Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer 2 (CISTO2)

Bladder cancer is the most common urinary tract cancer and the 6th most common cancer in the US. 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 for Bladder Cancer Study 2 (CISTO2) has the potential to fill these critical evidence gaps, change care pathways for the management of NMIBC (non-muscle-invasive bladder cancer), and provide for personalized, patient-centered care. The purpose of CISTO2 is to conduct a large prospective study that directly compares the impact of bladder sparing therapies versus bladder removal in recurrent high-grade NMIBC patients on financial toxicity, clinical outcomes and patient and caregiver experience using standardized patient-reported outcomes (PROs).

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer; Recurrent Bladder Cancer; Non-muscle Invasive Bladder Cancer (NMIBC)

• Study Type: Observational
• Enrollment (Estimated): 408

Contacts and Locations

• Study Contact: Name: Sung Min Kim; Phone Number: 206-210-4040; Email: cistorc@uw.edu

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • H. Lee Moffitt Cancer Center & Research Institute
      • Principal Investigator: Scott M Gilbert, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Principal Investigator: Kenneth G Nepple, MD
      • Contact: Francesca Nugent; Phone Number: 319-467-5833; Email: francesca-nugent@uiowa.edu
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Not yet recruiting
      • University of North Carolina
      • Principal Investigator: Angela Smith, MD, MS
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
      • The Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Kristen Scarpato, MD
      • Contact: Darlene Hancock; Phone Number: 615-322-4063; Email: darlene.hancock@vumc.org
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Contact: Sung Min Kim; Phone Number: 206-210-4040; Email: cistorc@uw.edu
      • Principal Investigator: John L Gore, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of recurrent high-grade NMIBC who are considering their next treatment will be approached for participation in this observational study in addition to their caregivers.

Description

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
   2. More than 50% urothelial carcinoma component in the specimen; and
3. History of high-grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1; and
4. 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.

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. Untreated or current urinary tract urothelial carcinoma outside of the bladder (e.g. ureters, renal pelvis, penile urethra for males, urethra for females). Urinary tract cancer outside of the bladder treated more than 2 years ago is not an exclusion;
5. Incarcerated in a detention facility or in police custody at baseline/screening (patients wearing a monitoring device can be enrolled);
6. Contraindication to radical cystectomy (e.g., ASA of 4, patient not considered a radical cystectomy candidate due to comorbidity);
7. Contraindication to BST (i.e., intolerant of all intravesical and intravenous 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 blinded interventional clinical trial for NMIBC such that details about treatment or therapy received will be unavailable for data collection.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Patients who have selected radical cystectomy; Patients with a diagnosis of recurrent high-grade NMIBC who have selected radical cystectomy
Patients who have selected bladder-sparing therapy; Patients with a diagnosis of recurrent high-grade NMIBC who have selected bladder-sparing therapy (BST)
Caregivers of patients who have selected radical cystectomy; Caregivers of patients with a diagnosis of recurrent high-grade NMIBC who have selected radical cystectomy
Caregivers of patients who have selected bladder-sparing therapy; Caregivers of patients with a diagnosis of recurrent high-grade NMIBC who have selected bladder-sparing therapy (BST)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported financial toxicity as measured by the COmprehensive Score for financial Toxicity (COST)	The primary outcome of patient-reported financial toxicity is measured by the COST measure. The questionnaire consists of 11 items, each scored on a 5-point Likert scale from zero to four. After reversing some items as indicated in the scoring manual (by reversing the sign on the original zero to four score and adding four), all item response scores are summed into a single financial toxicity score ranging from 0 to 44, with higher scores indicating less financial toxicity. Item nonresponse is accounted for by summing the items answered, multiplying by the total number of items in the scale, and then dividing by the number of items that were actually answered.	12 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported financial toxicity as measured by the COmprehensive Score for financial Toxicity (COST)	Patient-reported financial toxicity is measured by the COST measure. The questionnaire consists of 11 items, each scored on a 5-point Likert scale from zero to four. After reversing some items as indicated in the scoring manual (by reversing the sign on the original zero to four score and adding four), all item response scores are summed into a single financial toxicity score ranging from 0 to 44, with higher scores indicating less financial toxicity. Item nonresponse is accounted for by summing the items answered, multiplying by the total number of items in the scale, and then dividing by the number of items that were actually answered.	24 months after enrollment
Caregiver self-reported financial distress as measured by the modified Comprehensive Score for Financial Toxicity (COST)	Caregiver-reported financial toxicity is measured by the COST measure. The questionnaire consists of 12 items, each scored on a 5-point Likert scale from zero to four. After reversing some items as indicated in the scoring manual (by reversing the sign on the original zero to four score and adding four), all item response scores are summed into a single financial toxicity score ranging from 0 to 44, with higher scores indicating less financial toxicity. Item nonresponse is accounted for by summing the items answered, multiplying by the total number of items in the scale, and then dividing by the number of items that were actually answered.	12 months after enrollment
Patient self-reported financial well-being as measured by the Consumer Financial Protection Bureau (CFPB) Financial Well-Being Scale	Patient-reported financial well-being is measured by the CFPB financial well-being scale. The scale consists of 10 items plus 2 questions to assist with scoring. Total response values are converted into an overall financial well-being score between 0 to 100, with higher scores indicating better financial wellness. The financial well-being scores vary based on age and how the questionnaire was administered.	12 months after enrollment
Caregiver self-reported financial well-being as measured by the Consumer Financial Protection Bureau (CFPB) Financial Well-Being Scale	Caregiver-reported financial well-being is measured by the CFPB financial well-being scale. The scale consists of 10 items plus 2 questions to assist with scoring. Total response values are converted into an overall financial well-being score between 0 to 100, with higher scores indicating better financial wellness. The financial well-being scores vary based on age and how the questionnaire was administered.	12 months after enrollment
Caregiver self-reported quality of life as measured by the CareGiver Oncology Quality of Life questionnaire (CarGOQol)	Caregiver-reported quality of life is measured by the CarGOQol questionnaire. The CarGOQol consists of 29 items, with 5-point Likert response scales, covering 10 domains. The scores for each domain are obtained by calculating the average item score for that domain. The overall score is calculated as the average of the domain scores. A domain score is calculated when more than half of the questions are answered. All domain scores and the overall score are linearly transformed and moralized using a scale of 0 to 100. Higher scores indicate better quality of life for the caregiver.	12 months after enrollment
Patient-reported quality of life as measured by the Physical Function scale of the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30)	Patient-reported quality of life is measured by the EORTC QLQ-C30 Physical Function scale. The scale ranges in score from 0 to 100, with higher function scores indicating better health. Scale score is calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Each scale requires responses for at least 50% of the items to be calculated.	12 months after enrollment
Patient self-reported urinary health as measured by the Bladder Cancer Index urinary summary score	Patient-reported urinary health is measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate the two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.	12 months after enrollment
Patient-reported anxiety as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Anxiety 4a	Patient-reported anxiety is measured by the PROMIS Short Form v1.0 - Anxiety 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.	12 months after enrollment
Patient-reported depression as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Depression 4a	Patient-reported depression is measured by the PROMIS Short Form v1.0 - Depression 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.	12 months after enrollment
Caregiver-reported anxiety as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Anxiety 4a	Caregiver-reported anxiety is measured by the PROMIS Short Form v1.0 - Anxiety 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.	12 months after enrollment
Caregiver-reported depression as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Depression 4a	Caregiver-reported depression is measured by the PROMIS Short Form v1.0 - Depression 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.	12 months after enrollment
Patient-reported generic quality of life as measured by the EuroQoL EQ-5D-5L	Patient-reported generic quality of life is measured by the EQ-5D. Scores range from 0 to 1, with higher scores indicating better health.	12 months after enrollment
Caregiver-reported generic quality of life as measured by the EuroQoL EQ-5D-5L	Caregiver-reported generic quality of life is measured by the EQ-5D. Scores range from 0 to 1, with higher scores indicating better health.	12 months after enrollment
Patient progression-free survival	The evaluation of the effect of treatment choice on progression-free survival. Survival times are calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastasis or death). A progression is defined as any subsequent episode of muscle-invasive (T2-T4) disease in the bladder or elsewhere in the urinary tract AND/OR locoregional (true pelvic/common iliac) nodal disease (N+) AND/OR distant metastasis (M+) (for cystectomy arm this includes findings at cystectomy). Censoring occurs at the last electronic health record review or death.	12 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer, up to 12 months post enrollment
Patient bladder cancer-specific survival	The evaluation of the effect of treatment choice on bladder cancer-specific survival. Survival times are calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death from bladder cancer). Censoring occurs at the last electronic health record review or date of death from bladder cancer.	12 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer, up to 12 months post enrollment

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John L Gore, MD, MS, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 3, 2025
• First Submitted That Met QC Criteria: November 3, 2025
• First Posted (Actual): November 5, 2025

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms
• Other Study ID Numbers: RG1126118; R01CA289268 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No