Urothelial resurfacing with irreversible electroporation for adjuvant therapy of bladder cancer

The National Cancer Institute awarded the University of Massachusetts a Project Grant totaling $706,479 on June 11, 2026, under the Cancer Detection and Diagnosis Research program (CFDA 93.394) to develop and validate whole bladder urothelial resurfacing using irreversible electroporation as adjuvant therapy for non-muscle invasive bladder cancer.

The project addresses the challenge of local tumor recurrence in bladder cancer patients following standard transurethral resection of bladder tumor and intravesical adjuvant therapy. Microscopic tumors and premalignant lesions within the urothelial layer escape these treatments and drive recurrence in most early-stage patients within five years. The funded research will develop technology to extend ablative techniques across the entire bladder using irreversible electroporation—a mechanism that induces rapid cell death through microsecond-length pulsed electric fields without affecting the surrounding tissue matrix. Prior work by the research team demonstrated feasibility of this approach in the ureter, bile duct, and bronchus in animal models, and preliminary findings established the technical foundation for bladder application. The project will investigate synergy between whole bladder urothelial resurfacing and intravesical adjuvant therapy to improve outcomes.

Performance will occur in Massachusetts from the award date through May 31, 2031.

Abstract

Over 70% of bladder cancer (BCA) patients are diagnosed with early-stage and localized non-muscle invasive disease (NMIBC), yet achieving durable cancer-free survival remains a significant challenge. Most of these patients will experience local tumor recurrence within five years following standard of care (SOC) transurethral resection of bladder tumor (TURBT) and intravesical adjuvant chemo- or immunotherapy. Recurrence is driven by microscopic tumors and premalignant lesions dispersed within the urothelial layer that survive and escape these treatments. As TURBT effectively treats tumors visible on imaging, current research has predominantly focused on drugs and biologics for improving intravesical adjuvant therapy. In this proposal we pose the provocative question whether a TURBT-like ablative technique can be extended to debulk malignancy in the entire bladder and investigate the synergy with intravesical adjuvant therapy in improving outcomes. Our objective is to address this technology and knowledge GAP by developing and validating whole bladder urothelial resurfacing (WBUR) using irreversible electroporation (IRE). During IRE, microsecond-long pulsed electric fields (PEF) are used to induce rapid cell death by catastrophic permeabilization of the cell membrane, without affecting the extracellular matrix (ECM) within the treated tissue. In prior work, we designed devices that utilized this unique mechanism of IRE for performing penetrative ablation in the ureter, bile duct and bronchus of swine while preserving lumen function. Our findings provided strong rationale for IRE being an ideal candidate for WBUR as alternate techniques such as thermal ablation or ionizing radiation must be performed with extreme care in the bladder to avoid perforation or fistula formation. In subsequent preliminary work we developed technology to demonstrate the feasibility and safety of WBUR with IRE in a RAT model of BCA and scalability in human-sized swine bladder. In aim 1, we will investigate the cancer treatment efficacy of combination WBUR and intravesical adjuvant therapy. In aim 2, validate WBUR derived liquid biopsy for monitoring cancer status. In aim 3, engineer PEF delivery strategy to enhance the safety and specificity of WBUR. The innovation of our proposed work is defined by developing whole bladder ablation as a debulking strategy and examining its synergy with SOC adjuvant therapy (aim 1), enabled by new electrode paradigm and PEF delivery strategy (aim 3), monitoring by an unconventional liquid biopsy approach (aim 2). Our work can immediately aid the management of NMIBC patients who cannot undergo radical cystectomy, with future application as a cancer prevention strategy in high-risk patients. Success of individual aims will result in major contributions to the topics of IRE, BCA treatment and diagnosis.