Oncology - Bladder, Renal, Test
Mid-Atlantic Section 76th Annual Meeting
Introduction & Objective :
Study of the tumor microenvironment in various cancers including urothelial cell carcinoma (UCC) of the bladder has identified programmed death ligand 1 (PD-L1) as a potential target for immunotherapy. Uninhibited, malignant cells expressing PD-L1 complex with programmed death protein 1 (PD-1) and inhibit native T-cell responses to the tumor. Five agents have been approved for bladder cancer which bind to PD-L1 expressed by tumor cells and impede the formation of this complex. Several studies have attempted to validate PD-L1 staining of bladder tumors as a biomarker predictive of response to these agents, but with variable results. It is the goal of this study to evaluate PD-L1 staining fidelity between the primary tumor and lymph node metastases from cystectomy specimens and to evaluate whether neoadjuvant chemotherapy affects this relationship.
In this multicenter trial, two prospectively maintained bladder cancer databases were queried to identify 67 subjects who underwent radical cystectomy between 2008 and 2015 and were found to have residual bladder cancer as well as positive lymph nodes. These cases were retrospectively reviewed, and original pathologic specimens were stained for PD-L1. Primary histology and PD-L1 staining was re-reviewed by a genitourinary pathologist. Specimens were considered “positive” if tumor cells exhibited >1% PD-L1 staining and were also evaluated by H-score. Systematic analysis was used to assess how various clinical variables, including NAC, affected odds of PD-L1 fidelity between primary and metastatic tumors.
Overall PD-L1 staining status was preserved in 79.1% of cases. The interclass correlation coefficient (ICC) between the average bladder and lymph node H-scores was 0.85 (95% CI 0.75 – 0.91). NAC did not significantly impact odds of PD-L1 fidelity (OR 1.974, 95% CI 0.673 - 5.784). Among clinical variables analyzed, male sex was associated with significantly decreased odds of PD-L1 fidelity (OR 0.243, 95% CI 0.079 - 0.744). Bladder and lymph node H-score were also significantly associated with PD-L1 fidelity.
PD-L1 fidelity between primary bladder and metastatic lymph node tumors was observed in >75% of cases in this study. Standard NAC did not impact PD-L1 concordance of tumor cells in this cohort. Further observation of PD-L1 status of both tumor and infiltrating immune cells in metastatic bladder cancer, particularly in the setting of checkpoint inhibitor therapy, will help further elucidate changes in the tumor microenvironment at the time of metastasis and guide therapeutics.