An open-label phase 1, window-of-opportunity study of ultrasound-guided long acting periprostatic neuraxial block with ethanol in patients with high-risk prostate cancer.

391 Background: Patients (pts) with high-risk prostate cancer (PCa) have an elevated risk of disease recurrence/progression after definitive therapy. These pts also exhibit increased levels of adrenergic nerve density on PCa histology. Pre-clinical evidence from murine models of PCa suggest that PCaNeurolysis of periprostatic adrenergic nerves inhibits cancer progression and metastasis by inhibiting angiogenesis, altering cancer metabolism, and inhibiting cell migration (PMC5783182). Pure Ethanol (>99%) injection for neurolysis is FDA-approved in chronic cancer pain and may have a survival benefit in late-stage cancers (PMC1242819). Ultrasound-guided (US) short-acting periprostatic neuraxial block with lidocaine is commonplace in urologic practice. Thus, PCaNeurolysis with ethanol may have both a protective effect in high risk PCa and be feasibly implemented. Methods: Pts with NCCN high risk PCa who were interested and eligible for surgery, and who did not have any prior PCa treatments received in-office US guided PCaNeurolysis with either 3mL or 5mL of pure ethanol 4 to 6 weeks prior to radical prostatectomy (surgery was not delayed for trial participation). Dose escalation was determined by keyboard design with 6 pts per group (dose limiting toxicity [DLT] period = 6 weeks; DLT ³ Grade 3 events). Results: Dose escalation: 12 pts, median age 68, were treated at 2 dose levels: 3/5mL (n=6/6) with no DLTs in either group, suggesting 5mL was maximal tolerated dose to use in future studies. Additionally, no off-target effects including no decrease in erectile function (Sexual Health Inventory for Men score), no increase in urinary symptoms (International Prostate Symptom Score), and no added difficulty (eg. Destruction of tissue planes) during prostatectomy were observed in any pts. 7 pts underwent prostatectomy (43% cT3a) and were included in secondary analysis: median decrease in adrenergic density on final pathology (35%), ≥pT3a (0%), 18month biochemical recurrence (14%). Conclusions: PCaNeurolysis with ethanol was well tolerated, and 5mL was the maximum tolerated dose to use in future studies. Histologically significant decrease in adrenergic nerve density was observed suggesting the intervention acts upon its intended target, and the intervention may have antitumor activity (43% pre-injection cT3a, but 0% ≥pT3a on final pathology after injection). These Phase 1 results encourage continued investigation of PCaNeurolysis in high risk PCa pts.