Introduction: There is a pressing need for the development of new devices facilitating advanced minimally invasive approaches for the in situ treatment of bladder cancer (BC). To this end, a new cystoscopic compatible cryocatheter (UroAblate) has been developed. When paired with the novel Pressurized Subcooled Nitrogen (PSN) cryoconsole, the cryocatheter delivers ultracold ablative temperatures to a targeted tissue in a closed loop manner. In this study, we evaluated cryocatheter performance for its potential use for cystoscopic in situ ablation BC. Methods: A ~1m cryocatheter with a distal 1.5cm ablation tip (connected to PSN) was passed through the working channel of a Ambu cystoscope. A laparoscopic approach was also utilized to visualize the transmural extension of the ice propagation. Evaluations included a 37°C ultrasound gel model, tissue engineered BC model and a chronic porcine study (4 animals, 7 day survival) wherein 10 lesions/animal were created throughout the bladder (bladder wall, trigone region, UO and distal ureter). Performance assessment included ice ball size, isotherm profile and destruction area. Single and double 0.5, 1, 1.5 and 2 min freeze protocols were evaluated. Results: Bench studies demonstrated the generation of a 1.6cm iceball and the penetration of the -20°C isotherm to 0.87cm following 2 mins. Analysis of tissue destruction using a BC tumor model revealed the creation of a 350mm3 and 448mm3 ablated volume following a single or double 2 min freeze, respectively. Porcine studies demonstrated the consistent generation of transmural lesions following freezing (single or double) for =1.5min regardless of tissue thickness (range: 0.4cm to 1.2cm). All animals were found to have good overall health (maintained weight, appetite, mobility, energy levels, etc.) through the recovery period. No significant deviations were noted in CBC and serum chemistry bloodwork with the exception of elevated Creatine Kinase levels. Importantly, no fistulas or bowel/bladder perforations were noted in any animals. Conclusions: This study demonstrated that the cryocatheter was able to rapidly and effectively freeze targeted tissue via a cystoscopic approach. The results showed the device was able to consistently ablate a >1cm area using a single 2 minute freeze protocol across all models. Analysis of the ablation efficacy revealed ~80% destruction within the overall frozen mass. Although further testing and refinement are needed, these studies demonstrated the potential of this new approach to provide a next-generation strategy for the treatment of BC. SOURCE OF Funding: National Institutes of Health National Cancer Institute Grant No. 1R43CA210761-01A1 awarded to CPSI Biotech.
