Phase 2 NanoKnife IRE non-thermal ablation boost vs focal radiation boost in SBRT

Memorial Sloan Kettering Cancer Center is running this randomized Phase 2 IRRADIANT study (NCT07548164) to test whether an irreversible electroporation (IRE) “boost” to the dominant intraprostatic lesion can match a standard radiation boost when both groups also receive whole-prostate stereotactic body radiotherapy (SBRT). The investigational device is the NanoKnife system (AngioDynamics), which delivers high-voltage electrical pulses that create permanent nanopores in tumor-cell membranes, causing cell death through non-thermal ablation (i.e., not primarily heat-based). In the control arm, the “boost” is delivered as an intensified, focal external beam radiation therapy (EBRT) dose to the lesion, leveraging dose painting rather than ablation. The primary question is non-inferiority on local control assessed by negative biopsy rate at 2 years, in patients with intermediate-risk prostate cancer (clinical stages T1–T3b) who are candidates for definitive SBRT. Today’s care for intermediate-risk localized prostate cancer commonly includes definitive radiation (often SBRT or conventionally fractionated EBRT) with selective short-course androgen-deprivation therapy for unfavorable features, and some centers intensify with a focal radiation boost or brachytherapy boost; this trial asks whether a focal, non-thermal ablation boost can achieve comparable tumor sterilization while potentially shifting the urinary/sexual toxicity tradeoffs.