Intermediate-risk Non-muscle-invasive Bladder Cancer: Recommendations for Definitions, Risk Stratification, Management Strategies, and Clinical Trial Design from the International Bladder Cancer Group.

Background and objective: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease, and standardized definitions and risk-guided management are critical for appropriate patient care and clinical trial development.

Methods: A global committee of bladder cancer experts developed IR-NMIBC recommendations. Working groups reviewed literature and drafted recommendations, which were voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During an August 2024 meeting, voting results and evidence were presented, and recommendations were refined. Final recommendations achieved >75% agreement.

Key findings and limitations: The IBCG recommends inclusion of only low-grade (LG; G1 and G2) tumors in the IR-NMIBC category, risk stratified using the IBCG IR-NMIBC risk scoring system. Given the relatively indolent course and treatment burden of IR-NMIBC, therapeutic deintensification with active surveillance or office-based ablation is appropriate for select patients. Morbidity related to transurethral resection of a bladder tumor can be mitigated by forgoing restaging resection in completely resected LG tumors and not mandating muscularis propria sampling. Perioperative chemotherapy reduces recurrences, and additional adjuvant intravesical treatment should be risk stratified. Clinical trials evaluating novel IR-NMIBC therapies, including adjuvant and ablative designs, should incorporate patient-reported outcomes and risk-stratified controls. Ablative trials, as proof-of-concept studies for efficacy, require randomized controlled studies in the adjuvant setting to confirm superiority over the standard of care.

Conclusions and clinical implications: The IBCG consensus recommendations provide practical guidance for clinical care and clinical trial design for patients with IR-NMIBC.