Combination of Radiation Therapy and Irreversible Electroporation for Intermediate-Risk Prostate Cancer (RTIRE): A Phase 1 Trial.

Abstract

Background Irreversible electroporation (IRE) is a nonthermal local therapy for prostate cancer (PCa). However, the feasibility, outcomes, and safety of reduced-dose radiation therapy (RT) following IRE (RTIRE) for the treatment of intermediate-risk PCa are unknown. Purpose To assess the feasibility of RTIRE for the treatment of intermediate-risk PCa. Materials and Methods This was a prospective study from May 2022 to April 2024 and included participants with intermediate-risk PCa with a focal index lesion (grade group 2 or 3 disease) visible at MRI. Participants underwent RTIRE (to 32.5 Gy in five fractions) with follow-up at 3, 6, 9, and 12 months. The primary end point was enrollment feasibility. Secondary end points included early oncologic control, quality-of-life outcomes, and adverse events. The Wilcoxon rank-sum test was used to compare continuous values at different time points. Results A total of 10 men (median age, 66 years [IQR, 61-72 years]) successfully completed RTIRE. At 12 months, no residual disease was detected at biopsy in 100% (10 of 10) of participants. Median prostate-specific antigen level decreased from baseline (7.65 ng/mL) to 3 months (0.98 ng/mL; <i>P</i> = .002) and remained stable at 12 months (0.56 ng/mL; <i>P</i> = .002 vs baseline). Median Expanded Prostate Cancer Index Composite for Clinical Practice score increased from baseline (3.5 [IQR, 3-8]) to 6 months (13 [IQR, 9-19]; <i>P</i> = .02), returning to near baseline at 12 months (6 [IQR, 5-15.75]; <i>P</i> = .05). International Index of Erectile Function score decreased from baseline (median, 23.5) to 6 months (median, 12; <i>P</i> = .02), with recovery by 12 months (median, 22; <i>P</i> = .16 vs baseline). Median International Prostate Symptom Score was stable at 12 months (<i>P</i> = .56 vs baseline). No severe adverse events occurred (100% [27 of 27] of adverse events were grade 1 or 2). Conclusion Treatment of participants with intermediate-risk PCa with RTIRE was feasible and showed no clinically meaningful decline in patient-reported outcomes and no severe adverse events. Clinical trial registration no. NCT05345444 © RSNA, 2026 <i>Supplemental material is available for this article.</i> See also the editorial by Nezami and Unger in this issue.