Risk Stratification in Non-Muscle-Invasive Bladder Cancer in the Era of Expanding Therapeutic Options: Are Current Classifications Still Adequate?

BACKGROUND: NMIBC risk classifications from AFU, EAU, AUA/SUO and NCCN were derived decades ago to estimate recurrence and progression, but the therapeutic landscape has since expanded, gene therapy, an IL-15 superagonist, systemic immunotherapy, and BCG-combination regimens, raising the question of whether these classifications remain adequate to guide treatment selection. OBJECTIVE: To determine whether contemporary NMIBC risk classifications remain adequate for treatment selection, or function as prognostic instruments applied beyond their original purpose. DATA SOURCES: PubMed/MEDLINE, AFU/EAU/AUA-SUO/NCCN guideline portals, FDA/EMA databases, and ClinicalTrials.gov, searched from January 2000 to August 2026. STUDY SELECTION: Narrative review prioritizing original derivation and validation studies of risk models, pivotal randomized trials, and current guideline texts over secondary or conference-only sources, flagged as such throughout. RESULTS: AFU, EAU, AUA/SUO and NCCN diverge architecturally, producing discordant classifications for identical patients, most sharply for low-burden Ta high-grade disease and T1 disease with concomitant CIS. Four agents now hold FDA approval for BCG-unresponsive disease, and two of three recent phase III trials in BCG-naive high-risk disease (CREST, POTOMAC) were positive, but eligibility depends on treatment-exposure definitions outside baseline risk labels; real-world adherence to adequate BCG is below 50%. MRI/VI-RADS shows strong accuracy for muscle invasion but remains unvalidated for risk stratification. We propose a seven-axis, treatment-oriented framework, reassessed at clinical checkpoints, illustrated with two worked examples. LIMITATIONS: Narrative, not systematic, review; some evidence is conference-sourced pending peer-reviewed publication, and the framework is not yet validated. CONCLUSION: Current classifications remain necessary but insufficient alone; treatment selection increasingly requires a dynamic, multi-axial framework reassessed at defined checkpoints rather than fixed at diagnosis.