This research was conducted by a team of experts at Memorial Sloan Kettering Cancer Center, a world-renowned institution leading advancements in cancer treatment and innovation. Their work underscores MSK’s ongoing commitment to pioneering new models and technologies in bladder cancer research, helping to bridge the gap between laboratory findings and effective clinical applications.

Overview

This model addresses critical gaps in current bladder cancer research by providing a clinically relevant system more closely resembling human cancer than mouse or rare canine models. The research objective was to establish a robust, inducible large-animal bladder cancer model that mimics human urothelial carcinoma and supports endoscopic and catheter-based therapeutic evaluation.

Study Design

Induction strategy: Using cystoscope-guided delivery of an adenoviral Cre-recombinase vector (AdCre), the team tested two minimally invasive bladder protocols designed for compatibility with clinical endoscopic workflows.

Procedures:

Procedure I (Proc‑I): Bladder instillation of AdCre combined with N‑dodecyl‑β‑maltoside, a surfactant that disrupts the glycosaminoglycan layer to enhance urothelial transduction (1‑hour dwell; n=3).

Procedure II (Proc‑II): Superficial denudement of the urothelium at three sites followed by 1‑hour intravesical AdCre instillation (n=4).

Seven Oncopigs underwent cystoscope-based bladder tumor induction using Proc‑I (n=3) or Proc‑II (n=4).

Serial CT imaging and follow-up cystoscopy were used to monitor tumor formation and growth kinetics at 14, 21 and 28 days post-induction. Necropsy at predefined timepoints with comprehensive histopathology and staging of urothelial tumors.

Key Results

Overall, 6 of 7 Oncopigs developed endoluminal bladder tumors.  Tumor take rate was 100% with Proc‑I (3/3) and 75% with Proc‑II (3/4), demonstrating robust and reproducible induction using clinically familiar urologic procedures. Two main tumor phenotypes emerged: urothelial cell carcinomas of sarcomatoid variant and inflammatory tumors. Tumors formed within 14 days, providing a rapid readout window for preclinical intervention studies.  At day 14, Proc‑I animals exhibited pT1 tumors (superficial), while Proc‑II animals had already progressed to pT2 (muscle-invasive) disease. By day 21, Proc‑I animals displayed a mix of pT1 and pT2 tumors, whereas Proc‑II tumors remained predominantly pT2, linking procedure choice and timing directly to depth of invasion.

Conclusions

The model reproduces both non–muscle-invasive and muscle-invasive urothelial carcinoma in a large animal whose anatomy, metabolism, immunity, and procedural handling align closely with humans.  Endoscopic access, catheter-based delivery, and imaging workflows mirror standard urologic practice, making this platform particularly suited for interventional oncology, intravesical agents, and device–drug combination products. This platform enables rigorous preclinical testing of:

• Endoscopic ablative modalities (e.g., energy-based or focal therapies).
• Novel intravesical drugs, immunotherapies, and oncolytic agents requiring controlled bladder exposure.
• Device-assisted delivery and imaging-guided protocols that must be optimized before first-in-human studies.
• Flexible protocol design (Proc‑I vs Proc‑II, varied timepoints) allows sponsors to model specific clinical scenarios, from early superficial lesions to more advanced muscle-invasive disease.