Preliminary Results of First-in-Human Intravesical Cryotherapy of Nonmuscle-invasive Bladder Cancer

Introduction: Cryotherapy with CO2 is commonly used to treat superficial papillary lesions of the skin for many years. Following preliminary results in an animal model, we present our first-in-human phase 1 clinical safety trial and preliminary results in treating low-grade noninvasive papillary lesions of the bladder with cryoablation. Materials and Methods: Patients with up to 3 papillary lesions and a maximum of 10 mm in size were recruited in a single institution. Patients with previous high-grade disease and/or positive cytology were excluded. Treatment included bladder CO2 insufflation and applying liquid CO2 cryospray to each lesion in 2 cycles of 15 seconds each, with 15 seconds of thawing between cycles. Cystoscopy and treatment site biopsy were performed 4-6 weeks after treatment. Routine surveillance with office cystoscopy was performed every 3 months for 1 year thereafter. Results: 11 men and 2 women ages 59 to 79 years old were included. Overall, 24 lesions were treated. No complications were noted during treatment or follow-up. Pathological biopsy of the treatment sites 6 weeks after treatment detected residual low-grade TCC in three patients and high-grade TCC in one patient, which was attributed to suboptimal lesion freezing due to the initial learning curve in the first few patients, and misdiagnosis of high-grade disease in an additional patient. Two lesions were resected due to the inability to properly treat them with a rigid device. Overall, 20/24 of the lesions were negative for cancer on confirmatory biopsy (83%). Conclusions: Cryotherapy utilizing CO2 spraying for small low-grade NMIBC lesions is safe and feasible. Pathological analysis confirms efficacy in tumor eradication when properly selected and adequately treated by cryospray. This novel treatment may be used as an office procedure and might offer a potential paradigm shift in the treatment of low-grade non-muscle invasive bladder cancer.