BEST CARE for Recurrent NMIBC: BladdEr-Sparing Therapy and Cystectomy As TREatments

PROJECT SUMMARY/ABSTRACT Bladder cancer is the 6th most common cancer in the US and the 4th most common cancer in males. Each year, more than 80,000 people in the US are diagnosed with bladder cancer and over 17,000 will die. The vast majority (74%) present with non-muscle invasive bladder cancer (NMIBC). NMIBC has the oldest median age

at diagnosis, intensive surveillance requirements, high recurrence and progression rates (up to 80%), and one of the greatest lifetime treatment costs of all cancers. Treatment options following recurrence of high-grade NMIBC include either BST (bladder sparing therapies with significant risk of cancer recurrence and/or

progression) or radical cystectomy (a life-altering bladder removal surgery with substantial short-term morbidity and mortality). However, patients, their caregivers, and clinicians must make this complex treatment decision based on limited evidence since bladder cancer research remains underfunded relative to other common

cancers, bladder cancer epidemiology cohorts are uncommon, RCTs have proven challenging to conduct, and risk stratification models are inadequate. Thus, there is a critical need for high-quality research in recurrent high-grade NMIBC across the full spectrum of outcomes to inform treatment decision-making. A recently

established and unique cohort can be leveraged to address these evidence gaps. Specifically, the PCORI- funded Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) Study is a large pragmatic multisite study of patients with recurrent high-grade NMIBC patients who have selected BST or

radical cystectomy to manage their cancer. The CISTO cohort is a unique resource in bladder cancer care and has potential to serve as the foundation for addressing critical questions relevant to optimal patient-centered management. However, longer-term follow up of the CISTO cohort is required to fully assess the comparative

effectiveness and harms of management options for recurrent high-grade NMIBC. In addition, incorporating molecular factors associated with bladder cancer progression has the potential to improve clinical staging and augment risk prediction models. Finally, the financial impact of new BST options is an important consideration

for patients with what is already one of the most expensive types of cancer to treat. Therefore, we propose the BEST CARE for Recurrent NMIBC study 1) To compare long-term outcomes (clinical and patient- reported) between patients undergoing BST or radical cystectomy, 2) To determine whether prediction

of progression to muscle-invasive or metastatic bladder cancer is improved by molecular staging, and 3) To evaluate the impact of newly approved BST options on financial toxicity. We aim to fill substantial knowledge gaps about long-term oncologic and quality of life (QOL) outcomes, specifically addressing the

continued role of radical cystectomy. If radical cystectomy is associated with better long-term clinical outcomes, less financial hardship, and similar long-term QOL as BST, in the context of additional information offered through molecular staging, this would be impactful to clinical NMIBC practice.