Evolving Guidelines: Impact of Gene Therapy and BCG Failure Redefinitions on High-Risk NMIBC Patient Management

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EP: 1.Evolving Guidelines: Impact of Gene Therapy and BCG Failure Redefinitions on High-Risk NMIBC Patient Management

EP: 2.Applying Evidence Standards to Guide Gene Therapy Use in BCG-Unresponsive NMIBC

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Recent updates to American Urological Association (AUA), European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines have significantly evolved the clinical approach to managing high-risk non-muscle invasive bladder cancer (NMIBC), particularly in BCG-unresponsive patients. BCG-unresponsive disease is strictly defined as recurrent carcinoma in situ (CIS) within one year of adequate BCG therapy (five of six induction courses or two of three/two of six second induction courses), or papillary disease recurrence within six months of the last BCG dose. These definitions help identify the highest-risk patients who require advanced treatment strategies.

The guidelines have cautiously shifted toward a more bladder-sparing approach, incorporating FDA-approved therapies like gemcitabine and docetaxel, nadofaragene, nogapendekin and pembrolizumab for BCG-unresponsive CIS. However, these treatments are conditionally recommended only for patients unwilling or unable to undergo radical cystectomy, which remains the gold standard. This conservative approach reflects the understanding that most patients are reluctant to undergo radical cystectomy due to potential loss of sexual and urinary function.

Clinical decision-making has evolved to consider patient preferences and quality of life factors more heavily. For patients with minimal CIS that can be effectively managed with blue light cystoscopy, providers are increasingly willing to try bladder-sparing approaches before subjecting patients to radical surgery. This shift represents a balance between oncologic safety and patient-centered care, acknowledging that the most conservative cancer approach isn’t always the best overall approach for individual patients.