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CUAJ %u2022 FEBRUARY 2025 %u2022 VOLUME 19, ISSUE 2 67Focal therapy to treat prostate cancerexhibited lower mean percent PSA level reductions, higher rates of in-field negative post-treatment biopsy, and superior potency maintenance compared to HIFU patients.33 Five-year followup outcomes from the pivotal TULSA trial were also recently reported, showing durable disease control and a favorable safety profile.36Considering that a substantial number of men undergoing FT may eventually necessitate salvage therapy, it was intriguing to examine initial outcomes following salvage radical prostatectomy after IRE. Among 39 patients, there were no reported SAEs following surgery.37 With a median followup of 17.7 (interquartile range 11.8%u201326.4) months, urinary continence and erectile function were maintained in 34 patients (94.4%) and 18 patients (52.9%), respectively, while overall quality of life remained consistent. Positive surgical margins (PSMs) were identified in 10 patients (25.6%), with six (15.4%) displaying significant PSMs. Three patients necessitated further therapeutic interventions following salvage radical prostatectomy.37Functional outcomesRates of SAEs were generally low, ranging from 0%u201314% across 19 HIFU studies, with a median of 2%.5 SAEs included a myocardial infarction (IRE), rectourethral fistula (FLA), UTI, and gross hematuria. In a recent large, retrospective review, strictures developed in 133/1290 patients (10.3%) and urinary fistulas developed in 16/1240 (1.3%) of patients following HIFU.38Most studies used patient-reported outcomes to monitor pad-free rates post-treatment. All modalities reported >95% median pad-free rates post-treatment, with many showing no change from baseline.5Data on erectile function is more variable. Most studies show no significant decline in patient-reported measures of erectile function (such as International Index of Erectile Function or Sexual Health Inventory for Men) after treatment. Multiple focal brachytherapy studies did show a decline in erectile function after treatment, with new-onset ED rates as high as 50%. ED rates after HIFU were estimated at 20%, with up to a 17% increased use of PDE5 inhibitors. Six studies of IRE showed a decline in erectile function after treatment, although a propensity score-matched analysis of IRE vs. robotic prostatectomy did show a statistically significant difference favoring IRE.5A comparative trial of IRE vs. HIFU showed the proportion of patients experiencing a severe AE (%u2265grade III) ranged from 0%u20138%, and that both modalities were associated with positive functional outcomes, as well as maintenance of quality of life after treatment.33Ghoreifi et al recently demonstrated that after a median followup of 43 months, 19.6% of patients treated with FT regretted their decision. Higher PSA at nadir, presence of cancer on followup biopsy, bothersome postoperative urinary symptoms, and ED were independent predictors of treatment decision regret.39Canadian involvementIt is noteworthy that Canada has been at the forefront of advancing evidence-based FT. Two prostate cryoablation programs initiated in Canada in the 1990s have yielded over 50 peer-reviewed publications.40Canadian researchers published foundational preclinical and phase 1 clinical trials over a decade ago for focal laser ablation and MRI-guided transurethral ultrasound therapy of the prostate gland.41-43 Canadian sites also contributed patients to early studies of TOOKAD%u00ae Soluble photodynamic therapy.44 More recently, Canada led phase 1 and 2 trials of MRI-guided focused ultrasound ablation for PCa.44-48 A Canadian group has also revealed the importance of systematic control biopsies when assessing the response to FT, regardless of PSA kinetics or MRI results.35Where are we goingCurrently, there are five clinical trials in Canada focused on energy-based ablation of PCa actively seeking participants for enrollment (Table 3). The CAPTAIN trial is a RCT comparing radical prostatectomy to TULSA (subtotal) for treating localized, intermediate-risk PCa.49The HDR Focal Study is exploring the feasibility of using focal HDR brachytherapy for well-defined multiparametric MRI visible disease.50 There is a single-arm, prospective study of in bore MRI-guided focal laser ablation (MRgFLA) in patients with early-stage PCa.51 There is a phase 2, multicenter, RCT assessing whether prostatespecific membrane antigen-positron emission tomography (PSMA-PET) can improve diagnostic accuracy for the primary staging of PCa for patients undergoing FT, thereby reducing residual and recurrence disease.52Lastly, the WIRED trial is a pan-Canadian, investigatorinitiated, non-randomized clinical trial examining the oncologic benefit and safety of IRE for intermediaterisk PCa.53In the U.S., there are several ongoing trails. The PRESERVE trial, a pivotal study investigating irreversible electroporation for ablating prostate tissue in intermediate-risk PCa patients, has successfully reached its enrollment target.54 Preliminary results show a 67.6% (52.3%u201382.2%) reduction in PSA at six months, 8.3% rate of grade 3 AEs, and no grade %u22654 AEs. Final results