The Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study is a prospective observational cohort study of patients with bladder cancer whose high grade nonmuscle-invasive bladder cancer (NMIBC) has recurred after first-line intravesical bacillus Calmette-Guérin (BCG). CISTO was developed in partnership with the Bladder Cancer Advocacy Network (BCAN) and is led by John Gore from the University of Washington and Angela Smith from the University of North Carolina. CISTO derives from prior work developing and implementing the BCAN Patient Survey Network for patient-centered research prioritization. Planning for the CISTO study design required critical input from patients, community members and researchers such as myself, particularly in determining feasibility and incorporating outcomes important to patients affected by NMIBC that has not responded to BCG (fig. 1).

Figure 1. Illustrative quotes from CISTO stakeholders.

Patients with recurrent high-grade NMIBC face complicated treatment decisions to pursue either further salvage medical therapy or radical cystectomy. Patients weigh tradeoffs such as the risk of progression of bladder cancer and loss of a window of potential cure vs the risk of morbidity and loss of quality of life with radical cystectomy. The results from CISTO will help patients, caregivers and providers to make better informed, individualized treatment decisions by providing real-world evidence about clinical outcomes and downstream quality of life (QOL) in the recurrent high grade NMIBC setting.

To achieve that goal, CISTO is comparing patient-reported and patient-centered clinical outcomes (eg recurrence-free survival) between patients undergoing radical cystectomy and those receiving bladder-sparing medical therapies for NMIBC who have failed first-line BCG (fig. 2). Participants from the BCAN Patient Survey Network were integral to selecting the patient-reported outcomes used in CISTO such as 12-month patient-reported physical functioning measured with the EORTC QLQ-C30 (see table).^1-3 Other measures include self-reported urinary and sexual function measured with the Bladder Cancer Index,⁴ NMIBC treatment preferences, decisional regret, financial distress measured with the Comprehensive Score for Financial Toxicity (COST),⁵ health care utilization measured as 12-month hospital and urology clinic days, return to work/normal activities, 12-month disease-free survival, metastasis-free survival, bladder cancer-specific survival and progression to muscle-invasive bladder cancer. CISTO also seeks to understand patient preferences using health-related QOL metrics and qualitative interviews.

Figure 2. Overview of CISTO study design.

The CISTO trial aims to enroll 900 patients and 25 caregivers, and currently includes 32 sites with diverse geographic locations, community type, size and practice setting. Involving rural community sites such as our site at Geisinger is strategic to ensuring generalizable results from this large pragmatic trial. Enrollment began in July 2019 at the University of Washington, with sites onboarded gradually over the past 2 years. Although the ongoing COVID-19 pandemic has slowed enrollment, implementing remote enrollment at a majority of sites has reduced pandemic-related barriers to recruitment. As of September 2021, a total of 145 patients have been enrolled, with 88 in the medical treatment group and 57 in the radical cystectomy group.

Given the large number of sites, CISTO is overseen by several committees to ensure the study’s success. Several stakeholders convene monthly as part of the executive committee (of which we are members), and weekly meetings occur with members of the data, clinical and stakeholder coordinating centers. These committees oversee the operation of CISTO, provide guidance to sites and research staff, and address any challenges as they arise. The advocate advisory board includes 8 bladder cancer patients and caregivers who ensure that the study maintains a clear patient-centered focus with regard to study conduct and future dissemination of results. All stakeholders meet once per year at our CISTO annual meeting, most recently held virtually on August 6, 2021. Among 82 attendees, we focused on challenges such as increasing enrollment at sites through all-site meetings and case discussions, clarifying inclusion/exclusion criteria, and discussing common barriers (such as exclusion of Phase 2 trials). Continued communication and maintaining a patient-centered focus will allow us to complete enrollment and provide much-needed answers for patients who face this challenging clinical dilemma.

In summary, CISTO is a patient-centered trial at its core: conceived from patient research prioritization, designed with patients who identified patient-centered outcomes and guided by iterative stakeholder input. Enrollment is underway at many sites around the country, and we enthusiastically await results from this important trial to support our patients with recurrent high risk NMIBC.

For any questions about the CISTO study, please visit cistostudy.org or email CISTOPM@uw.edu.