Delaying BCG immunotherapy onset after transurethral resection of non-muscle-invasive bladder cancer is associated with

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ORIGINAL ARTICLE

Delaying BCG immunotherapy onset after transurethral resection of non‑muscle‑invasive bladder cancer is associated with adverse survival outcomes Wojciech Krajewski1   · Marco Moschini2 · Joanna Chorbińska1 · Łukasz Nowak1 · Sławomir Poletajew3 · Andrzej Tukiendorf4 · Luca Afferi2 · Jeremy Yuen‑Chun Teoh5 · Tim Muilwijk6 · Steven Joniau6 · Alessandro Tafuri7 · Alessandro Antonelli7 · Francesco Cianflone7 · Andrea Mari8 · Ettore Di Trapani9 · Kees Hendricksen10 · Mario Alvarez‑Maestro11 · Andrea Rodríguez‑Serrano11 · Giuseppe Simone12 · Stefania Zamboni13,14 · Claudio Simeone13,14 · Maria Cristina Marconi13,14 · Riccardo Mastroianni12 · Guillaume Ploussard15 · Ekaterina Laukhtina16,17 · Karl Tully18 · Anna Kołodziej1 · Joanna Krajewska19 · Radosław Piszczek20 · Evanguelos Xylinas21 · Romuald Zdrojowy1 · European Association of Urology—Young Academic Urologists (EAUYAU): Urothelial carcinoma working group Received: 20 August 2020 / Accepted: 4 November 2020 © The Author(s) 2020

Abstract Purpose  This study was carried out to assess whether a prolonged time between primary transurethral resection of nonmuscle-invasive bladder cancer (TURB) and implementation of bacillus Calmette–Guerin (BCG) immunotherapy (time to BCG; TTBCG) is associated with adverse oncological survival in patients with T1 high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). Materials and methods  Data on 429 patients from 13 tertiary care centers with primary T1HG NMIBC treated with reTURB and maintenance BCG between 2001 and 2019 were retrospectively reviewed. Change-point regression was applied following Muggeo’s approach. The population was divided into subgroups according to TTBCG, whereas the recurrence-free survival (RFS) and progression-free survival (PFS) were estimated with log-rank tests. Additionally, Cox regression analyses were performed. Due to differences in baseline patient characteristics, propensity-score-matched analysis (PSM) and inverseprobability weighting (IPW) were implemented. Results  The median TTBCG was 95 days (interquartile range (IQR): 71–127). The change-point regression analysis revealed a gradually increasing risk of recurrence with growing TTBCG. The risk of tumor progression gradually increased until a TTBCG of approximately 18 weeks. When the study population was divided into two subgroups (time intervals: ≤ 101 and > 101 days), statistically significant differences were found for both RFS (p = 0.029) and PFS (p = 0.005). Furthermore, in patients with a viable tumor at reTURB, there were no differences in RFS and PFS. After both PSM and IPW, statistically significant differences were found for both RFS and PFS, with worse results for longer TTBCG. Conclusion  This study shows that delaying BCG immunotherapy after TURB of T1HG NMIBC is associated with an increased risk of tumor recurrence and progression. Keywords  Bladder cancer · BCG · Time · Delay · Survival

The members of the "European Association of Urology - Young Academic Urologists (EAU-YAU): Urothelial carcinoma working group"