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Therapeutic implications of PD-L1 expression in bladder cancer with squamous differentiation
Ronja Morsch1,2, Michael Rose2, Angela Maurer2
1Department of Urology, University Hospital RWTH Aachen University, Aachen, Germany.
Background:
Immune checkpoint inhibitors (ICI) are an integral part of bladder cancer therapy, however, the relevance of ICI treatment for mixed and pure squamous cell carcinoma of the bladder remains poorly studied. Therefore, we analysed the expression of programmed death-ligand 1 (PD-L1) in urothelial carcinomas with squamous differentiation (UC/SCC) and pure squamous cell carcinoma (SCC) of the bladder and studied a UC/SCC patient with ICI therapy.
Methods:
Tissue microarrays of 45 UC/SCC and 63 SCC samples were immunohistochemically stained with four anti-PD-L1 antibodies (28-8, 22C3, SP142 and SP263). PD-L1 expression was determined for tumour cells (TP-Score), immune cells (IC-Score) and combined (CPS, combined positive score). In addition, we present clinical and histological data of an UC/SCC patient with nivolumab therapy.
Results:
Overall, positive PD-L1 staining ranged between 4.8 and 61.9% for IC and 0 and 51.2% for TC depending on the used antibody. There were no significant differences between UC/SCC and SCC. According to current FDA guidelines for example for first line therapy of urothelial cancer with pembrolizumab (CPS ≥ 10), a subset of SCC patients up to 20% would be eligible. Finally, our UC/SCC index patient revealed excellent therapy response regarding his lung metastasis.
Conclusions:
Our data reveal a PD-L1 expression in squamous differentiated carcinomas comparable with current data shown for urothelial tumours. In accordance with the encouraging clinical data of the index patient we suggest ICI treatment also for mixed and pure SCC of the urinary bladder.
Insights
Immune checkpoint inhibitors (ICI) show PD-L1 expression in squamous cell bladder cancer, similar to urothelial tumors. This suggests ICI therapy may benefit patients with mixed or pure squamous cell carcinoma of the bladder.
Area of Science:
- Oncology
- Immunotherapy
- Urothelial Carcinomas
Background:
- Immune checkpoint inhibitors (ICI) are crucial for bladder cancer treatment.
- The efficacy of ICI in mixed and pure squamous cell carcinoma (SCC) of the bladder is understudied.
- Programmed death-ligand 1 (PD-L1) expression is a key biomarker for ICI therapy.
Purpose of the Study:
- To analyze PD-L1 expression in urothelial carcinomas with squamous differentiation (UC/SCC) and pure SCC of the bladder.
- To evaluate the potential of ICI treatment for these bladder cancer subtypes.
- To present a case study of a UC/SCC patient receiving ICI therapy.
Main Methods:
- Immunohistochemical staining of 45 UC/SCC and 63 SCC bladder tissue samples using four distinct PD-L1 antibodies.
- Quantification of PD-L1 expression on tumor cells (TP-Score) and immune cells (IC-Score), and calculation of the combined positive score (CPS).
- Clinical and histological data review of a UC/SCC patient treated with nivolumab.
Main Results:
- PD-L1 expression varied significantly based on the antibody used, with positive staining ranging from 4.8% to 61.9% for IC and 0% to 51.2% for TC.
- No significant differences in PD-L1 expression were observed between UC/SCC and SCC.
- A notable subset of SCC patients (up to 20%) could be eligible for therapies like pembrolizumab based on FDA guidelines (CPS ≥ 10).
- The index UC/SCC patient demonstrated an excellent response to nivolumab therapy for lung metastasis.
Conclusions:
- PD-L1 expression in squamous differentiated bladder carcinomas is comparable to urothelial tumors.
- The study supports the consideration of ICI treatment for mixed and pure squamous cell carcinoma of the bladder.
- Encouraging clinical response in the index patient warrants further investigation into ICI efficacy for these subtypes.
