AUA 2019: Engaging Stakeholders in Urologic Research: The Patient-Centered Design of a Pragmatic Clinical Trial in Bladder Cancer

Chicago, IL ( Patients are an underrepresented stakeholder in the research process. Dr. John Gore and his group including Dr. Angela Smith partnered with the Bladder Cancer Advocacy Network (BCAN) to develop the Patient Survey Network (PSN) for patient-centered research prioritization. The results of this initiative highlighted the need for comparative effectiveness research studies among patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).  Based on these results, Dr. Gore and Dr. Smith constructed a research design for a trial entitled Comparison of Intravesical therapy and Surgery as Treatment Options (CISTO). Dr. Gore presented the trial design and input from individuals with bladder cancer and their caregivers via a survey distributed to the BCAN PSN designed to query attitudes about randomization, study design, and relevant patient-centered outcomes. 

Their team conducted a web-based survey of the 1,300-member BCAN PSN and responses were collected between March 6, 2017, and April 6, 2017. The survey included questions about bladder cancer diagnosis and treatment history, willingness to participate in clinical trials with different study designs, and the relative importance of various outcomes.

A total of 291 individuals previously diagnosed with bladder cancer responded, 201 of whom reported having had NMIBC, and 104 of whom had experienced recurrent NMIBC after BCG treatment. Among all respondents and within the subgroup of patients who experienced recurrent NMIBC after BCG, only 11% reported being willing to consent to randomization for a study of radical cystectomy versus intravesical therapy. The majority (76%) of patients indicated a strong preference to keep their bladders. Based on these survey results, a randomized trial was deemed not feasible and thus a prospective observational cohort study was selected as the highest quality, most feasible and inclusive study design. Respondents recommended that the most relevant domains with which to compare our two treatments were survival and QOL, ranked in order of:

  1. Overall survival
  2. Risk of spread of the cancer to other parts of the body
  3. Overall quality of life
  4. Impact of the treatments on their caregiver or loved one
  5. Urinary quality of life
  6. The costs or financial distress these treatments can incur
The design of CISTO is to enroll patients with BCG failure NMIBC (unresponsive, relapsing or intolerant) and allow the patient to choose either radical cystectomy or bladder-sparing therapy (intravesical therapy, immunotherapy) in an observational, pragmatic trial design. The primary outcome is a 12-month generic health-related quality of life. Secondary outcomes include (i) bladder cancer-specific survival, (ii) cystectomy, (iii) urinary quality of life, (iv) decision regret, (v) financial toxicity, and (vi) health care use.

AUA 2019 CISTO study design

The CISTO analysis plan is to use targeted maximum likelihood estimation (TMLE) in an attempt to account for unmeasured confounders and use propensity scores as a secondary analysis.

AUA 2019 CISTO analysis plan

Dr. Gore concluded noting that patient input from the BCAN PSN informed the design of a patient-centered pragmatic trial for bladder cancer. These results highlight the importance of involving patients throughout the research process in order to construct feasible study designs whose results will be important to the affected patients.

Presented by: John L. Gore, MD, MS, FACS, is an Associate Professor in Urology, University of Washington, Seattle, Washington

Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia, @zklaassen_md at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois