CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer

Bladder cancer is the most common urinary tract cancer and the 5th most common cancer in the US (1). Yet bladder cancer research is underfunded relative to other common cancers. As a result, bladder cancer care is prone to evidence gaps that produce decision uncertainty for both patients and clinicians. The Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) for Bladder Cancer Study has the potential to fill these critical evidence gaps, change care pathways for the management of non-muscle-invasive bladder cancer (NMIBC), and provide for personalized, patient-centered care. The purpose of CISTO is to conduct a large prospective study that directly compares the impact of medical management versus bladder removal in recurrent high-grade NMIBC patients with Bacillus Calmette-Guerin (BCG) failure on clinical outcomes and patient and caregiver experience using standardized patient-reported outcomes (PROs).

Sex

All

Minimum age

18 Years

Patient Eligibility, Inclusion Criteria:

1. Adult 18 years of age or older; and
2. Presenting with high-grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1, and with:

   1. Pathology documentation from any hospital/clinic/medical center, and
   2. More than 50% urothelial carcinoma component in the specimen
3. History of high-grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1; and
4. Attempted or received induction BCG (at least 3 out of 6 instillations) at any point in time; and
5. In the previous 12 months, received at least one instillation of any intravesical agent (induction or maintenance) or one administration of systemic therapy for NMIBC treatment.

Patient Eligibility, Exclusion Criteria:

1. Any plasmacytoid or small cell (neuroendocrine) component in the pathology (past or current presentation);
2. Previous history of cystectomy or radiation therapy for bladder cancer;
3. Previous history of muscle-invasive bladder cancer or metastatic bladder cancer;
4. Any history of upper tract urothelial carcinoma;
5. Incarcerated in a detention facility or in police custody (patients wearing a monitoring device can be enrolled) at baseline/screening;
6. Contraindication to radical cystectomy (e.g., American Society of Anesthesiologists (ASA) physical status of 4, patient not considered a radical cystectomy candidate due to comorbidity);
7. Contraindication to medical therapy (i.e., intolerant of all medical therapies);
8. Unable to provide written informed consent in English;
9. Unable to be contacted for research surveys;
10. Planning to participate in a Phase I or Phase II interventional clinical trial for NMIBC (unless in the control/comparator arm of a Phase II trial) or any blinded interventional trial for NMIBC.

• DERIVEDGore JL, Wolff EM, Nash MG, Comstock BA, Gilbert SM, Chang SS, Chisolm S, MacLean DB, Wright JL, Kates MR, Pohar KS, Guzzo TJ, Bivalacqua TJ, Nepple KG, Montgomery JS, Scarpato KR, Woldu SL, Master VA, Chen DYT, Mossanen M, Daneshmand S, O'Neil BB, Tyson MD, Westerman ME, Kamat AM, Mansour AM, Chamie K, Riggs SB, Kukreja JB, Modi PK, Garg T, Peyton CC, Nix JW, Dickstein R, Gadzinski AJ, Sankin A, Shore ND, Lane BR, Bassett JC, Patel S, Morris DS, Macleod LC, Lee EK, Ritch CR, Follmer KM, Lee JR, Kim SM, Kessler LG, Smith AB; CISTO Collaborative group. Twelve-Month Results From the CISTO Study Comparing Radical Cystectomy Versus Bladder-Sparing Therapy for Recurrent High-Grade Non-Muscle-Invasive Bladder Cancer. J Clin Oncol. 2026 Feb;44(4):274-285. doi: 10.1200/JCO-25-01324. Epub 2025 Dec 15. PMID 41397208
• DERIVEDGore JL, Wolff EM, Comstock BA, Follmer KM, Nash MG, Basu A, Chisolm S, MacLean DB, Lee JR, Lotan Y, Porten SP, Steinberg GD, Chang SS, Gilbert SM, Kessler LG, Smith AB; CISTO Collaborative. Protocol of the Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high-grade non-muscle invasive bladder cancer. BMC Cancer. 2023 Nov 18;23(1):1127. doi: 10.1186/s12885-023-11605-8. PMID 37980511