TY - JOUR
T1 - PD-L1 expression in high-risk non-muscle invasive bladder cancer is not a biomarker of response to BCG
AU - de Jong, Florus C.
AU - Kvikstad, Vebjørn
AU - Hoedemaeker, Robert F.
AU - van der Made, Angelique C.J.
AU - van der Bosch, Thierry P.
AU - van Casteren, Niels J.
AU - van Kessel, Kim E.M.
AU - Zwarthoff, Ellen C.
AU - Boormans, Joost L.
AU - Zuiverloon, Tahlita C.M.
N1 - © The Author(s) 2025.
PY - 2025/1/3
Y1 - 2025/1/3
N2 - PurposeUp to 50% of high-risk non-muscle invasive bladder cancer (HR-NMIBC) patients fail Bacillus Calmette-Guérin (BCG) treatment, resulting in a high risk of progression and poor clinical outcomes. Biomarkers that predict outcomes after BCG are lacking. The antitumor effects of BCG are driven by a cytotoxic T cell response, which may be controlled by immune checkpoint proteins like Programmed Death Ligand 1 (PD-L1). Here, we hypothesized that PD-L1 protein expression could serve as a biomarker for BCG-failure.MethodsHR-NMIBC patients who received ≥ 5 BCG instillations were included. Tissue microarrays were constructed from BCG-naïve tumors and recurrences and stained with the PD-L1 (SP142) antibody. PD-L1 status was defined as ≥ 5% tumor-infiltrating immune cells with membrane staining in the tumor area. Clinicopathological associations with PD-L1 positive tumors were investigated, and time-to-event analyses were performed comparing PD-L1 positive vs. negative tumors.Results432 BCG-naïve tumors and 160 recurrences were included, and 91% of patients received adequate BCG. In BCG-naïve tumors, PD-L1 was expressed in 7% of patients and PD-L1 expression was associated with stage T1 versus Ta disease (p = 0.015). PD-L1 expression was not associated with treatment failure after adequate BCG (p = 0.782) nor with progression-free survival (p = 0.732). Testing cut-offs of ≥ 1% and ≥ 10% PD-L1 positivity did not alter results. High PD-L1 expression was more frequent in tumor recurrences (14%) as compared to BCG-naïve tumors (p = 0.012).ConclusionPD-L1 expression in HR-NMIBC is not a biomarker of response to BCG. However, PD-L1 is higher in a subset of tumors that failed BCG treatment. More research is needed to determine the role of PD-L1 in tumors where BCG treatment failed.
AB - PurposeUp to 50% of high-risk non-muscle invasive bladder cancer (HR-NMIBC) patients fail Bacillus Calmette-Guérin (BCG) treatment, resulting in a high risk of progression and poor clinical outcomes. Biomarkers that predict outcomes after BCG are lacking. The antitumor effects of BCG are driven by a cytotoxic T cell response, which may be controlled by immune checkpoint proteins like Programmed Death Ligand 1 (PD-L1). Here, we hypothesized that PD-L1 protein expression could serve as a biomarker for BCG-failure.MethodsHR-NMIBC patients who received ≥ 5 BCG instillations were included. Tissue microarrays were constructed from BCG-naïve tumors and recurrences and stained with the PD-L1 (SP142) antibody. PD-L1 status was defined as ≥ 5% tumor-infiltrating immune cells with membrane staining in the tumor area. Clinicopathological associations with PD-L1 positive tumors were investigated, and time-to-event analyses were performed comparing PD-L1 positive vs. negative tumors.Results432 BCG-naïve tumors and 160 recurrences were included, and 91% of patients received adequate BCG. In BCG-naïve tumors, PD-L1 was expressed in 7% of patients and PD-L1 expression was associated with stage T1 versus Ta disease (p = 0.015). PD-L1 expression was not associated with treatment failure after adequate BCG (p = 0.782) nor with progression-free survival (p = 0.732). Testing cut-offs of ≥ 1% and ≥ 10% PD-L1 positivity did not alter results. High PD-L1 expression was more frequent in tumor recurrences (14%) as compared to BCG-naïve tumors (p = 0.012).ConclusionPD-L1 expression in HR-NMIBC is not a biomarker of response to BCG. However, PD-L1 is higher in a subset of tumors that failed BCG treatment. More research is needed to determine the role of PD-L1 in tumors where BCG treatment failed.
UR - http://www.scopus.com/inward/record.url?scp=85213992408&partnerID=8YFLogxK
U2 - 10.1007/s00345-024-05392-5
DO - 10.1007/s00345-024-05392-5
M3 - Article
C2 - 39752014
AN - SCOPUS:85213992408
SN - 0724-4983
VL - 43
JO - World Journal of Urology
JF - World Journal of Urology
IS - 1
M1 - 57
ER -
