Periprostatic Neurolysis in Prostate Cancer

Men with high-risk prostate cancer are at the greatest risk for clinical progression, with 22 to 40% developing metastatic disease within 10 years of initial treatment. Furthermore, the finding of perineural invasion (PNI) on pathology (when prostate cancer cells invade the nerves that innervate the prostate), is associated with higher Gleason grades and an approximate doubling in risk of lethal prostate cancer. As 90% of prostate cancer metastasis involve the bone marrow, and 97% of bone marrow metastasis involve the lumbar vertebrate from which the pre-ganglionic sympathetic nerves that innervate the prostate derive, targeting this neuro-anatomic connection between the prostate and its primary site of metastasis is an active area of investigation. Therefore, development of therapeutic strategies targeting nerves to prevent clinical progression after definitive therapy for prostate cancer are urgently needed. In a Phase 1a dose escalation study (NCT06703437) we recently demonstrated that periprostatic neurolysis with 5mL pure ethanol was well tolerated with no AEs. This resulted in an approximate 30% reduction in prostatic adrenergic nerve density. The goal of this study is to optimize prostatic denervation by comparing the denervation efficiency of 1 vs 2 periprostatic ethanol injections.