Neoadjuvant Intraprostatic OnabotulinumtoxinA Before Radical Prostatectomy for High-Risk Localized Prostate Cancer

High-risk localized prostate cancer is associated with a substantial risk of adverse pathological features and disease recurrence despite definitive treatment with radical prostatectomy. Emerging evidence suggests that neural signaling within the prostate tumor microenvironment contributes to tumor growth, progression, and treatment resistance. OnabotulinumtoxinA (BOTOX®), a neurotoxin that blocks acetylcholine release, has demonstrated biological effects in prostate tissue and may provide a novel approach to modulating tumor-associated neural pathways.

This single-center, prospective, randomized, single-blind, placebo-controlled pilot study will enroll 30 men with high-risk or very-high-risk localized prostate adenocarcinoma who are scheduled to undergo radical prostatectomy. Participants will be randomized in a 1:1 ratio to receive either a single transrectal ultrasound-guided intraprostatic injection of onabotulinumtoxinA (50 units) or an equivalent-volume normal saline placebo 6 to 8 weeks prior to surgery. Participants will remain blinded to treatment assignment.

The primary objective is to evaluate study feasibility and safety, including participant accrual, protocol adherence, successful completion of intraprostatic injection and planned surgery, and the incidence and severity of adverse events. Secondary objectives include evaluation of pathological outcomes at prostatectomy, including Gleason score, perineural invasion, stromogenic component, tumor burden, pathological stage, and surgical margin status. Early postoperative PSA outcomes will also be assessed. Exploratory analyses will evaluate time to biochemical recurrence following radical prostatectomy.

This pilot study is not powered to demonstrate clinical efficacy. Instead, it is designed to establish the safety and feasibility of neoadjuvant intraprostatic onabotulinumtoxinA and generate preliminary biological and pathological data to support future studies investigating neural modulation as a therapeutic strategy in prostate cancer.

Inclusion criteria

• Male, ≥ 45 years
• Histologically confirmed prostate adenocarcinoma
• Gleason score ≥8 on biopsy
• Candidate for and scheduled to undergo RALP for primary treatment
• ECOG 0-2
• Able to read, speak, and understand English
• Able to provide informed consent

Exclusion criteria

• Prior prostate cancer therapy (radiation, ADT, chemotherapy)
• Metastatic disease
• Known hypersensitivity to botulinum toxin
• Neuromuscular disorders (e.g., myasthenia gravis)
• Active infection, coagulopathy, or contraindication to transperineal injection
• Medications significantly affecting neuromuscular transmission (clinically relevant)
• Any condition compromising safety or protocol compliance