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Molecular predictors of response to PD-1/PD-L1 inhibition in urothelial cancer

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Abstract

Introduction

The survival of patients with metastatic urothelial cancer (mUC) is poor. During the last 40 years, chemotherapy was the predominant treatment modality for mUC. The discovery of the immune checkpoint inhibitors (ICI), especially the inhibitors of the programmed cell death 1 and its ligand (PD-1/PD-L1), has revolutionized cancer immunotherapy. The PD-1 and PD-L1 inhibitors provide a new and effective treatment option for patients with UC, particularly for patients with recurrence after platinum-based therapy and those who are ineligible for cisplatin.

Methods

A literature search on PubMed, ClinicalTrials.gov and selected annual congress abstracts was conducted in May 2018, using a combination of keywords, medical subject headings (MeSH) terms and free text incorporating urothelial bladder cancer; immunotherapy; immune checkpoint inhibition, biomarkers, PD1/PD-L1.

Results

Although some patients demonstrate complete and/or durable responses under ICI, the reliable prediction of response to ICI is not possible. In the clinical setting, physicians are not able to predict response to ICI in mUC and to adequately select patients who will benefit. Exploratory analysis of clinical trial data revealed that PD-L1 expression, tumor mutation burden, tumor-infiltrating lymphocytes and gene expression profiles might have some predictive and/or prognostic value in different patient populations.

Conclusion

Validated robust biomarkers are still needed to overcome this hurdle to forecast response of ICI in UC patients.

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Authors and Affiliations

  1. Department of Urology, Eberhard Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany

    Viktoria Stühler, Jan Moritz Maas, Inês Anselmo da Costa, Tilman Todenhöfer, Arnulf Stenzl & Jens Bedke

  2. Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany

    Jonas Bochem

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  2. Jan Moritz Maas
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Project development: JB, VS. Data collection and management: VS, JMM, IAC. Data analysis: VS, JB, TT, JB. Manuscript writing and editing: all authors.

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Correspondence to Jens Bedke.

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Bedke: honoraria/research funding: AstraZeneca, Astellas, BMS, MSD, Pfizer, Roche; Stenzl: honoraria/research funding: BMS, MSD, Pfizer, Roche; Todenhöfer: BMS, MSD, Roche

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Stühler, V., Maas, J.M., Bochem, J. et al. Molecular predictors of response to PD-1/PD-L1 inhibition in urothelial cancer. World J Urol 37, 1773–1784 (2019). https://doi.org/10.1007/s00345-018-2538-6

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