Maintenance intravesical bacillus Calmette‐Guérin instillation for Ta, T1 cancer and carcinoma in situ of the bladder: Randomized controlled trial by the BCG Tokyo Strain Study Group

Abstract

Objectives:We carried out a prospective, randomized , controlled trial to investigate the efficacy and safety of both induction and maintenance therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) for high-risk non-muscle invasive bladder cancer (NMIBC). Methods: Intravesical instillation of 80 mg Tokyo strain was given to patients with high-risk NMIBC, including carcinoma in situ (CIS), once weekly for eight consecutive weeks as induction therapy. Patients who achieved complete response (CR) were randomly assigned to either the maintenance group or the observation group. Results: A total of 90 patients were enrolled. After induction therapy, 75% of the patients achieved CR and 53 of them were enrolled in the randomized comparative phase. A total of four maintenance instillations were given. Median follow-up was 26.5 and 28.7 months after randomization in the maintenance and the observation group, respectively. Although it was not statistically significant, the 2-year recurrence-free survival rate in the maintenance group (95.8%) was higher than that in the observation group (74.1%, P = 0.078). Univariate analysis identified maintenance therapy as a significant factor influencing recurrence. During induction therapy, 82.2% of patients experienced urination-related adverse drug reactions, but most events were not serious. There were fewer adverse drug reactions with maintenance therapy than with induction therapy. Neither induction therapy nor maintenance therapy reduced patients' quality of life (QOL). Conclusions: These findings show high levels of efficacy and safety of BCG induction treatment for high-risk NMIBC, and suggest that the number of maintenance instillations could probably be reduced without reducing treatment efficacy or influencing QOL.

Monthly intravesical bacillus Calmette-Guérin maintenance therapy for non-muscle-invasive bladder cancer: 10-year experience in a single institute

“…The patients were followed up every 3 months during the first 2 years, and every 6 months thereafter (14). End-points were RFS and progression-free survival (PFS).…”

“…The inclusion criteria were high-risk NMIBC and recurrent NMIBC, such as, pathologically confirmed Ta, T1 and CIS of the bladder, administration of intravesical initiation or maintenance immunotherapy, performance status of 0-2, ability to undergo cystoscopy and TUR-BT, and intact function of main organs (14). Exclusion criteria included reduced dosage of BCG Tice strain, failure of consecutive treatment, strongly positive tuberculin test, history of intravesical BCG instillation, severe bladder irritation before the start of BCG administration and active serious medical complications.…”

A 2-week Maintenance Regimen of Intravesical Instillation of Bacillus Calmette-Guerin is Safe, Adherent and Effective in Patients with Non-muscle-invasive Bladder Cancer: A Prospective, Multicenter Phase II Clinical Trial

“…Saint et al (17) similarly demonstrated that the maintenance therapy reported on by Lamm et al (6) for NMIC yielded a significant reduction in recurrence, but adherence was hindered by adverse reactions: 81% of the patients discontinued the treatment. In Koga et al (18), the number of maintenance instillations was set at four. Maintenance consisting of just four instillations decreased the recurrence rate, compared with induction alone, although this study failed to show significant superiority of the four-instillation maintenance schedule without serious adverse events.…”

Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer

“…13 Five RCTs com pared non3week maintenance schedules to BCG induction only (Table 1). [14][15][16][17][18] None of these alternative maintenance schedules showed a statistically significant reduction in recurrence (range -4% to 22%, average 7%). By contrast, two studies that compared 3week mainten ance to induction treatment alone showed a statistically significant 28% reduction in tumour recur rence (Table 2).…”