Urologic oncology · 2025
Impact of baseline PD-L1 status in BCG naive nonmuscle invasive bladder cancer on outcomes and changes after BCG exposure.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Gerald Thomas, Woldu Solomon L, Halstuch Daniel, Ber Yaara, Lifshitz Karin, Cook Grayden, Francis Franto, Margel David, Jia Liwei, Lotan Yair
Аннотация
INTRODUCTION: While BCG remains standard of care adjuvant treatment for high-risk nonmuscle invasive bladder cancer (NMIBC), predicting response to BCG therapy is difficult. PD-L1 expression in the tumor microenvironment is a biomarker which may impact the efficacy of immunotherapy. The purpose of this study is to determine the predicative ability of PD-L1 for BCG-unresponsiveness in BCG-naïve high-risk NMIBC.
MATERIALS AND METHODS: We performed a retrospective review of high-risk NMIBC patients treated with BCG in the United States (108) and Israel (124) from 2008 to 2014. PD-L1 status of BCG-naïve specimens determined with Dako 22c3 assay (CPS > 0) at initial transurethral resection was correlated with outcomes, primarily BCG-unresponsiveness. The impact of BCG exposure on PD-L1 expression was analyzed in patients who had sequential tumor sampling.
RESULTS: Of 232 patients, 48 (21.6%) were BCG-unresponsive. PD-L1 expression was positive in 20 (9.2%) and in 5 (5.4%), 15 (14.3%), and 0 of Ta, T1, and CIS, respectively. In the US cohort, BCG-unresponsiveness occurred in 2 (14.3%) of PD-L1 positive and 36 (42.9%) of PD-L1 negative patients (P = 0.042). Tumors with baseline PD-L1 positivity were associated with a lower rate of BCG-unresponsiveness (OR 0.14; 95%CI 0.03-0.76). The predictive value of PD-L1 status in determining BCG-unresponsiveness was poor (AUC 0.57, 95%CI 0.46-0.69). Changes from PD-L1 negative to positive status after BCG exposure were observed, indicating a possible mechanism of resistance to BCG.
CONCLUSIONS: While PD-L1 status was an imperfect overall biomarker for BCG unresponsiveness, there was an association between initial PD-L1 expression and BCG response. Additionally, there was an upregulation of PD-L1 expression in BCG unresponsive specimens. These findings generate a hypothesis-generating discussion regarding the tumor immune-microenvironment and its response to BCG. Further investigation is necessary to better understand this interaction and its impact on tumor biomarker profiling and patient selection for combination therapy.
MATERIALS AND METHODS: We performed a retrospective review of high-risk NMIBC patients treated with BCG in the United States (108) and Israel (124) from 2008 to 2014. PD-L1 status of BCG-naïve specimens determined with Dako 22c3 assay (CPS > 0) at initial transurethral resection was correlated with outcomes, primarily BCG-unresponsiveness. The impact of BCG exposure on PD-L1 expression was analyzed in patients who had sequential tumor sampling.
RESULTS: Of 232 patients, 48 (21.6%) were BCG-unresponsive. PD-L1 expression was positive in 20 (9.2%) and in 5 (5.4%), 15 (14.3%), and 0 of Ta, T1, and CIS, respectively. In the US cohort, BCG-unresponsiveness occurred in 2 (14.3%) of PD-L1 positive and 36 (42.9%) of PD-L1 negative patients (P = 0.042). Tumors with baseline PD-L1 positivity were associated with a lower rate of BCG-unresponsiveness (OR 0.14; 95%CI 0.03-0.76). The predictive value of PD-L1 status in determining BCG-unresponsiveness was poor (AUC 0.57, 95%CI 0.46-0.69). Changes from PD-L1 negative to positive status after BCG exposure were observed, indicating a possible mechanism of resistance to BCG.
CONCLUSIONS: While PD-L1 status was an imperfect overall biomarker for BCG unresponsiveness, there was an association between initial PD-L1 expression and BCG response. Additionally, there was an upregulation of PD-L1 expression in BCG unresponsive specimens. These findings generate a hypothesis-generating discussion regarding the tumor immune-microenvironment and its response to BCG. Further investigation is necessary to better understand this interaction and its impact on tumor biomarker profiling and patient selection for combination therapy.