Clinicopathologic and Genomic Characterization of PD-L1 Positive Urothelial Carcinomas

Abstract

Introduction. Pembrolizumab was approved with an accompanying companion diagnostic (CDx) assay (PD-L1 DAKO 22C3) for urothelial carcinoma (UC). In this study, we further characterize the clinicopathologic and genomic features of UC that are PD-L1 positive. Materials and Methods. The cohort of this study consisted of a total of 528 consecutive UC patients with PD-L1 IHC and comprehensive genomic profiling (CGP). All PD-L1 IHC testing was performed using the DAKO 22C3 CDx assay for UC. PD-L1 positivity was determined at a combined positive score (CPS) ≥ 10. Results. 44.5% of 528 consecutive UC patients were PD-L1 positive. A lower PD-L1 positivity rate was detected in primary (42.3%, 148/350) vs metastatic sites (48.9%, 87/178). PD-L1 positivity was dependent on the location of the metastatic sites with PD-L1 positivity rate. CGP revealed PD

PD‐L1 expression and FGFR‐mutations among Danish patients diagnosed with metastatic urothelial carcinoma: A retrospective and descriptive study

“…We found that 29% of primary tumors had a PD‐L1 CPS score of ≥10 ( i.e., positive PD‐L1 expression). This finding is in line with other studies based on the 22C3 antibody, in which 20–40% of UC tumors have a reported PD‐L1 CPS of ≥10 [14,15]. We found no difference in primary tumor PD‐L1 expression according to gender, and in line with one recent study nor according to stage or histological subtype [16].…”

How many Italian cancer patients are eligible for, and may respond to, Italian Medicines Agency-approved immune checkpoint inhibitors?

“…When available we counted on Italian cancer registries, like many others, do not extensively collect information on predictive bio-markers as PD-1/PD-L1, EGFR, ALK, or dMMr/MSI-H. Therefore, we had to use data from the literature [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] (see Online Supplementary Materials) taking a chance of possible individual, tumor and technical variabilities. 41 ICI are usually authorized for advanced or metastatic cancers, therefore we used, according to US and China authors, [12][13][14] the number of cancer deaths provided by the Italian Institute of Statistics as a proxy of incident metastatic cases.…”

“…Italian cancer registries, like many others, do not extensively collect information on predictive bio-markers as PD-1/PD-L1, EGFR, ALK, or dMMr/MSI-H. Therefore, we had to use data from the literature 22 - 38 (see Online Supplementary Materials ) taking a chance of possible individual, tumor and technical variabilities. 41 …”

“…Therefore, we applied the official observed number of citizens who died due to distinct cancers in Italy in the last year available (2020), 18 when available (ISTAT), or on assumption based on Airtum 19,20 or other population-based data. 21 Concerning specific indications, we did not perform a formal revision of the literature for each combination cancer-marker, but searched in PubMed for the terms: type of cancer + metasta*+ type of marker and preferred information coming from Italy, 19,22 when available, rather than foreign countries, 16,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and from population-based 19,22,33,34,38 rather than clinical datasets, 16,[23][24][25][26][27][28][29][30][31][32][35][36][37][38] as well. Further details can be found in the Online Supplementary Materials.…”

“…Concerning specific indications, we did not perform a formal revision of the literature for each combination cancer-marker, but searched in PubMed for the terms: type of cancer + metasta*+ type of marker and preferred information coming from Italy, 19 , 22 when available, rather than foreign countries, 16 , 23 - 37 and from population-based 19 , 22 , 33 , 34 , 38 rather than clinical datasets, 16 , 23 - 32 , 35 - 38 as well. Further details can be found in the Online Supplementary Materials .…”