Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder

Owyong, Michael; Lotan, Yair; Kapur, Payal; Panwar, Vandana; McKenzie, Tiffani; Lee, Thomas K.; Zi, Xiaolin; Martin, Jeremy W.; Mosbah, Ahmed; Abol‐Enein, Hassan; Ghoneim, Mohamed A.; Youssef, Ramy

doi:10.1016/j.urolonc.2019.02.017

Cited by 14 publications

(23 citation statements)

References 34 publications

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“…In concordance with the current FDA/EMA guidelines of urothelial cancers calling for PD-L1 positivity to protect from side effects [8,9,26], we revealed frequent PD-L1 expression in squamous bladder tumours up to 62% for immune and up to 52% for tumour cells. These findings, based on four different antibodies (DAKO 28-8, DAKO 22C3, Ventana SP263 and Ventana SP142), confirmed the data of the recent publications [17][18][19] and are comparable with studies of urothelial cancer [10]. So far, ICI treatment is an integral part of the therapy of squamous cancers in other organs like the lung and head and neck: The Checkmate-017 study revealed an improved overall survival (OS) and a favourable safety profile for nivolumab compared to docetaxel in patients with pre-treated squamous NSCLC [27].…”

Section: Discussionsupporting

confidence: 90%

“…pembrolizumab and atezolizumab, have been approved by the FDA and EMA for first-line therapy of platinum-ineligible patients with PD-L1 expression as specified by scoring algorithms [8,9]. Accumulating studies also indicate strong PD-L1 expression in squamous tumors of the urinary bladder [17][18][19], but underlying retrospective cohorts are less suitable to assess the additive value of ICI therapies in SCC disease management: The patient cohort analyzed by Owyong and colleagues comprised mainly Schistosomiasis-associated SCC [17], while the publications by both Reis et al and Udager et al lack sufficient SCC sample numbers [18,19]. Moreover, all studies were characterized by the absence of a clinical setting.…”

Section: Discussionmentioning

confidence: 99%

“…in the Middle East), and non-Schistosomiasis associated SCC [16]. Recently PD-L1 expression was studied in Schistosomiasis-related SCC of the bladder highlighting an association between negative PD-L1 expression and clinico-pathological parameters like tumour stage and unfavourable patients' outcome [17]. In 2018 Udager and colleagues analysed PD-L1 protein expression in 17 pure SCC samples of the urinary bladder demonstrating frequent PD-L1 positivity (65%) [18].…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic implications of PD-L1 expression in bladder cancer with squamous differentiation

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Therapeutic implications of PD-L1 expression in bladder cancer with squamous differentiation

et al. 2020

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“…Thirty-seven studies were screened by full-text examination, and 26 studies were excluded for following reasons: 20 studies did not provide sufficient for analysis, 2 studies recruited overlapped patients, 2 studies were reviews, 1 study did not focus on PD-L1, and 1 study did not use IHC method for PD-L1 detection. Ultimately, 11 studies (Nakanishi et al, 2007; Boorjian et al, 2008; Wang et al, 2009; Xylinas et al, 2014; Bellmunt et al, 2015; Wu et al, 2016; Noro et al, 2017; Li et al, 2018b; Pichler et al, 2018; Owyong et al, 2019; Wang et al, 2019) were included in this meta-analysis. The flow diagram is shown in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

“…PD-L1 expression has shown prognostic value in various tumors including pancreatic cancer (Gao et al, 2018), colorectal cancer (Shen et al, 2019), and non-small cell lung cancer (Ma et al, 2018). Recently, many studies (Nakanishi et al, 2007; Boorjian et al, 2008; Wang et al, 2009; Xylinas et al, 2014; Bellmunt et al, 2015; Wu et al, 2016; Noro et al, 2017; Li et al, 2018b; Pichler et al, 2018; Owyong et al, 2019; Wang et al, 2019) also investigated the prognostic significance of PD-L1 expression in bladder cancer, but the results remain controversial. Therefore, we collected relevant data and performed a meta-analysis to quantify the prognostic role of PD-L1 and analyze the relationship of PD-L1 and clinicopathological parameters in bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Clinicopathological Significance of PD-L1 in Patients With Bladder Cancer: A Meta-Analysis

Zhu

Sun²,

Ling

et al. 2019

Front. Pharmacol.

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Background: The prognostic role of programmed cell death-ligand 1 (PD-L1) in bladder cancer has been investigated in previous studies, but the results remain inconclusive. Therefore, we carried out a meta-analysis to evaluate the prognostic significance of PD-L1 in patients with bladder cancer. Methods: The electronic databases PubMed, Embase, Web of Science, and Cochrane Library were searched. The association between PD-L1 expression and survival outcomes and clinicopathological factors was analyzed by hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 11 studies containing 1,697 patients were included in the meta-analysis. High PD-L1 expression was associated with poor overall survival (OS) (HR = 1.83, 95% CI = 1.24–2.71, p = 0.002). There was nonsignificant association between PD-L1 and recurrence-free survival (RFS) (HR = 1.43, 95% CI = 0.89–2.29, p = 0.134), cancer-specific survival (CSS) (HR = 1.51, 95% CI = 0.80–2.87, p = 0.203), or disease-free survival (DFS) (HR = 1.53, 95% CI = 0.88–2.65, p = 0.13). Furthermore, high PD-L1 was significantly correlated with higher tumor stage (OR = 3.9, 95% CI = 2.71–5.61, p < 0.001) and distant metastasis (OR = 2.5, 95% CI = 1.22–5.1, p = 0.012), while PD-L1 overexpression was not correlated with sex, tumor grade, lymph node status, and multifocality. Conclusions: The meta-analysis suggested that PD-L1 overexpression could predict worse survival outcomes in bladder cancer. High PD-L1 expression may act as a potential prognostic marker for patients with bladder cancer.

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Transcriptome profiling research in urothelial cell carcinoma

et al. 2023

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Urothelial cell carcinoma (UCC) is the ninth most common cancer that accounts for 4.7% of all new cancer cases globally. UCC development and progression are due to complex and stochastic genetic programs. To study the cascades of molecular events underlying the poor prognosis that may lead to limited treatment options for advanced disease and resistance to conventional therapies in UCC, transcriptomics technology (RNA‐Seq), a method of analyzing the RNA content of a sample using modern high‐throughput sequencing platforms has been employed. Here, we review the principles of RNA‐Seq technology and summarize recent studies on human bladder cancer that employed this technique to unravel the pathogenesis of the disease, identify biomarkers, discover pathways and classify the disease state. We list the commonly used computational platforms and software that are publicly available for RNA‐Seq analysis. Moreover, we discussed the future perspectives for RNA‐Seq studies on bladder cancer and recommended the application of a new technology called single‐cell sequencing to further understand the disease.

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Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder

Cited by 14 publications

References 34 publications

Therapeutic implications of PD-L1 expression in bladder cancer with squamous differentiation

Therapeutic implications of PD-L1 expression in bladder cancer with squamous differentiation

Prognostic and Clinicopathological Significance of PD-L1 in Patients With Bladder Cancer: A Meta-Analysis

Transcriptome profiling research in urothelial cell carcinoma

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