:A total of 923 patients were eligible for matching (419 undergoing sFT and 504 undergoing sRP). Of the patients undergoing sFT, 325 (77.6%) underwent HIFU and the remainder cryotherapy, with 241 (57.5%) treated with quadrant ablation. Of patients treated with sRP, 376 (74.6%) underwent open surgery and the remainder robot-assisted surgery. For sFT vs sRP, 10-year cancer-specific survival was 92% (95% CI, 86%-98%) vs 99% (95% CI, 97%-100%), with no statistically significant difference (restricted mean time lost, -0.09 years; 95% CI, -0.22 to 0.03 years; P = .15; subdistribution hazard ratio, 0.45; 95% CI, 0.05-4.00; P = .47). There was no statistically significant difference in 10-year overall survival (restricted mean survival time, -0.13 years; 95% CI, -0.86 to 0.60 years; P = .72). Undergoing sRP was associated with statistically significant higher odds of any complication (adjusted odds ratio, 24.20; 95% CI, 12.94-45.27; P < .001) and major complication (adjusted odds ratio, 9.31; 95% CI, 3.42-25.36; P < .001). Conclusions and Relevance:In this cohort study, sFT and sRP were effective for treating localized radiorecurrent prostate cancer, while sFT was associated with fewer perioperative complications. sFT may provide a favorable therapeutic ratio for many patients with localized radiorecurrent prostate cancer.

BACKGROUND AND OBJECTIVE:Magnetic resonance imaging (MRI)-led active surveillance (AS) for prostate cancer uses prostate-specific antigen (PSA) and MRI for regular monitoring with biopsy only when indicated by changes in MRI or PSA density. METHODS:This clinical cohort, which started AS between February 2000 and July 2023, includes those with (1) Gleason score (GS) ≤3 + 4, (2) PSA <20 ng/ml, and (3) at least two MRI scans. The primary outcome was event-free survival (EFS) defined as histological upgrade to GS ≥4 + 3 or transition to treatment. Patients were risk stratified by baseline MRI visibility and Gleason pattern 4, and Kaplan-Meier curves were used to compare groups. KEY FINDINGS AND LIMITATIONS:The cohort consisted of 1150 patients with a median follow-up of 64 mo per person overall (quartiles: 32, 107). At baseline, of these 1150 patients, 412 (36%) had GS 3 + 4, 627 (55%) had an MRI-visible lesion, and 201 (17%) had MRI-visible Gleason 3 + 4 disease. The EFS rate at 5 yr was 91% (95% confidence interval: 88-94%) for nonvisible GS 3 + 3, 71% (65-78%) for MRI-visible GS 3 + 3, 70% (63-78%) for nonvisible GS 3 + 4, and 44% (35-54%) for MRI-visible GS 3 + 4. A total of 487 patients had follow-up biopsies, with 74 having more than one, and histological upgrade to GS ≥4 + 3 was uncommon, occurring in 67 patients. Progression to nodal or bone metastases occurred in ten patients and only in those who had declined the recommended follow-up MRI and/or biopsies. Thirty patients chose treatment despite having stable characteristics, and 31 were lost to follow-up. CONCLUSIONS AND CLINICAL IMPLICATIONS:MRI visibility and secondary Gleason pattern 4 at baseline are associated with progression to treatment and to primary Gleason pattern 4 during MRI-led AS.

The inclusion of imaging as a triage test in diagnostic guidelines for prostate cancer (PC) has introduced a visible target for guiding treatment allocation and disease management. Focal therapy (FT) is a promising approach with a low side-effect profile for treating magnetic resonance imaging (MRI)-visible PC within a limited framework of guideline recommendations or clinical trials. On the basis of accumulated clinical and research experience, we present a systematic approach to FT indications for ablation of visible targets that includes imaging findings, margin delineation, and energy selection. Confirmation of eligibility for FT is associated with the choice of energy source. We propose a 10-step framework that incorporates the contribution of all MRI sequences, the cancer growth pattern within the zonal anatomy to establish a margin around the MRI-visible lesion, safeguards for critical anatomic structures, and guidance for energy selection on the basis of specific properties. We discuss the key principles underlying this process. The aim of this methodology is to standardise FT interventions for MRI-visible PC and contribute to the development of a reproducible, stable treatment protocol. Quality control of the ablation procedure is crucial for broadening access to this technique beyond the confines of current regulatory pathways. Patient summary:We propose a method for using results from magnetic resonance imaging (MRI) scans to guide targeted treatment of visible prostate cancer lesions. This will help to ensure accurate coverage and eradication of all of the cancer while minimising side effects.

PURPOSE OF REVIEW:The management of localized prostate cancer (PCa) is shifting towards tissue-preserving strategies such as active surveillance and focal therapies. Intermediate-risk PCa, especially ISUP Grade Group 2 (GG2), encompasses a heterogeneous disease spectrum, complicating patient selection for conservative treatments. Cribriform architecture, a Gleason pattern 4 subtype, is associated with poorer outcomes and currently contraindicates active surveillance However, these conclusions are mainly based on retrospective data from older cohorts, raising questions about cribriform's independent prognostic value versus Gleason pattern 4 burden. RECENT FINDINGS:Cribriform pattern correlates strongly with increased Gleason pattern 4, which is linked to adverse features such as biochemical recurrence and tumour upstaging. The independent impact of cribriform remains unclear due to limited regression analyses and variable reporting. Cribriform detection on biopsy and MRI is challenging, often leading to underestimation and complicating risk stratification. SUMMARY:Despite current guidelines excluding cribriform-positive patients from active surveillance, emerging evidence suggests some patients with limited cribriform and low Gleason 4 percentage could be candidates for active surveillance or focal therapies. Prospective studies with standardized cribriform quantification and imaging evaluation are needed to clarify these issues.

Introduction RECONCILE (ClinicalTrials.gov:NCT04340245) will identify molecular and radiomic markers associated with clinical progression and radiological progression events in a cohort of localised, newly diagnosed Gleason 3 + 4 tumours. Molecular markers will be correlated against standard of care MRI-targeted histology and oncological outcomes. Methods RECONCILE is an ethics approved (20/LO/0366) single centre, prospective, longitudinal, observational cohort study of recently diagnosed (within 12 months), organ-confined Gleason 3 + 4 cancers (MCCL ≤10mm) currently under active surveillance. 60 treatment-naïve participants with a concordant MRI lesion (Likert score 4 or 5) and PSA ≤ 15 ng/ml will be recruited. Blood, urine and targeted prostate tissue cores will be subject to next generation sequencing at baseline and one year in all participants. Semen will be collected from a specified sub-population. Baseline and interval MR images will be extracted from standard of care prostate MRI ahead of radiomic analysis. Data extracted from radiological and biological samples will be used to derive the association of molecular change and radiological progression, the primary outcome of the study. To compensate for spatial intratumoral heterogeneity and inherent sampling bias, a molecular index will be derived for each participant using the molecular profile of tumour tissue at both baseline (MolBL) and one year (MolFU). We will extract a ΔMolBL:MolFU score for each participant. Molecular progression will be defined as a MolBL:MolFU score >95% CI of the combined ΔMolBL scores. Radiological progression is defined as a PRECISE score of 4 or 5. The study is powered to detect an association with a statistical power of 80%. Results Recruitment began in July 2020 (n = 62). To date, 37 participants have donated tissue for analysis. Conclusion We have designed and implemented a prospective, longitudinal study to evaluate the underlying molecular landscape of intermediate risk, MR-visible prostate tumours. Recruitment is ongoing.