# Modern management of BCG-refractory non-muscle-invasive urothelial carcinoma of the urinary bladder

## TL;DR

This paper reviews treatment options for bladder cancer patients who do not respond to BCG therapy, highlighting new therapies and the ongoing role of surgery.

## Contribution

The paper provides an updated review of emerging therapies for BCG-refractory bladder cancer and evaluates their effectiveness compared to radical cystectomy.

## Key findings

- Emerging therapies like systemic immunotherapy and intravesical treatments show promise for BCG-refractory bladder cancer.
- Complete response rates for these therapies range from 41% to 82%, though radical cystectomy remains the gold standard.
- Many patients are unfit or unwilling for surgery, prompting the need for alternative treatments.

## Abstract

High-risk non-muscle-invasive bladder cancer (NMIBC) is most commonly treated with Bacillus Calmette–Guérin (BCG) as first-line therapy. However, in light of the ongoing BCG shortage in the United States, a significant need exists for alternative treatment options, both in the upfront setting as well as for patients with BCG-refractory disease. While radical cystectomy remains the gold standard for patients with BCG-refractory disease, many patients are unfit or unwilling to undergo this procedure. Several new agents, many with novel mechanisms of action, have been approved or are actively being investigated in this setting.

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There is ample evidence for emerging therapies in BCG-refractory NMIBC including systemic immunotherapy and various intravesical options, such as chemotherapy, gene therapy, and novel drug delivery systems. Radical cystectomy, however, remains the gold standard. Response rates and duration of response vary across treatment modalities, with complete response rates at any time ranging from 41% to 82%. Radical cystectomy should still be recommended to patients with high-risk features given the risks of recurrence, progression, upstaging, and occult lymph node metastases.

While radical cystectomy remains the standard of care for patients with BCG-refractory disease, many patients are unable or unwilling to undergo the procedure. Several novel therapies have been recently approved or are currently being investigated with overall promising early results.