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| Intravesical bacillus Calmette-Guerin (BCG) in treating non-muscle invasive bladder cancer—analysis of adverse effects and effectiveness of two strains of BCG (Danish 1331 and Moscow-I) |
Yuvaraja B. Thyavihally*( ),Preetham Dev,Santosh Waigankar,Abhinav Pednekar,Nevitha Athikari,Abhijit Raut,Archan Khandekar,Naresh Badlani,Ashishkumar Asari
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| Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Andheri West, Mumbai, India |
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Abstract Objective: To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin (BCG) Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer. Methods: Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively, and 114 patients who completed a minimum of 12 months of follow-up were analysed. Patient and tumor characteristics, strain of BCG, adverse effects, and tumor progression were included for analysis. Intravesical BCG was instilled in intermediate- and high-risk patients. Six weeks of induction BCG, followed by three weekly maintenance BCG at 3, 6, 12, 18, and 24 months was advised in high-risk patients. Results: Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain. Patient and tumor characteristics were well balanced between the two groups. The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups, respectively. Adverse events like dropout rate, antitubercular treatment requirement, and need of cystectomy were higher in Moscow-I group (n=31, 67.4%) when compared to Danish 1331 strain (n=33, 48.5%) (p=0.046). On direct comparison between Danish 1331 and Moscow-I strain, there was similar 3-year recurrence-free survival (80.0% vs. 72.9%) and 3-year progression-free survival (96.5% vs. 97.8%). Conclusion: Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival, but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.
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Received: 16 April 2020
Available online: 20 April 2022
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Corresponding Authors:
Yuvaraja B. Thyavihally
E-mail: tb.yuvaraja@gmail.com
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| Variable | BCG Danish 1331
(n=68) | BCG Moscow-I
(n=46) | p-Value | | Sex, n (%) | | Male | 57 (83.8) | 38 (82.6) | 0.864 | | Female | 11 (16.2) | 8 (17.4) | | Age, median (range), year | 60.5 (34.0-78.0) | 61.5 (38.0-77.0) | 0.794 | | Past history of TURBT, n (%) | | Nil | 48 (70.6) | 33 (71.7) | 0.894 | | 1 | 15 (22.1) | 11 (23.9) | | ≥2 | 5 (7.4) | 2 (4.3) | | Tumor status, n (%) | | pTa | 25 (36.8) | 15 (32.6) | 0.735 | | pT1 | 38 (55.9) | 25 (54.3) | | pTis | 3 (4.4) | 4 (8.7) | | pT1+pTis | 2 (2.9) | 2 (4.3) | | Tumor risk stratification, n (%) | | Low | 8 (11.8) | 3 (6.5) | 0.723 | | Intermediate | 33 (48.5) | 24 (52.2) | | High | 27 (39.7) | 19 (41.3) |
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Baseline demographic details and tumor characteristics of patients treated with adjuvant intravesical BCG Danish 1331 and BCG Moscow-I strain for non-muscle invasive bladder cancer.
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| Variable | Danish 1331 strain (n=68) | Moscow-I strain (n=46) | p-Value | | Side effect, n (%) | | Nil to mild | 35 (51.5) | 15 (32.6) | 0.046 | | Moderate to severe | 33 (48.5) | 31 (67.4) | | BCG discontinuation/dose reduction, n (%) | | No | 51 (75) | 26 (56.5) | 0.039 | | Yes | 17 (25) | 20 (43.5) | | Requiring antitubercular therapy, n (%) | | No | 63 (92.6) | 37 (80.4) | 0.051 | | Yes | 5 (7.4) | 9 (19.6) | | Requiring cystectomy for BCG side effect, n (%) | | No | 66 (97.1) | 41 (89.1) | 0.093 | | Yes | 2 (2.9) | 5 (10.9) |
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Toxicity and adverse effects in BCG Danish 1331 and BCG Moscow-I strain groups.
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| Variable | Median survival probability at 3 years, %; (95% CI) | Median survival at 4 years, %; (95% CI) | p-Value | | RFS | | BCG Danish 1331 | 80.0; (75.6-84.4) | 68.2; (63.8-72.6) | 0.397 | | BCG Moscow-I | 72.9; (70.9-74.9) | 59.2; (57.2-61.2) | | PFS | | BCG Danish 1331 | 96.5; (93.0-100.0) | 86.1; (82.5-89.7) | 0.703 | | BCG Moscow-I | 97.8; (96.6-99.0) | 79.5; (78.3-80.7) | | OS | | BCG Danish 1331 | 94.6; (91.6-97.6) | 88.2; (85.2-91.2) | 0.373 | | BCG Moscow-I | 88.9; (87.6-90.2) | 83.5; (82.2-94.8) | | DSS | | BCG Danish 1331 | 98.2; (96.5-99.9) | 94.9; (93.2-96.6) | 0.554 | | BCG Moscow-I | 97.6; (96.8-98.4) | 94.0; (96.8-98.4) |
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Survival probability at 3 years and 4 years in BCG Danish 1331 and BCG Moscow-I strain groups.
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Probability with Kaplan-Meier analysis of recurrence-free survival in patients adequately treated with BCG Danish 1331 strain (black) and BCG Moscow-I strain (grey) for non-muscle invasive bladder cancer. BCG, bacillus Calmette-Guerin.
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Probability with Kaplan-Meier analysis of progression-free survival in patients adequately treated with BCG Danish 1331 strain (black) and BCG Moscow-I strain (grey) for non-muscle invasive bladder cancer. BCG, bacillus Calmette-Guerin.
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Probability with Kaplan-Meier analysis of overall survival in patients adequately treated with BCG Danish 1331 strain (black) and BCG Moscow-I strain (grey) for non-muscle invasive bladder cancer. BCG, bacillus Calmette-Guerin.
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Estimated probability with Kaplan-Meier analysis of disease-specific survival in patients adequately treated with BCG Danish 1331 strain (black) and BCG Moscow-I strain (grey) for non-muscle invasive bladder cancer. BCG, bacillus Calmette-Guerin.
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