PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy
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Renate Pichler1,*, Isabel Heidegger1,*, Josef Fritz2, Melanie Danzl3, Susanne Sprung3, Bettina Zelger3, Andrea Brunner3 and Andreas Pircher4
1Department of Urology, Medical University Innsbruck, Innsbruck, Austria
2Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Innsbruck, Austria
3Department of Pathology, Division of General Pathology, Medical University Innsbruck, Innsbruck, Austria
4Department of Internal Medicine V, Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria
*These authors have contributed equally to this work
Renate Pichler, email: [email protected]
Keywords: bladder cancer, cystectomy, survival, PD-L1, immunotherapy
Received: May 10, 2017 Accepted: June 30, 2017 Published: August 03, 2017
Platinum-based chemotherapy is the standard of care in metastatic bladder cancer. With the approval of various checkpoint inhibitors, immunotherapy has revolutionized the traditional treatment modalities. The aim of the study was to evaluate whether PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) can be used as biomarker to predict recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS) in bladder cancer patients after radical cystectomy (RC) developing disease recurrence followed by first-line chemotherapy. PD-L1 was measured on formalin-fixed, paraffin-embedded tissue sections of RC specimens in all patients (n=61) and in 27 matched metastatic biopsy samples by immunohistochemistry. PD-L1 expression on TCs was defined by the percentage of PD-L1 positive tumor cells (< 1%= IC0, ≥1% but <5%=IC1, ≥5 %=IC2/3), and was considered negative or positive for ICs. On 27 paired samples, IC1/2/3 score on TCs was homogeneous distributed with 59.3% in primary tumors and metastases, but with a high discordance rate of 44.4% of PD-L1 positivity on ICs. High PD-L1 expression (IC2/3) on TCs was more frequently seen in histologic subtypes of urothelial cancer compared to pure urothelial cancers (46.2% vs. 20.8%; p=0.002). PD-L1 expression on TCs in primary tumors (IC2/3 vs. IC0, median: 3.2 vs. 13.8 months, p=0.019) and metastatic sites (IC2/3 vs. IC0, median: 6.1 vs. 21.8 months, p=0.014) was associated with poor chemo-response, represented by significant shortened DSS. These results suggest that PD-L1 may be a potential target being involved in chemo-resistance mechanisms and poses potential for therapy stratification in the future.
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