Current ablative modalities include high-intensity focused ultrasound (HIFU), cryoablation, focal laser, irreversible electroporation (IRE), and photodynamic therapy (PDT) which are FDA- approved for the treatment of prostate tissue only.140 Patient selection criteria in reported studies have varied widely as has treatment planning approach (e.g., lesion-based focal therapy, hemi-ablation, whole-gland). An early randomized trial demonstrated that focal PDT lowered the likelihood of cancer progression and rates of surgery compared to active surveillance.141 However, active surveillance remains the preferred approach for patients with low-risk prostate cancer.  Several institutional, multi-site, and population-based studies have reported outcomes of various ablative therapies for intermediate-risk disease; however, in the absence of randomization, non-standardized protocols, and insufficient follow-up, the role of ablative therapy in the management of clinically localized prostate cancer remains to be defined.142 Several studies report in-field recurrence rates of 10-40% for any disease, and generally <20% for residual pattern 4 across treatment modalities. However, no trials have compared ablative approaches to each other and detailed outcomes including frequency of salvage radical treatment, and long-term oncologic outcomes are lacking. Prospective trials publishing early results in focal therapy for prostate cancer demonstrate feasibility and safety. The HIFI study was a nonrandomized prospective study of over 3,300 patients with predominantly intermediate-risk prostate cancer comparing radical prostatectomy to HIFU. The study demonstrated that 30-month salvage treatment-free survival with whole gland or subtotal HIFU was noninferior to that of radical prostatectomy with fewer urinary and sexual side effects. Evidence remains very limited by 2-3 years of follow up, lack of randomization, and large age difference (median 74.7 versus 65.1 years in HIFU versus radical prostatectomy groups, respectively).143 In another single-arm phase 2b multicenter study, MRI-guided focused ultrasound focal therapy for intermediate-risk prostate cancer achieved a 24-month in-field disease-free rate of ~88% (defined as Grade Group ≥2 cancer in the treated area) with potential to safely delay or eliminate the need for radical whole-gland treatment in the long term. There are no RCTs comparing HIFU to standard of care treatment modalities including radical prostatectomy, radiation, or active surveillance. While HIFU may have benefit in select patients, its long-term efficacy relative to standard treatments remains unproven, and the appropriate patient population remains undefined. The panel cautions against wide implementation of HIFU in the absence of high-level evidence. Retrospective Surveillance, Epidemiology, and End Results (SEER) studies have examined population-based outcomes from cryoablation compared to radiation in low- and intermediate-risk patients, and differences in patient selection temper any conclusions.144, 145 There are no rigorous, contemporary trials comparing cryoablation to surgery or radiation therapy. The Panel considers cryotherapy to be a non-standard option for intermediate-risk patients. Similarly, published data on focal laser ablation is limited to single center retrospective series comparing selected patients to younger and healthier patients undergoing prostatectomy or radiation therapy. No clear difference in cancer-specific survival is demonstrated.  Other modalities including IRE and PDT are being tested in intermediate-risk prostate cancer. Early functional outcomes show minimal urinary and sexual side effects, but oncologic outcomes comparing their use to standard of care are not proven. Currently, the Panel believes that broader use of ablative techniques should be limited to clinical trial enrollment. They can be used in appropriately informed patients with intermediate-risk prostate cancer declining standard therapies, and ideally in a prospective study.146 Patients with low-risk cancers should still be offered active surveillance. Patients considering ablation should be counseled regarding side effects and recurrence risk and should be followed post-ablation with routine PSA, MRI, and biopsy tailored to their specific health and cancer characteristics to detect disease, persistence, or recurrence.147