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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Bladder Cancer; Non-muscle Invasive Bladder Cancer; Cancer of the Bladder, Recurrent

Detailed Description

Most bladder cancer patients (74%) present with NMIBC where the cancer is limited to the lining or support layer of the bladder. High-grade NMIBC is treated initially with endoscopic resection and intravesical immunotherapy, followed by bladder instillations of BCG. Most patients with high-risk, high-grade NMIBC are able to retain their bladders and avoid more invasive treatments. However, 24-61% of patients will have their cancers recur within 12 months of treatment with BCG (BCG failures), and they have limited treatment options. National guidelines recommend consideration between two alternatives: additional medical management and radical cystectomy (removal of the bladder). Selecting between these options involves weighing the risk of progression of bladder cancer and loss of a window of potential cure versus the risk of morbidity and loss of quality of life (QOL) with bladder removal. This complex decision-making engages patients and their caregivers, who may be impacted by the urinary, sexual, and bowel dysfunctions that can occur with NMIBC treatment.

The investigators will evaluate this research question on a large scale in real world practice settings including academic and community-based practices and examine patient-centered outcomes. The investigators have engaged stakeholders with diverse perspectives relevant to this research question, including patients, caregivers, national patient advocacy organizations, national medical specialty organizations, guideline developers, health care payers, and industry. By engaging broad expertise relevant to this research question, the investigators will ensure that the study results will help NMIBC patients whose cancer recurs after BCG treatment make more informed decisions that improve the health outcomes that are important to them.

CISTO is an observational study that will not affect the treatment that patients chose. Patient surveys will occur at study entry and at follow-up assessments for up to four years. There will also be a qualitative sub-study that will include interviews of approximately 50 patients and 25 caregivers recruited from the observational cohort study.

• Study Type: Observational
• Enrollment (Actual): 570

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Cancer Center
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive CA Center
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • LSU Healthcare Network - Multi Specialty Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University, School of Medicine
    • Hanover, Maryland, United States, 21076
      • Chesapeake Urology Research Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine Rogel Cancer Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
    • Royal Oak, Michigan, United States, 48073
      • Comprehensive Urology -- A Division of Michigan Healthcare Professionals
  • New York
    • The Bronx, New York, United States, 10461
      • Albert Einstein College Of Medicine
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73114
      • Stephenson Cancer Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Asante Rogue Regional Medical Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19122
      • Perelman Center for Advanced Medicine
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center, LLC
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37209
      • Urology Associates, P.C.
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center at San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (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 second-line treatment will be approached for participation in this observational study in addition to their caregivers. Enrollment at each site will aim for a 2:1 ratio of participants selecting bladder-sparing therapy to radical cystectomy in order to ensure adequate enrollment of radical cystectomy patients. There will also be a qualitative sub-study that will include interviews of 50 patients and 25 caregivers recruited from the observational cohort study.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	The primary outcome of 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 in order to be calculated.	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 in order to be calculated.	24 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 in order to be calculated.	60 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Self-reported Urinary Health as Measured by the Bladder Cancer Index Urinary Summary Score	The evaluation of the effect of treatment choice on patient-reported urinary health, as 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 Self-reported Urinary Health as Measured by the Bladder Cancer Index Urinary Summary Score	The evaluation of the effect of treatment choice on patient-reported urinary health, as 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.	24 months after enrollment
Patient Self-reported Urinary Health as Measured by the Bladder Cancer Index Urinary Summary Score	The evaluation of the effect of treatment choice on patient-reported urinary health, as 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.	60 months after enrollment
Patient Self-reported Sexual Health as Measured by the Bladder Cancer Index Sexual Summary Score	The evaluation of the effect of treatment choice on patient-reported sexual health, as 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 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 Self-reported Sexual Health as Measured by the Bladder Cancer Index Sexual Summary Score	The evaluation of the effect of treatment choice on patient-reported sexual health, as 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 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.	24 months after enrollment
Patient Self-reported Sexual Health as Measured by the Bladder Cancer Index Sexual Summary Score	The evaluation of the effect of treatment choice on patient-reported sexual health, as 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 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.	60 months after enrollment
Patient Self-reported Bowel Health as Measured by the Bladder Cancer Index Bowel Summary Score	The evaluation of the effect of treatment choice on patient-reported bowel health, as 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 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 Self-reported Bowel Health as Measured by the Bladder Cancer Index Bowel Summary Score	The evaluation of the effect of treatment choice on patient-reported bowel health, as 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 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.	24 months after enrollment
Patient Self-reported Bowel Health as Measured by the Bladder Cancer Index Bowel Summary Score	The evaluation of the effect of treatment choice on patient-reported bowel health, as 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 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.	60 months after enrollment
Patient Self-reported Financial Distress as Measured by the Comprehensive Score for Financial Toxicity (COST)	The evaluation of the effect of treatment choice on patient-reported financial distress, as measured by the Comprehensive Score for Financial Toxicity (COST). The COST 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 greater financial wellbeing. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated. Item nonresponse is accounted for by substituting the mean of the completed items in the subscale.	12 months after enrollment
Patient Self-reported Financial Distress as Measured by the Comprehensive Score for Financial Toxicity (COST)	The evaluation of the effect of treatment choice on patient-reported financial distress, as measured by the Comprehensive Score for Financial Toxicity (COST). The COST 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 greater financial wellbeing. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated. Item nonresponse is accounted for by substituting the mean of the completed items in the subscale.	24 months after enrollment
Patient Self-reported Financial Distress as Measured by the Comprehensive Score for Financial Toxicity (COST)	The evaluation of the effect of treatment choice on patient-reported financial distress, as measured by the Comprehensive Score for Financial Toxicity (COST). The COST 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 greater financial wellbeing. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated. Item nonresponse is accounted for by substituting the mean of the completed items in the subscale.	60 months after enrollment
Patient-reported Anxiety as Measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Anxiety 4a	The evaluation of patient-reported anxiety, as measured by the Patient Reported Outcome Measurement Information System (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 Anxiety as Measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Anxiety 4a	The evaluation of patient-reported anxiety, as measured by the Patient Reported Outcome Measurement Information System (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.	24 months after enrollment
Patient-reported Anxiety as Measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Anxiety 4a	The evaluation of patient-reported anxiety, as measured by the Patient Reported Outcome Measurement Information System (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.	60 months after enrollment
Patient-reported Depression as Measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Depression 4a	The evaluation of patient-reported depression, as measured by the Patient Reported Outcome Measurement Information System (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 Depression as Measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Depression 4a	The evaluation of patient-reported depression, as measured by the Patient Reported Outcome Measurement Information System (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.	24 months after enrollment
Patient-reported Depression as Measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Depression 4a	The evaluation of patient-reported depression, as measured by the Patient Reported Outcome Measurement Information System (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.	60 months after enrollment
Patient-reported Generic Quality of Life as Measured by the EuroQoL EQ-5D-5L	The evaluation of patient-reported generic quality of life as measured by the EuroQoL EQ-5D-5L (EQ-5D). Scores range from 0 to 1, with higher scores indicating better health.	12 months after enrollment
Patient-reported Generic Quality of Life as Measured by the EuroQoL EQ-5D-5L	The evaluation of patient-reported generic quality of life as measured by the EuroQoL EQ-5D-5L (EQ-5D). Scores range from 0 to 1, with higher scores indicating better health.	24 months after enrollment
Patient-reported Generic Quality of Life as Measured by the EuroQoL EQ-5D-5L	The evaluation of patient-reported generic quality of life as measured by the EuroQoL EQ-5D-5L (EQ-5D). Scores range from 0 to 1, with higher scores indicating better health.	60 months after enrollment
Patient Recurrence-free Survival	The evaluation of the effect of treatment choice on recurrence-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (recurrence or death). A recurrence was defined as any subsequent episode of high-grade bladder cancer in the bladder or elsewhere in the urinary tract (penile urethra, prostatic urethra, ureters, renal pelvis), either non-muscle or muscle invasive bladder cancer (for cystectomy arm this excludes any finding at cystectomy). Censoring occurred 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 Recurrence-free Survival	The evaluation of the effect of treatment choice on recurrence-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (recurrence or death). A recurrence was defined as any subsequent episode of high-grade bladder cancer in the bladder or elsewhere in the urinary tract (penile urethra, prostatic urethra, ureters, renal pelvis), either non-muscle or muscle invasive bladder cancer (for cystectomy arm this excludes any finding at cystectomy). Censoring occurred at the last electronic health record review or death.	24 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Recurrence-free Survival	The evaluation of the effect of treatment choice on recurrence-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (recurrence or death). A recurrence was defined as any subsequent episode of high-grade bladder cancer in the bladder or elsewhere in the urinary tract (penile urethra, prostatic urethra, ureters, renal pelvis), either non-muscle or muscle invasive bladder cancer (for cystectomy arm this excludes any finding at cystectomy). Censoring occurred at the last electronic health record review or death.	60 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Metastasis-free Survival	The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A metastasis was defined as metastasis to distant lymph/nodes organs (pathologic or radiologic diagnosis of M+ disease) (for cystectomy arm this includes findings at cystectomy). Censoring occurred 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 Metastasis-free Survival	The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A metastasis was defined as metastasis to distant lymph/nodes organs (pathologic or radiologic diagnosis of M+ disease) (for cystectomy arm this includes findings at cystectomy). Censoring occurred at the last electronic health record review or death.	24 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Metastasis-free Survival	The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A metastasis was defined as metastasis to distant lymph/nodes organs (pathologic or radiologic diagnosis of M+ disease) (for cystectomy arm this includes findings at cystectomy). Censoring occurred at the last electronic health record review or death.	60 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Progression-free Survival	The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A progression was 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 occurred 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 Progression-free Survival	The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A progression was 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 occurred at the last electronic health record review or death.	24 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Progression-free Survival	The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A progression was 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 occurred at the last electronic health record review or death.	60 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Bladder Cancer-specific Survival	The evaluation of the effect of treatment choice on bladder cancer-specific survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death from bladder cancer). Censoring occurred 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
Patient Bladder Cancer-specific Survival	The evaluation of the effect of treatment choice on bladder cancer-specific survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death from bladder cancer). Censoring occurred at the last electronic health record review or date of death from bladder cancer.	24 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Bladder Cancer-specific Survival	The evaluation of the effect of treatment choice on bladder cancer-specific survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death from bladder cancer). Censoring occurred at the last electronic health record review or date of death from bladder cancer.	60 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Overall Survival	The evaluation of the effect of treatment choice on overall survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death). Censoring occurred at the last electronic health record review or date of death.	12 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer, up to 12 months post enrollment
Patient Overall Survival	The evaluation of the effect of treatment choice on overall survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death). Censoring occurred at the last electronic health record review or date of death.	24 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer
Patient Overall Survival	The evaluation of the effect of treatment choice on overall survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death). Censoring occurred at the last electronic health record review or date of death.	60 months after diagnosis of recurrent high-grade non-muscle invasive bladder cancer

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: John L Gore, MD, University of Washington

Publications and helpful links

General Publications

• Gore 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.
• Gore 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2019
• Primary Completion (Actual): January 31, 2025
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: April 19, 2019
• First Submitted That Met QC Criteria: April 28, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: caregivers; neoplasms by site; neoplasms; pragmatic trial; radical cystectomy; physiological effects of drugs; Bacillus Calmette-Guerin (BCG); urinary bladder neoplasms; urogenital neoplasms; urinary bladder disease; immunologic factors; immunologic adjuvants; urologic diseases
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Pathological Conditions, Signs and Symptoms; Non-Muscle Invasive Bladder Neoplasms; Neoplasms; Recurrence; Urologic Diseases; Urinary Bladder Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urinary Bladder Diseases
• Other Study ID Numbers: SITE00001017; PCS-2017C3-9380 (Other Identifier: PCORI); RG1121143 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2020-06082 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified study data will be shared according to the PCORI policy for data management and data sharing.
• IPD Sharing Time Frame: The PCORI-designated repository will make the data available for third-party requests when PCORI makes the Final Research Report available on the PCORI website pursuant to PCORI's Process for Peer Review of Primary Research and Public Release of Research Findings. Data will be available in perpetuity.
• IPD Sharing Access Criteria: Individual investigators or teams of investigators seeking access to data from PCORI-funded studies must complete and submit a data request form to the PCORI-designated repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No