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

Sponsor

University of Washington (Other)

Overall Status

Recruiting

CT.gov ID

NCT03933826

Collaborator

Patient-Centered Outcomes Research Institute (Other)

900

Enrollment

Locations

54.8

Anticipated Duration (Months)

27.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 NMIBC (non-muscle-invasive bladder cancer), 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 BCG (Bacillus Calmette-Guerin) failure on clinical outcomes and patient and caregiver experience using standardized patient-reported outcomes (PROs).

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Cancer of the Bladder, Recurrent Non-muscle Invasive Bladder Cancer

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 Design

Study Type:

Observational

Anticipated Enrollment :

900 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jul 9, 2019

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Jan 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Patients who have selected radical cystectomy Patients with a diagnosis of recurrent high-grade NMIBC that failed first-line BCG and who have selected radical cystectomy as their second-line treatment
Patients who have selected medical management Patients with a diagnosis of recurrent high-grade NMIBC that failed first-line BCG and who have selected medical management as their second-line treatment

Outcome Measures

Primary Outcome Measures

Patient-reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) [12 months after completion of the patient baseline assessment]
The primary evaluation of patient-reported quality of life, as measured by the EORTC QLQ-C30 at 12 months, will be conducted using targeted maximum likelihood estimation (TMLE) analysis. All of the subscales and single-item measures range in score from 0 to 100 and a high scale score represents a higher response level (ranging from 0 = low to 100 = high/healthy level of function; from 0 = low to 100 = high quality-of-life; from 0 = low to 100 = high level of symptomatology/problems). Subscale and global health status scores are each calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated.

Secondary Outcome Measures

Patient-reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) [Up to 48 months after completion of the patient baseline assessment]
The evaluation of the effect of treatment choice on the trajectory of patient-reported quality of life, as measured by the EORTC QLQ-C30 at up to 48 months, will be conducted using both mixed effects and generalized estimating equations (GEE) longitudinal models.
Patient self-reported urinary function as measured by the Bladder Cancer Index [12 months after completion of the patient baseline assessment and up to 48 months]
The evaluation of the effect of treatment choice on patient-reported urinary function, as measured by the Bladder Cancer Index (BCI) at 12 months, will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on the trajectory of urinary function at up to 48 months as measured by the BCI will be conducted using both mixed effects and GEE longitudinal models. 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 and two subscale scores (function and bother) are constructed. 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.
Patient self-reported sexual function as measured by the Bladder Cancer Index [12 months after completion of the patient baseline assessment and up to 48 months]
The evaluation of the effect of treatment choice on patient-reported sexual function, as measured by the BCI at 12 months, will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on the trajectory of sexual function at up to 48 months as measured by the BCI will be conducted using both mixed effects and GEE longitudinal models.
Patient self-reported NMIBC treatment preferences [12 months after completion of the patient baseline assessment]
Patients' generic quality of life as measured in quality adjusted life years (QALY) by a series of time tradeoff (TTO) questions at 12 months post-enrollment will be modeled as a function of patient preferences, as measured by additional TTO items measuring QALY for bladder cancer-related health states, while controlling for patients' baseline quality of life, demographic and clinical characteristics using beta regression, stratified by treatment arm.
Patient self-reported decisional regret [12 months after completion of the patient baseline assessment and up to 48 months]
Patient-reported decisional regret will be measured using three items with 5-point Likert response scales which have been validated in a previous study of prostate cancer patients. These three items will be summed to yield a score from 0 to 12, with higher scores indicating greater regret. The evaluation of the effect of treatment choice on patient-reported decisional regret at 12 months will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient-reported decisional regret at up to 48 months will be conducted using both mixed effects and GEE longitudinal models.
Patient self-reported financial distress as measured by the Comprehensive Score for Financial Toxicity (COST) [12 months after completion of the patient baseline assessment and up to 48 months]
The evaluation of the effect of treatment choice on patient-reported financial distress, as measured by COST at 12-months, will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on the trajectory of patient financial distress at up to 48 months will be conducted using both mixed effects and GEE longitudinal models. 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 toxicity. 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.
Patient self-reported healthcare utilization as measured by hospital and urology clinic days [12 months after completion of the patient baseline assessment and up to 48 months]
The evaluation of the effect of treatment choice on healthcare utilization, as measured by 12-month hospital and urology clinic days, will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on the trajectory of patient healthcare utilization at up to 48 months will be conducted using both mixed effects and GEE longitudinal models.
Patient self-reported return to work/normal activities [12 months after completion of the patient baseline assessment]
The evaluation of the effect of treatment choice on patient self-reported return to work/normal activities will be conducted using TMLE analysis.
Patient disease-free survival [12 months after completion of the patient baseline assessment and up to 48 months]
The evaluation of the effect of treatment choice on patient 12-month disease-free survival will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient disease-free survival at up to 48 months will be conducted using TMLE-based survival analysis.
Patient metastasis-free survival [12 months after completion of the patient baseline assessment and up to 48 months]
The evaluation of the effect of treatment choice on patient 12-month metastasis-free survival will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient metastasis-free survival at up to 48 months will be conducted using TMLE-based survival analysis.
Patient progression to muscle-invasive bladder cancer [12 months after completion of the patient baseline assessment and up to 48 months]
The evaluation of the effect of treatment choice on patient 12-month progression to muscle-invasive bladder cancer will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient progression to muscle-invasive bladder cancer at up to 48 months will be conducted using TMLE-based survival analysis.
Patient bladder cancer-specific survival [12 months after completion of the patient baseline assessment and up to 48 months]
The evaluation of the effect of treatment choice on patient 12-month bladder cancer-specific survival will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient bladder cancer-specific survival at up to 48 months will be conducted using TMLE-based survival analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Patient Eligibility, Inclusion Criteria:

Adult 18 years of age or older; and
Presenting with high-grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1, and with:
Pathology documentation from any hospital/clinic/medical center, and
More than 50% urothelial carcinoma component in the specimen
History of high-grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1; and
Attempted or received induction BCG (at least 3 out of 6 instillations) at any point in time; and
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:

Any plasmacytoid or small cell (neuroendocrine) component in the pathology (past or current presentation);
Previous history of cystectomy or radiation therapy for bladder cancer;
Previous history of muscle-invasive bladder cancer or metastatic bladder cancer;
Any history of upper tract urothelial carcinoma;
Incarcerated in a detention facility or in police custody (patients wearing a monitoring device can be enrolled) at baseline/screening;
Contraindication to radical cystectomy (e.g., ASA of 4);
Contraindication to medical therapy (i.e., intolerant of all medical therapies);
Unable to provide written informed consent in English;
Unable to be contacted for research surveys;
Planning to participate in a Phase I or Phase II interventional clinical trial for NMIBC or any blinded interventional trial for NMIBC.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Mayo Clinic Cancer Center	Phoenix	Arizona	United States	85054
3	USC/Norris Comprehensive CA Center	Los Angeles	California	United States	90033
4	UCLA	Los Angeles	California	United States	90095
5	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
6	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	80045
7	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
8	Emory University	Atlanta	Georgia	United States	30322
9	University of Chicago	Chicago	Illinois	United States	60637
10	University of Iowa	Iowa City	Iowa	United States	52242
11	Louisiana State University	Baton Rouge	Louisiana	United States	70803
12	Johns Hopkins University, School of Medicine	Baltimore	Maryland	United States	21231
13	Chesapeake Urology Research Associates	Hanover	Maryland	United States	21076
14	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
15	Michigan Medicine Rogel Cancer Center	Ann Arbor	Michigan	United States	48109
16	Spectrum Health	Grand Rapids	Michigan	United States	49503
17	Albert Einstein College of Medicine	Bronx	New York	United States	10461
18	Columbia University Medical Center	New York	New York	United States	10032
19	University of North Carolina	Chapel Hill	North Carolina	United States	27599
20	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
21	The Ohio State University	Columbus	Ohio	United States	43210
22	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73114
23	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
24	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
25	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania	United States	19122
26	Carolina Urologic Research Center, LLC	Myrtle Beach	South Carolina	United States	29572
27	Urology Associates, P.C.	Nashville	Tennessee	United States	37209
28	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
29	UT Southwestern Medical Center	Dallas	Texas	United States	75390
30	MD Anderson Cancer Center	Houston	Texas	United States	77030
31	The University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
32	University of Utah	Salt Lake City	Utah	United States	84132
33	University of Washington	Seattle	Washington	United States	98195