Compared Efficacy of Adjuvant Intravesical BCG-TICE vs. BCG-RIVM for High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC): A Propensity Score Matched Analysis.

Andrea Minervini ,Stefano Salciccia,Gian Maria Busetto,M Chirico ,Francesco Soria,Francesco Cinelli,Benjamin I Chung,Luigi Cormio,Martina Maggi,David D’Andrea,Vito Mancini,Savio Domenico Pandolfo,Ugo Giovanni Falagario,Carlo Maria Scornajenghi,Nicola D’Altilia,Null Author_Id ,Laura S Mertens,Ettore De Berardinis,Mario De Angelis,Alessandro Sciarra,Vincenzo Asero,Matteo Ferro,Benjamin Pradère ,Tomasz Szydełko,Simone Albisinni,Giovanni Cacciamani ,Ekaterina Laukhtina,Wojciech Krajewski,Andrea Gallioli,Giuseppe Carrieri,Marco Moschini,Susanna Cattarino,Riccardo Autorino,Carlo Bettocchi,Francesco Del Giudice,Rocco Simone Flammia

doi:10.3390/cancers14040887

Abstract

Simple SummaryIntravesical immunotherapy with bacillus Calmette–Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer. Different BCG strains are currently available and the superiority of any BCG strain over another could not be demonstrated yet. We compared the efficacy of two BCG strains: RIVM and TICE, respectively. In this propensity-score matched cohort study, we showed no particular survival benefit of TICE vs RIVM in the case of high-risk disease. Nevertheless, stratifying our data for re-staging procedures and for those who received BCG maintenance, we identified BCG TICE to improve RFS independently. Herein, we corroborated the importance of performing a routine secondary resection followed by an adequate maintenance course of BCG. Future larger prospective randomized head-to-head trials are needed to further elucidate this important topic, especially in this era of BCG shortage.Background: Intravesical immunotherapy with bacillus Calmette–Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet. Methods: Patients with NMIBCs underwent adjuvant induction ± maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naïve patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan–Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed. Results: 852 Ta-T1 NMIBCs (n = 719, 84.4% on TICE; n = 133, 15.6% on RIVM) with a median of 53 (24–77) months of follow-up were reviewed. After PSM, no differences at 5-years RFS, PFS, and CSS at both Kaplan–Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, p = 0.008; HR: 0.45 95% CI 0.25–0.81). Conclusion: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively.

Highlights

Adjuvant intravesical Bacillus of Calmette–Guérin (BCG) for the treatment of nonmuscle invasive bladder cancer (NMIBC) was successfully introduced in 1976 by Morales et al [1]
Given the existence of substantial heterogeneity among the two cohorts in terms of age, gender, and other non-muscle invasive bladder cancer (NMIBC) prognostic risk factors, a propensity score matching (PSM) was applied across the whole study population
After adjustment for the risk of recurrence, undergoing re-TUR was found as an independent predictor for prolonged recurrence-free survival (RFS) (HR: 0.71; 95% confidence intervals (CI): 0.57–0.88; p = 0.002) with no differences detected when after the procedure was administered one of the two strain

Summary

Introduction

Adjuvant intravesical Bacillus of Calmette–Guérin (BCG) for the treatment of nonmuscle invasive bladder cancer (NMIBC) was successfully introduced in 1976 by Morales et al [1] It was subsequently established as the standard of care following trans-urethral resection of bladder tumor (TURBT) for intermediate/high-risk cases according to both American and European Urology Guidelines (National Comprehensive Cancer Network [NCCN], EAU) [2,3,4]. The recently released NIMBUS trial [8] demonstrated that a reduced-frequency BCG schedule, or the use of dose-reduced instillations, are inferior to the standard schedule regarding the time to first recurrence These considerations, together with the above-mentioned studies, are relevant in light of recent supply chain issues in acquiring BCG. No significant differences were detected for PFS and CSS, respectively

Methods

Results

Conclusion