Compared Efficacy of Adjuvant Intravesical BCG-TICE vs. BCG-RIVM for High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC): A Propensity Score Matched Analysis
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Francesco Del Giudice
1,2,*
,
Rocco Simone Flammia
1
,
Benjamin I. Chung
2,
Marco Moschini
3,
Benjamin Pradere
4,
Andrea Mari
5
,
Francesco Soria
6,
Simone Albisinni
7,
Wojciech Krajewski
8, 
Tomasz Szydełko
8,
Ekaterina Laukhtina
4,9,
David D’Andrea
4,
Andrea Gallioli
10,
Laura S. Mertens
11, 
Martina Maggi
1
,
Alessandro Sciarra
1,
Stefano Salciccia
1,
Matteo Ferro
12,
Carlo Maria Scornajenghi
1,
Vincenzo Asero
1,
Susanna Cattarino
1,
Mario De Angelis
3,
Giovanni E. Cacciamani
13, 
Riccardo Autorino
14,
Savio Domenico Pandolfo
14,15
,
Ugo Giovanni Falagario
15,
Nicola D’Altilia
16,
Vito Mancini
16
,
Marco Chirico
16,
Francesco Cinelli
16,
Carlo Bettocchi
16, 
Luigi Cormio
16,
Giuseppe Carrieri
16,
Ettore De Berardinis
1,†,
Gian Maria Busetto
16,†
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1
Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, “Sapienza” Rome University, 00185 Rome, Italy
2
Department of Urology, Stanford Medical Center, Stanford, CA 94305, USA
3
Department of Urology, San Raffaele Hospital and Scientific Institute, 20132 Milan, Italy
4
Department of Urology, Medical University of Vienna, 1090 Vienna, Austria
5
Unit of Oncologic Minimally-Invasive Urology and Andrology, Department of Experimental and Clinical Medicine, Careggi Hospital, University of Florence, 50134 Florence, Italy
6
Urology Division, Department of Surgical Sciences, University of Studies of Torino, 10126 Turin, Italy
7
Urology Department, Erasme Hospital, Université Libre de Bruxelles, 1070 Brussels, Belgium
8
Department of Urology and Oncological Urology, Wrocław Medical University, 50-556 Wrocław, Poland
9
Institute for Urology and Reproductive Health, Sechenov University, 19435 Moscow, Russia
10
Unit of Urology, Fundacio Puigvert, 08025 Barcelona, Spain
11
Department of Urology, The Netherlands Cancer Institute, 1066 Amsterdam, The Netherlands
12
Division of Urology, European Institute of Oncology (IEO)-IRCCS, 20141 Milan, Italy
13
USC Institute of Urology, University of Southern California, Los Angeles, CA 90089, USA
14
Division of Urology, Department of Surgery, Virginia Commonwealth University, Richmond, VA 23284, USA
15
Department of Neurosciences, Sciences of Reproduction, and Odontostomatology, Fderico II University, 80131 Naples, Italy
16
Department of Urology and Renal Transplantation, Policlinico Riuniti di Foggia, University of Foggia, 71122 Foggia, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
Members of European Association of Urology (EAU)—Young Academic Urologists (YAU) Urothelial Cancer Working Party are listed in the Acknowledgements.
Cancers 2022, 14(4), 887; https://doi.org/10.3390/cancers14040887
Submission received: 6 January 2022
/
Revised: 1 February 2022
/
Accepted: 6 February 2022
/
Published: 10 February 2022
(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle Invasive Bladder Cancer)
Simple Summary
Intravesical 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.
Abstract
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.
