Intermediate-risk Non-muscle-invasive Bladder Cancer: Updated Consensus Definition and Management Recommendations from the International Bladder Cancer Group

Abstract

Context: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease.

Objective: To update the International Bladder Cancer Group (IBCG) guidance and provide practical recommendations on IR NMIBC management.

Evidence acquisition: A collaborative review of published randomized clinical trials, meta-analyses, systematic reviews, and clinical practice guidance on IR NMIBC published before January 2022 was undertaken using PubMed/Medline.

Evidence synthesis: Variation exists between guidelines in defining IR NMIBC. The IBCG recommends defining IR NMIBC as any TaLG tumor that is either recurrent or multifocal or has size ≥3 cm, OR any T1LG tumor. If the 3 tier grading system is used, than any TaG2 tumor would also be considered IR diease regardless of whether new diagnosis or recurrent. Accurate grading and staging of tumor, particularly in ruling out HG/G3 disease and/or carcinoma in situ, are crucial. The IBCG recommends that management of IR NMIBC should be further based on the following risk factors: multifocal tumor (more than one), early recurrence (<1 yr), frequent recurrence (>1/yr), tumor size (≥3 cm), and failure of prior intravesical treatment. Patients with no risk factors are best managed by one dose of postoperative intravesical chemotherapy. Patients with one to two risk factors should be offered additional adjuvant induction intravesical chemotherapy (or bacillus Calmette-Guérin (BCG) if prior chemotherapy has been used). Patients with three or more risk factors should be offered induction plus 1-yr maintenance BCG. Where BCG is not available or recurrent disease following BCG is present, alternative intravesical treatments such as chemotherapy (single agent, combination, or chemohyperthermia) or a clinical trial are recommended.

Conclusions: Standardizing the definition of IR NMIBC is critical for appropriate management of patients and for allowing a comparison of outcomes across clinical trials. The IBCG recommends defining IR NMIBC as any TaLG tumor that is either recurrent or multifocal or ≥3 cm, OR any T1LG tumor. If the 3 tier grading system is used, than any TaG2 tumor would also be considered IR disease regardless of whether new diagnosis or recurrent. Adjunctive management should then be based on established risk factors.

Patient summary: Standardizing the definition of intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC), which is a heterogeneous disease, is critical for appropriate management of patients. The International Bladder Cancer Group recommends classification of IR NMIBC tumors and personalized management based on the following risk factors: multifocal tumor (more than one), early recurrence (<1 yr), frequent recurrence (>1/yr), tumor size (≥3 cm), and previous intravesical treatment.

Keywords: Bacillus Calmette-Guérin; Bladder cancer; Chemotherapy; Guidelines; Intermediate risk; Intravesical.