Bacillus Calmette-Guérin Strain Differences Have an Impact on Clinical Outcome in Bladder Cancer Immunotherapy

Rentsch, Cyrill A.; Birkhäuser, Frédéric D.; Biot, Claire; Gsponer, Joël; Bisiaux, Aurélie; Wetterauer, Christian; Lagranderie, M.; Marchal, G; Orgeur, Mickael; Bouchier, Christiane; Bachmann, Alexander; Ingersoll, Molly A.; Brosch, Roland; Albert, Matthew L.; Thalmann, George N.

doi:10.1016/j.eururo.2014.02.061

Cited by 174 publications

(155 citation statements)

References 31 publications

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“…The median follow-up after the start of BCG treatment was 33.6 months, and the 2-year recurrence-free survival rate was 56.0% (95% CI, 34.2%-73.1%) (Supplemental Figure 3A). Patients show similar recurrence-free survival as previously described in larger cohorts of patients treated with the same BCG strain (TICE) (6,16). When we segregated patients into groups on the basis of urine frequency of neutrophils (Figure 2A), T cells (Figure 2B), and M-MDSCs ( Figure 2C) (i.e., mean percentage in post-BCG urine samples greater than versus less than the median), we found no significant difference in recurrence-free survival rates, The mean T cell/MDSC ratio in post-BCG urine samples identified 2 groups: patients with higher frequencies of M-MDSCs than of T cells (i.e., log ratio <0) and conversely (i.e., log ratio >0).…”

Section: Characterization Of Immune Cells Present In the Urine Duringsupporting

confidence: 57%

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

Chevalier

Trabanelli

Racle

et al. 2017

Journal of Clinical Investigation

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Section: Characterization Of Immune Cells Present In the Urine Duringsupporting

confidence: 57%

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

Chevalier

Trabanelli

Racle

et al. 2017

Journal of Clinical Investigation

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186

151

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“…Two recent randomized controlled trials (RCTs) have compared different BCG strains. The Tice and Connaught strains have similar side effects (42% vs. 28%, P = 0.09) [25] and no difference in intolerability for the Tokyo and Connaught strains (8.1% vs. 9.8%, P = 0.70) was shown [26]. Andius et al reduced the instillation dwell time to less than 30 min [27].…”

Section: Discussionmentioning

confidence: 99%

BCG immunotherapy for non-muscle invasive bladder cancer: is efficacy related to toxicity?

Udovicich

Nankivell²,

Barberi

et al. 2017

Bladder

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OBJECTIVES:To examine the prevalence of local and systemic adverse effects (AEs) associated with Bacillus Calmette-Guerin (BCG) immunotherapy for non-muscle invasive bladder cancer (NMIBC) and to determine if there was any relationship between adverse effects and efficacy of treatment. PATIENTS AND METHODS:Patients receiving induction intravesical BCG immunotherapy for NMIBC from 1995 to 2013 were identified from a group urology practice. Patients completed an AE scoresheet and an AE was recorded if the patient experienced the symptom at any point in the week following instillation. Patients were dichotomised based on recurrence status (treatment efficacy was defined as non-recurrence) and association with AEs was investigated using univariate Cox regression analysis. RESULTS:One hundred and fifty eight patients were examined with a mean age of 70.2 years (range 41-88) and a male predominance (125, 79%). The most prevalent local AEs were frequency (107, 68%), dysuria (98, 62%) and nocturia (95, 60%). Malaise (54, 34%), myalgia (41, 26%) and fever (32, 20%) were the most common systemic AEs. Recurrence status was available for 82 patients, with 43 (52%) diagnosed with recurrence. There was no significant relationship between overall AEs and recurrence [hazard ratio (HR) 0.97, P = 0.57], or for local (HR 0.99, P = 0.90) and systemic (HR 0.88, P = 0.32) AEs. Only frequency was significantly associated with reduced recurrence (HR = 0.42, P = 0.04). CONCLUSIONS:AEs due to BCG immunotherapy are common in the induction period with nearly 70% of patients in our cohort experiencing individual symptoms. Local AEs are considerably more prevalent than systemic. Frequency was the only AE to be significantly associated with non-recurrence. Overall, AEs due to BCG instillation treatment were not related to efficacy for NMIBC.

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“…9 A recent randomized clinical trial has shown that superior immunogenicity and efficacy of BCG Connaught strain when compared with BCG Tice strain. 21 In addition, anti-tuberculous medications may have reduced the efficacy of the immunotherapy with intravesical BCG especially in the first patient with persistent CIS who had refused cystoprostatectomy. Therefore, in patients with renal granulomas without systemic symptoms, renal granulomas may resolve spontaneously without the need for anti-tuberculous medications.…”

Section: Discussionmentioning

confidence: 99%

BCG-Related Renal Granulomas Managed Conservatively

Al‐Qaoud¹,

Brimo²,

Aprikian³

et al. 2015

CUAJ

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Introduction: The aim of this case series is to present two cases of renal granulomas discovered incidentally post-intravesical Bacillus Calmette-Guerin (BCG) installations and were managed conservatively. Case reports: The first case is a 68-year-old man with bladder and right ureteral orifice carcinoma in situ. After transurethral resection of the right ureteral orifice and bladder tumours, he received 6 + 3 weekly intravesical installations of BCG and then 6 + 3 weekly intravesical installations of BCG with interferon alpha (IFN) in the presence of an indwelling ureteral stent since he had refused cystoprostatectomy. At the 18-month follow-up, his computed tomography scan showed two right renal masses. Biopsy demonstrated non-necrotizing granulomatosis. Serial follow-up with imaging studies showed complete resolution of these masses without antituberculous medications. The second case is a 74-year old man with left renal high-grade papillary urothelial carcinoma. After ureteral meatotomy and insertion of indwelling ureteral stents, he received 6 weekly intravesical installations of BCG followed by 3 weekly installations of BCG and IFN prior to the definitive management with laparoscopic left nephroureterectomy. Final pathology showed pT1 urothelial carcinoma and an incidental finding of BCG-related renal granulamotosis. The patient has been asymptomatic and did not require anti-tuberculous medications. Conclusions: While these two cases demonstrate the ability of intravesical BCG to reach the renal pelvis, patients with a history of intravesical BCG with incidental renal masses may benefit from renal biopsy. These renal granulomas may resolve without antituberculous medications.

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Bacillus Calmette-Guérin Strain Differences Have an Impact on Clinical Outcome in Bladder Cancer Immunotherapy

Cited by 174 publications

References 31 publications

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

BCG immunotherapy for non-muscle invasive bladder cancer: is efficacy related to toxicity?

BCG-Related Renal Granulomas Managed Conservatively

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