Non-muscle-invasive bladder cancer (NMIBC) represents a significant global therapeutic challenge, particularly in the era of Bacillus Calmette-Guérin (BCG) shortage. High-risk NMIBC can progress to muscle invasive or metastatic disease in 25% of patients. Optimal treatment selection, according to risk stratification, is imperative. International guidelines slightly differ in their categorisation of low, intermediate and high-risk NMIBC. Nonetheless, a single post-operative instillation of chemotherapy with Mitomycin C (MMC) or Gemcitabine improves relapse-free survival (RFS) in low-risk NMIBC. Induction and maintenance intravesical BCG remains the historical gold standard for patients with intermediate or high-risk NMIBC. However, clinicians may be forced to consider alternatives given the current BCG shortage. Both intravesical MMC and Gemcitabine have been associated with similar efficacy to BCG, albeit in smaller studies. MMC may also be manipulated using a variety of methods to potentiate its effects. BCG treatment delivery may also be modified without affecting efficacy through dose reduction and abbreviation or omission of maintenance therapy. Preliminary data also highlight that directly proceeding to radical cystectomy may not adversely affect long-term quality of life measures. Access to new systemic and intravesical therapies must be prioritised for patients with BCG recurrent or unresponsive disease. When used in conjunction with molecularly defined biomarkers, these agents herald the potential for improved survival outcomes and alleviation of the current BCG shortage.

Keywords: ADC; Antibody–drug conjugate; BCG; Bacillus Calmette–Guérin; Bladder cancer; Chemotherapy; Immunotherapy; Intravenous; Intravesical; Mitomycin; NMIBC; Non-muscle invasive.