Clinical Outcomes in Bacillus Calmette-Guérin-Exposed Non-Muscle-Invasive Bladder Cancer.

Importance: Bacillus Calmette-Guérin (BCG) therapy is the standard of care for non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence and progression, and clinical adherence to recommended regimens is low. Objective: To examine the clinical burden, treatment patterns, and outcomes of patients with BCG-exposed NMIBC in the US. Design, Setting, and Participants: This retrospective cohort study examined Optum's deidentified Market Clarity Data (Optum Market Clarity), linking US electronic health records and insurance claims from January 1, 2007, to June 30, 2024. Eligible patients were identified by diagnostic codes consistent with bladder cancer and were required to have received at least 1 full course of BCG. Subgroups were defined by adequacy of induction and maintenance therapy. Exposure: Bacillus Calmette-Guérin therapy classified as adequate or inadequate induction and maintenance according to regulatory definitions. Main Outcomes and Measures: The primary outcome was recurrence within 24 months. Secondary outcomes were progression and cystectomy, and survival was an exploratory outcome. Rates of recurrence, progression, and radical cystectomy were compared between patients with BCG-exposed and BCG-unresponsive NMIBC. Results: The study included 26 876 patients with NMIBC (median [IQR] age at BCG initiation, 73 [65-77] years; 79.5% male), including 9639 patients with carcinoma in situ; baseline demographic and clinical characteristics were similar across induction and maintenance subgroups. Adequate BCG maintenance therapy was uncommon; only 24.9% (4951 of 19 889) of patients across all risk groups received maintenance therapy. Of 5271 patients with carcinoma in situ-containing tumors and sufficient follow-up, 3134 (59.3%) experienced recurrence within 24 months, of whom 2604 (83.1%) were BCG exposed and 530 (16.9%) were BCG unresponsive. Among patients with recurrence, those who were BCG exposed accounted for 83.0% (366 of 441) of disease progression and 87.8% (337 of 384) of cystectomy cases. Most patients with BCG-exposed NMIBC (2442 [93.8%]) had received inadequate maintenance therapy, and progression and cystectomy outcomes were disproportionately concentrated among those with incomplete BCG exposure (330 of 366 [90.2%] and 327 of 337 [97.0%], respectively). Conclusions and Relevance: This retrospective cohort study found that patients with BCG-exposed NMIBC represented a large, underserved population and the majority of those who experienced progression and cystectomy. These findings highlight an urgent need for new therapeutic strategies and clinical trial designs targeting this group.