Patient, caregiver, and provider reported risk-benefit acceptance thresholds in non-muscle invasive bladder cancer (NMIBC) trial designs.
Authors: Hahn Noah M. , Sachse Karen , Schulman David , Sloan Frank , Zipursky Quale Diane , Lotan Yair , Schuckman Anne K. , Porten Sima P. , Dubinski David , Guo Amy , Mahadevia Parthiv , Pietzak Eugene J. , Kamat Ashish M. , Chisolm Stephanie , Stout Morgan , Steinberg Gary D. , Bangs Rick 
Published: March 2021

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Background: FDA guidelines for NMIBC clinical trial design have stimulated a marked increase in NMIBC trial conduct. However, NMIBC patient (PT) input to define acceptable treatment toxicity thresholds and clinical measures most meaningful to NMIBC PTS has been lacking. We conducted a survey to investigate treatment side effect tolerance levels, respondent-ranked clinical relevance of various trial efficacy measures, and differences in responses between PTS, caregivers (CG), and healthcare providers. Methods: In 8/2018, an NMIBC Patient-Driven Endpoints working group was formed at the Bladder Cancer Advocacy Network (BCAN) Think Tank meeting. Through iterative focus groups, a 21-question survey composed of 4 domains (demographics, treatment history, acceptable toxicity thresholds, and clinical benefit metrics) was designed. The BCAN Patient Survey Network and other social media platforms were utilized to distribute and publicize the survey. A unique IP address was required to eliminate duplicate respondents. Categorical and ordinal variables were reported as frequencies with 95% confidence intervals. Continuous variables were reported as medians with ranges. Frequency differences in specific variables of interest according to respondent roles were assessed by Chi-square testing with significance set at p < .05. Results: From 7/18-8/30/20, 845 survey responses were recorded. Key demographics included: 647 (76.7%) PTS, 77 CG (9.1%), 67 urologists (UROL) (7.9%), 35 medical oncologists (ONC) (4.1%), 59.8% male, 85.0% Caucasian non-Hispanic, median age 64.0 years, and 62.7% with NMIBC at diagnosis. Any reversible toxicity was deemed acceptable in 68.8% of PT, 61.0% of CG, 62.7% of UROL, and 54.3% of ONC respondents p = 0.09. Any permanent toxicity was deemed acceptable by 15.6% of PT, 11.7% of CG, 16.4% of UROL, and 20.0% of ONC respondents p = 0.54. Differences in acceptance of individual treatment related toxicities according to roles were observed p < .05 and will be presented. Mean rank order of potential clinical trial endpoints with a rank of 1 for most clinically meaningful benefit to 5 for least meaningful were 1.96 for avoidance of cystectomy, 2.13 for prevention of muscle invasion, 2.87 for 24-month recurrence free survival (RFS), 3.55 for 12-month RFS, and 3.97 for complete response rate with little variation according to respondent roles. Conclusions: Threshold levels for global reversible and permanent treatment toxicity rates were similar across respondent roles. Complete response was consistently ranked lowest in clinical relevance among all respondent roles. These survey results provide important patient and provider benchmarks for acceptable toxicity thresholds within future NMIBC trial designs and suggest an increased emphasis on bladder preservation and durability of response in evaluating the merits of new NMIBC therapies.