Treatment efficacy and tolerability of intravesical Bacillus Calmette-Guerin (BCG) - RIVM strain: induction and maintenance protocol in high grade and recurrent low grade non-muscle invasive bladder cancer (NMIBC)

BACKGROUND: BCG-RIVM strain was used in many treatment protocols for non-muscle invasive bladder cancer only as induction courses. Cho et al. (Anticancer Res 2012) compared BCG-RIVM induction and 'standard' maintenance (Lamm et al., J Urol. 2000) to mitomycin C. They found no statistically significant differences regarding disease recurrence and progression. The purpose of our study was to determine the efficacy & tolerability of this specific BCG RIVM strain, using six-weekly, induction course and single monthly instillations as maintenance for one year, in high risk recurrent, multifocal low grade and multifocal high grade pTa/pT1, CIS transitional cell carcinoma of bladder. METHODS: From 2003 - 2012, BCG-naive patients treated with intravesical BCG-RIVM for high-risk multifocal NMIBC were identified. Transurethral resection of bladder tumor (TURBT) and re-staging TURBT within six weeks, was done for accurate staging and complete elimination of disease. A six-weekly induction course, started 2-3 weeks after the last TURBT, followed by monthly maintenance protocol for one year. Recurrence, progression, cystectomy free survivals, cancer specific and over-all survival were determined. RESULTS: Sixty evaluable patients - median age 63, median follow-up 3.98 years. Forty-two patients (70%) completed BCG-RIVM treatment as planned. BCG termination was necessary in 18 patients (30%). Recurrence occurred in 16 patients (26.7%) at a median follow-up of 24.2 months while progression occurred in five patients (8.3%) at a median follow-up of 33 months. Recurrence-free survival and progression-free survival rates were 73% and 92% respectively. Cystectomy was performed in seven patients (12%) with a cystectomy-free survival of 88%. There were no cancer specific deaths. Two patients died of other causes (3.3%). The overall survival rate was 97%. CONCLUSIONS: Our study is the first to show the clinical efficacy and tolerability of BCG-RIVM strain in the management of high risk NMIBC when given in a schedule of six-weekly induction with monthly maintenance for one year. Our maintenance protocol, achieved equivalent recurrence-free, progression-free, disease specific survival and overall survival to the reported literature and the more intense three-years South West Oncology Group (SWOG) protocol.