PD-L1 expression in bladder cancer: Which scoring algorithm in what tissue?

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• First-line immunotherapy for cisplatin-ineligible bladder cancer patients depends on programmed death ligand 1 (PD-L1) expression assays (combined positive score [CPS] or immune cell [IC] score).
• Accurate PD-L1 assessment is crucial for determining patient eligibility for immune-checkpoint inhibitor (ICI) therapy.

Purpose of the Study:

• To compare PD-L1 diagnostic scores and positivity in primary bladder cancer (BC) versus matched metastatic lymph node tissue.
• To evaluate the correlation between PD-L1 expression in primary and metastatic sites.
• To compare the performance of CPS and IC scoring algorithms for PD-L1 assessment.

Main Methods:

• Immunohistochemistry (IHC) was used to assess PD-L1 expression in primary BC and lymph node metastases from 108 patients.
• Ventana SP263, SP142, and Dako 22C3 antibodies were employed for PD-L1 staining.
• Statistical analyses included Pearson's chi-square test, McNemar test, and Spearman correlation to compare PD-L1 scores and assess correlations.

Main Results:

• PD-L1 expression did not correlate with clinicopathological parameters.
• Primary BC tissue showed significantly higher PD-L1 positivity than matched lymph node metastases for both CPS (43.5% vs. 35.6%) and IC scores (28.7% vs. 21.2%).
• Both CPS and IC scores demonstrated strong correlations between primary and metastatic tissues (r=0.775 and r=0.711, respectively). The CPS identified more PD-L1-positive cases than the IC score in both primary and metastatic tissues.

Conclusions:

• Bladder tumor tissue yields higher PD-L1 positivity compared to lymph node metastases, particularly when using the CPS assay.
• These findings suggest that utilizing both PD-L1 assays (CPS and IC) may maximize the eligibility of cisplatin-ineligible bladder cancer patients for first-line ICI therapy.