Low-dose versus standard-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials

Purpose: Intravesical BCG (bacille Calmette–Guérin) instillation in patients with non-muscle-invasive bladder cancer decreases the risk for tumor recurrence and progression. After one BCG product was discontinued, a chronic global BCG shortage occurred. We focused on identifying a reduced dose of BC...

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Main Authors: Se Young Choi, Moon Soo Ha, Jung Hoon Kim, Byung Hoon Chi, Jin Wook Kim, In Ho Chang, Tae-Hyoung Kim, Soon Chul Myung
Format: Article
Language:English
Published: Korean Urological Association 2022-03-01
Series:Investigative and Clinical Urology
Subjects:
Online Access:https://www.icurology.org/pdf/10.4111/icu.20210340
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author Se Young Choi
Moon Soo Ha
Jung Hoon Kim
Byung Hoon Chi
Jin Wook Kim
In Ho Chang
Tae-Hyoung Kim
Soon Chul Myung
author_facet Se Young Choi
Moon Soo Ha
Jung Hoon Kim
Byung Hoon Chi
Jin Wook Kim
In Ho Chang
Tae-Hyoung Kim
Soon Chul Myung
author_sort Se Young Choi
collection DOAJ
description Purpose: Intravesical BCG (bacille Calmette–Guérin) instillation in patients with non-muscle-invasive bladder cancer decreases the risk for tumor recurrence and progression. After one BCG product was discontinued, a chronic global BCG shortage occurred. We focused on identifying a reduced dose of BCG that could maintain efficacy and reduce adverse effects. Materials and Methods: We conducted a comprehensive literature search of PubMed, Embase, the Cochrane Library, CINAHL, Web of Science, and Scopus to identify randomized controlled trials through April 2021. The odds ratios (ORs) and 95% confidence intervals (CIs) for the low and standard doses in nine studies were compared. A low dose was defined as a low volume of BCG compared with the standard BCG dose (Armand Frappier, 120 mg; Connaught, 81 mg; Danish 1331, 120 mg; modified Danish 1331, 120 mg; Tokyo 172, 80 mg). Results: The low-dose group experienced aggravated recurrence (OR, 1.45; 95% CI, 1.09–1.94; p=0.01) but similar progression (OR, 1.11; 95% CI, 0.76–1.62; p=0.59), similar cancer-specific survival (OR, 1.02; 95% CI, 0.60–1.75; p=0.93), similar overall survival (OR, 1.09; 95% CI, 0.76–1.56; p=0.65), favorable adverse effects (OR, 0.41; 95% CI, 0.28–0.62; p<0.0001), and favorable withdrawal (OR, 0.42; 95% CI, 0.25–0.71; p=0.001). Conclusions: Low-dose BCG had more unfavorable outcomes than did standard-dose BCG in terms of recurrence. Tumor progression, cancer-specific survival, and overall survival were similar between the doses. Low-dose BCG improved adverse effects and withdrawal. In the setting of BCG shortage, low-dose BCG may have strong potential as an alternative.
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spelling doaj.art-9152b9ee23bb4d2fa261967ae79f95d62022-12-21T21:48:01ZengKorean Urological AssociationInvestigative and Clinical Urology2466-04932466-054X2022-03-0163214015010.4111/icu.20210340Low-dose versus standard-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trialsSe Young Choi 0https://orcid.org/0000-0002-4615-0966Moon Soo Ha1https://orcid.org/0000-0001-9735-4347Jung Hoon Kim2https://orcid.org/0000-0002-0947-876XByung Hoon Chi 3https://orcid.org/0000-0002-4184-7780Jin Wook Kim4https://orcid.org/0000-0003-4157-9365In Ho Chang5https://orcid.org/0000-0003-0240-1310Tae-Hyoung Kim6https://orcid.org/0000-0002-0257-3449Soon Chul Myung7https://orcid.org/0000-0002-6727-5450Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Hyundae General Hospital, Chung-Ang University College of Medicine, Namyangju, Korea.Department of Urology, Hanil General Hospital, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.Purpose: Intravesical BCG (bacille Calmette–Guérin) instillation in patients with non-muscle-invasive bladder cancer decreases the risk for tumor recurrence and progression. After one BCG product was discontinued, a chronic global BCG shortage occurred. We focused on identifying a reduced dose of BCG that could maintain efficacy and reduce adverse effects. Materials and Methods: We conducted a comprehensive literature search of PubMed, Embase, the Cochrane Library, CINAHL, Web of Science, and Scopus to identify randomized controlled trials through April 2021. The odds ratios (ORs) and 95% confidence intervals (CIs) for the low and standard doses in nine studies were compared. A low dose was defined as a low volume of BCG compared with the standard BCG dose (Armand Frappier, 120 mg; Connaught, 81 mg; Danish 1331, 120 mg; modified Danish 1331, 120 mg; Tokyo 172, 80 mg). Results: The low-dose group experienced aggravated recurrence (OR, 1.45; 95% CI, 1.09–1.94; p=0.01) but similar progression (OR, 1.11; 95% CI, 0.76–1.62; p=0.59), similar cancer-specific survival (OR, 1.02; 95% CI, 0.60–1.75; p=0.93), similar overall survival (OR, 1.09; 95% CI, 0.76–1.56; p=0.65), favorable adverse effects (OR, 0.41; 95% CI, 0.28–0.62; p<0.0001), and favorable withdrawal (OR, 0.42; 95% CI, 0.25–0.71; p=0.001). Conclusions: Low-dose BCG had more unfavorable outcomes than did standard-dose BCG in terms of recurrence. Tumor progression, cancer-specific survival, and overall survival were similar between the doses. Low-dose BCG improved adverse effects and withdrawal. In the setting of BCG shortage, low-dose BCG may have strong potential as an alternative.https://www.icurology.org/pdf/10.4111/icu.20210340administrationintravesicaladverse effectsrecurrenceurinary bladder neoplasms
spellingShingle Se Young Choi
Moon Soo Ha
Jung Hoon Kim
Byung Hoon Chi
Jin Wook Kim
In Ho Chang
Tae-Hyoung Kim
Soon Chul Myung
Low-dose versus standard-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials
Investigative and Clinical Urology
administration
intravesical
adverse effects
recurrence
urinary bladder neoplasms
title Low-dose versus standard-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials
title_full Low-dose versus standard-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials
title_fullStr Low-dose versus standard-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials
title_full_unstemmed Low-dose versus standard-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials
title_short Low-dose versus standard-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials
title_sort low dose versus standard dose bacille calmette guerin for non muscle invasive bladder cancer systematic review and meta analysis of randomized controlled trials
topic administration
intravesical
adverse effects
recurrence
urinary bladder neoplasms
url https://www.icurology.org/pdf/10.4111/icu.20210340
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