Intravesical Chemotherapy for High-Risk Non-Muscle-Invasive Bladder Cancer Refractory to BCG

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Intravesical Chemotherapy for High-Risk Non-Muscle-Invasive Bladder Cancer Refractory to BCG
Intravesical Chemotherapy for High-Risk Non-Muscle-Invasive Bladder Cancer Refractory to BCG

Approximately 80% of patients with bladder cancer present with non-muscle-invasive disease (NMIBC). Of these, 15 to 25% will eventually develop muscle-invasive bladder cancer, and there are a number of known predictors of progression to invasive disease. These include high grade Ta, T1, or carcinoma in situ (CIS), and patients with any of these types of non-muscle-invasive bladder cancer are classified as high risk. Additionally, muscularis mucosa invasion, lymphovascular invasion, variant histology, and urethral involvement are further risk factors for understaging and/or progression to muscle-invasive cancer.1–3 In general, patients with high-risk NMIBC receive intravesical therapy as first-line treatment, although early radical cystectomy may be employed in many instances, and is associated with improvements in disease-specific survival and quality-of-life years.4–6

Current evidence supports the use of bacillus Calmette-Guerin (BCG) for initial intravesical therapy in patients with high-risk NMIBC. A meta analysis demonstrated the superiority of BCG to mitomycin C (MMC) in the treatment of NMIBC as long as a maintenance regimen was included.7 While the overall response rate to BCG is approximately 50%, up to 68% of patients with CIS respond to intravesical BCG.8 Furthermore, those who experience a recurrence after an initial induction course of BCG may respond to additional BCG. As a result, the definition of BCG failure is complex and divided into four broad categories. BCG refractory denotes a lack of any response to BCG and includes those who progress during therapy. BCG resistance indicates that the cancer has either recurred or persisted as a lower stage or lower grade initially, but is absent six months following the induction cycle of BCG. BCG relapsing disease denotes recurrence after achieving disease-free status, and BCG intolerance reflects an inability to complete the full course of BCG due to adverse side effects.

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