Long-Term Intravesical Adjuvant Chemotherapy Further Reduces Recurrence Rate Compared with Short-Term Intravesical Chemotherapy and Short-Term Therapy with Bacillus Calmette-Guérin (BCG) in Patients with Non–Muscle-Invasive Bladder Carcinoma

• Published in: European urology 2007-10, Vol.52 (4), p.1123-1130
• Main Authors: Friedrich, Martin G, Pichlmeier, Uwe, Schwaibold, Hartwig, Conrad, Stefan, Huland, Hartwig
• Format: Article
• Language: English
• Subjects: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; BCG Vaccine - administration & dosage; BCG Vaccine - therapeutic use; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - mortality; Carcinoma, Transitional Cell - pathology; Disease-Free Survival; Drug Administration Schedule; Humans; Middle Aged; Mitomycin - administration & dosage; Mitomycin - therapeutic use; Neoplasm Invasiveness; Neoplasm Recurrence, Local - epidemiology; Neoplasm Staging; Regression Analysis; Survival Analysis; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Urology
• ISSN: 0302-2838
• DOI: 10.1016/j.eururo.2007.02.063

Abstract Objective We present a randomised, parallel group, multicentre phase 4 trial comparing short- and long-term chemoprophylaxis with Mitomycin C (MMC) with short-term immunoprophylaxis with Bacillus Calmette-Guérin (BCG) after transurethral resection of the bladder for non–muscle-invasive bladder carcinoma. Methods Four hundred ninety-five patients with intermediate- to high-risk non–muscle-invasive bladder cancer (recurrent and/or multifocal pTaG1, TaG2–3, and T1G1–3) were randomised to BCG RIVM 2 × 108 CFU weekly for 6 wk, MMC 20 mg weekly for 6 wk, or MMC 20 mg weekly for 6 wk followed by monthly instillations for 3 yr. Results The 3-yr recurrence-free rates were 65.5% (95%CI, 55.9–73.5%) for short-term BCG, and 68.6% (59.9–75.7%) for short-term MMC, whereas recurrence-free rates were significantly increased to 86.1% (77.9–91.4%) in patients with MMC long-term therapy (log-rank test, p = 0.001). Conclusions Long-term MMC significantly reduced the risk of tumour recurrence without enhanced toxicity compared with both short-term BCG and MMC in patients with intermediate- and high-risk non–muscle-invasive bladder carcinoma. Our data provide a rationale for maintenance intravesical chemotherapy in this population.