Efficacy and tolerance of one‐third full dose bacillus Calmette–Guérin maintenance therapy every 3 months or 6 months: Two‐year results of URO‐BCG‐4 multicenter study

Abstract

Abbreviations & Acronyms Objectives:To assess bacillus Calmette-Guérin maintenance treatment schedule for nonmuscle invasive bladder cancer at 2 years, using one-third of the full dose and fewer instillations every 3 months or 6 months. Methods: This was a prospective, randomized, multicenter study. All patients had an intermediate-or high-risk non-muscle invasive bladder cancer. They received three weekly instillations of one-third dose bacillus Calmette-Guérin every 6 months (group I) and two weekly instillations every 3 months (group II) during 3 years. In the two schedules we assessed efficacy, tolerance, leukocyturia and prostate-specific antigen. Results: No significant difference was observed between the two groups for recurrence at 6, 12 or 18 months. At 2 years, tumor recurrence was observed in 10.9% and muscle invasion in 2.9% of cases. Bacillus Calmette-Guérin tolerance was comparable -the adverse events score was 0.8 in group I and 1 in group II (P = 0.242). No statistical correlation was observed between the adverse events score over 2 years, either for leukocyturia (P = 0.8891) or prostate-specific antigen level (P = 0.7155). Leukocyturia level was not significantly associated with tumor recurrence or progression. Conclusion: One-third dose maintenance bacillus Calmette-Guérin is effective with no impact on tumor recurrence or muscle invasion. Furthermore, there seems to be no difference in tumor response or side-effects between patients receiving two or three maintenance instillations every 3 months or 6 months. In clinical practice, the use of leukocyturia or total prostate-specific antigen levels do not appear to be useful in predicting bacillus CalmetteGuérin toxicity.

Low Dose BCG Infection as a Model for Macrophage Activation Maintaining Cell Viability

“…In support to our data, the use of one-half or one-third of BCG for standard instillation has recently been proposed. A study in NMIBC-patients treated with low dose BCG had lower toxicity and higher quality of life compared with NMIBC-patients instilled with standard-dose [57, 58]. Thus, low dose BCG can be applied to different BCG research fields of interest including mycobacterial infections, cancer immunotherapy, and prevention of autoimmunity and allergies [59].…”

Low-Dose Versus Standard Dose of Bacillus Calmette-Guerin in the Treatment of Nonmuscle Invasive Bladder Cancer

“…Low-dose BCG maintenance regimens with a reduced number of instillations have been investigated in 2 RCT studies; it was found in the reduced instillation group that treatment was effective with no impact on tumor recurrence or progression. 27,28 …”

Safety and Efficacy of Intravesical Bacillus Calmette-Guérin Immunotherapy in Patients with Non-Muscle-Invasive Bladder Cancer Presenting with Asymptomatic Bacteriuria: A Systematic Review

“…Finally, leukocytes, recruited and mi- grated into the bladder during the immunological response to BCG [16] , were postulated to predict the recurrence-free survival [17,18] . However, the URO-BCG-4 study did not confirm these findings [19] .…”