PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy

In the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacill...

Full description

Bibliographic Details
Main Authors: Moritz Maas, Andreas Hilsendecker, Alexandra Pertoll, Viktoria Stühler, Simon Walz, Steffen Rausch, Arnulf Stenzl, Igor Tsaur, Jörg Hennenlotter, Stefan Aufderklamm
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/16/7/1356
_version_ 1797212810582687744
author Moritz Maas
Andreas Hilsendecker
Alexandra Pertoll
Viktoria Stühler
Simon Walz
Steffen Rausch
Arnulf Stenzl
Igor Tsaur
Jörg Hennenlotter
Stefan Aufderklamm
author_facet Moritz Maas
Andreas Hilsendecker
Alexandra Pertoll
Viktoria Stühler
Simon Walz
Steffen Rausch
Arnulf Stenzl
Igor Tsaur
Jörg Hennenlotter
Stefan Aufderklamm
author_sort Moritz Maas
collection DOAJ
description In the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacillus Calmette–Guérin (BCG) therapy in HR NMIBC patients is scarce. This retrospective study analyzed 126 HR NMIBC tissue samples from 63 patients (38× BCG-treated, 25× BCG-naïve) at two time points to assess PD-L1 expression using the ‘combined positivity score’ (CPS) with the 22C3 DAKO antibody method and correlated it with clinicopathological parameters. A CPS > 10 defined PD-L1 positivity. The impact of initial PD-L1 status and its change over time on time-to-recurrence, progression-free survival, and overall survival (TTR, PFS, OS) was analyzed using Kaplan–Meier and Cox proportional hazard models. BCG treatment significantly increased PD-L1 expression (5.31 vs. 0.22, <i>p</i> = 0.0423), with PD-L1 positive cases rising post-treatment in the BCG group and remaining unchanged in BCG-naïve patients. Multivariate analysis including T-stage, CIS, grading, tumor size, multifocality, age, and sex revealed a significant correlation between PD-L1 status change to positivity and improved TTR (<i>p</i> = 0.03). Our findings demonstrate a potential modulation of the PD-L1 status by an intravesical BCG therapy. However, its prognostic value appears limited.
first_indexed 2024-04-24T10:48:18Z
format Article
id doaj.art-d7bdad54e3ca4cbabf0c7ea531497219
institution Directory Open Access Journal
issn 2072-6694
language English
last_indexed 2024-04-24T10:48:18Z
publishDate 2024-03-01
publisher MDPI AG
record_format Article
series Cancers
spelling doaj.art-d7bdad54e3ca4cbabf0c7ea5314972192024-04-12T13:16:07ZengMDPI AGCancers2072-66942024-03-01167135610.3390/cancers16071356PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) TherapyMoritz Maas0Andreas Hilsendecker1Alexandra Pertoll2Viktoria Stühler3Simon Walz4Steffen Rausch5Arnulf Stenzl6Igor Tsaur7Jörg Hennenlotter8Stefan Aufderklamm9Department of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tübingen, Eberhard Karls University, 72076 Tuebingen, GermanyIn the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacillus Calmette–Guérin (BCG) therapy in HR NMIBC patients is scarce. This retrospective study analyzed 126 HR NMIBC tissue samples from 63 patients (38× BCG-treated, 25× BCG-naïve) at two time points to assess PD-L1 expression using the ‘combined positivity score’ (CPS) with the 22C3 DAKO antibody method and correlated it with clinicopathological parameters. A CPS > 10 defined PD-L1 positivity. The impact of initial PD-L1 status and its change over time on time-to-recurrence, progression-free survival, and overall survival (TTR, PFS, OS) was analyzed using Kaplan–Meier and Cox proportional hazard models. BCG treatment significantly increased PD-L1 expression (5.31 vs. 0.22, <i>p</i> = 0.0423), with PD-L1 positive cases rising post-treatment in the BCG group and remaining unchanged in BCG-naïve patients. Multivariate analysis including T-stage, CIS, grading, tumor size, multifocality, age, and sex revealed a significant correlation between PD-L1 status change to positivity and improved TTR (<i>p</i> = 0.03). Our findings demonstrate a potential modulation of the PD-L1 status by an intravesical BCG therapy. However, its prognostic value appears limited.https://www.mdpi.com/2072-6694/16/7/1356bladder cancernon-muscle-invasive bladder cancerimmunotherapyBCGbiomarker
spellingShingle Moritz Maas
Andreas Hilsendecker
Alexandra Pertoll
Viktoria Stühler
Simon Walz
Steffen Rausch
Arnulf Stenzl
Igor Tsaur
Jörg Hennenlotter
Stefan Aufderklamm
PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy
Cancers
bladder cancer
non-muscle-invasive bladder cancer
immunotherapy
BCG
biomarker
title PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy
title_full PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy
title_fullStr PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy
title_full_unstemmed PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy
title_short PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy
title_sort pd l1 expression in high risk non muscle invasive bladder cancer is influenced by intravesical bacillus calmette guerin bcg therapy
topic bladder cancer
non-muscle-invasive bladder cancer
immunotherapy
BCG
biomarker
url https://www.mdpi.com/2072-6694/16/7/1356
work_keys_str_mv AT moritzmaas pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT andreashilsendecker pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT alexandrapertoll pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT viktoriastuhler pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT simonwalz pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT steffenrausch pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT arnulfstenzl pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT igortsaur pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT jorghennenlotter pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy
AT stefanaufderklamm pdl1expressioninhighrisknonmuscleinvasivebladdercancerisinfluencedbyintravesicalbacilluscalmetteguerinbcgtherapy