Non-maintenance intravesical Bacillus Calmette-Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study

• Published in: BMC cancer Vol. 21; no. 1; p. 266
• Main Authors: Miyake, Makito, Iida, Kota, Nishimura, Nobutaka, Miyamoto, Tatsuki, Fujimoto, Kiyohide, Tomida, Ryotaro, Matsumoto, Kazumasa, Numakura, Kazuyuki, Inokuchi, Junichi, Morizane, Shuichi, Yoneyama, Takahiro, Matsumura, Yoshiaki, Abe, Takashige, Inoue, Masaharu, Yamada, Takeshi, Terada, Naoki, Hirao, Shuya, Uemura, Motohide, Matsushita, Yuto, Taoka, Rikiya, Kobayashi, Takashi, Kojima, Takahiro, Matsui, Yoshiyuki, Kitamura, Hiroshi, Nishiyama, Hiroyuki
• Format: Journal Article
• Language: English
• Published: England BioMed Central 11-03-2021; BMC
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intravesical; Age; Aged; Aged, 80 and over; Bacillus; Bacillus Calmette-Guérin (BCG); BCG Vaccine - administration & dosage; Bladder cancer; Cancer; Cellular biology; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Induction Chemotherapy - methods; Induction Chemotherapy - statistics & numerical data; Induction therapy; Intravesical therapy; Invasiveness; Japan - epidemiology; Kaplan-Meier Estimate; Landmark analysis; Maintenance Chemotherapy - statistics & numerical data; Male; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - prevention & control; Non-muscle invasive bladder cancer; Patients; Progression-Free Survival; Propensity score matching; Retrospective Studies; Surveillance; Survival; Tumors; Urinary Bladder - immunology; Urinary Bladder - pathology; Urinary bladder neoplasms; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Japan; United States > US; Europe; Non-muscle invasive bladder cancer; Propensity score matching; Intravesical therapy; Bacillus Calmette-Guérin (BCG); Landmark analysis; Urinary bladder neoplasms
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-07966-7

To explore possible solutions to overcome chronic Bacillus Calmette-Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG).
This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000-2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven-/eight-dose iBCG (Group C), 60 (2.2%) received seven-/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan-Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed.
RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts.
Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.