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Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy

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A Letter to the Editor to this article was published on 04 April 2020

Abstract

Purpose

Programmed cell death-1 ligand-1 (PD-L1) expression has been associated with prognostic implications in urologic malignancies. We aimed to investigate prognostic significance of pre- and post-treatment PD-L1 expression in patients treated with BCG for high-grade non-muscle-invasive bladder cancer (NMIBC).

Methods

We reviewed a total of 141 high-grade NMIBC cases treated with transurethral resection +  ≥ 6 BCG instillations between 2004 and 2017. PD-L1 immunohistochemistry (IHC) scoring was done on 0–3 scale, and cut-off for positive and high-level PD-L1 expression was set to ≥ 1% and ≥ 5% staining of tumor-infiltrating immune cells (IC), respectively. Clinicopathologic characteristics and oncologic outcomes [recurrence-free (RFS) and progression-free survival (PFS)] were compared, stratified by PD-L1 positivity. The prognostic role of PD-L1 was assessed using Kaplan–Meier, and univariate and multivariate Cox regression analyses.

Results

Pre-treatment, 46.2% and 6.8% of high-grade NMIBC demonstrated positive and high-level PD-L1 expression, respectively. Positive PD-L1 expression was associated with submucosal invasion and refractory-tumor recurrence. PD-L1 expression was not associated with RFS or PFS in regression analysis. Post-treatment, 55.1% and 11.6% of recurrent tumors demonstrated positive and high-level PD-L1 expression, respectively. Down-regulation of PD-L1 expression was noted in patients with refractory recurrence (p = 0.012).

Conclusion

Pre-treatment PD-L1 expression was associated with unfavorable pathological features in primary high-grade NMIBC and its expression level after BCG immunotherapy was significantly decreased in patients with refractory recurrence. PD-L1 expression did not have prognostic value for PFS or RFS; therefore, further research is necessary to identify novel biomarkers for prediction of disease outcomes in high-grade NMIBC.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

This study was funded by Hacettepe University (TR) (Grant number H.U. Scientific Research Projects Coordination Unit, TTU-2017_15644).

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Author notes

  1. Ahmet Murat Aydin

    Present address: Department of Genitourinary Oncology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA

Authors and Affiliations

  1. Department of Urology, Hacettepe University, Ankara, Turkey

    Ahmet Murat Aydin, Berk Hazir & Cenk Y. Bilen

  2. Department of Pathology, Koc University, Istanbul, Turkey

    Dilek E. Baydar

  3. Department of Pathology, Hacettepe University, Ankara, Turkey

    Berrin Babaoglu

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  1. Ahmet Murat Aydin
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Contributions

AMA: project development, data collection, data analysis, and manuscript writing. DEB: project development, data analysis, manuscript writing, and manuscript editing. BH: data collection. BB: data collection. CYB: project development, data analysis, and manuscript editing.

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Correspondence to Ahmet Murat Aydin.

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This study was conducted according to the Declaration of Helsinki and institutional review board approval (Approval no: GO 17/400-16) was obtained on May 30, 2017.

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Aydin, A.M., Baydar, D.E., Hazir, B. et al. Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy. World J Urol 38, 2537–2545 (2020). https://doi.org/10.1007/s00345-019-03065-2

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