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Positive Ki-67 and PD-L1 expression in post-neoadjuvant chemotherapy muscle-invasive bladder cancer is associated with shorter overall survival: a retrospective study

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Abstract

Purpose

There is an unmet need to develop prognostic biomarkers in post-neoadjuvant chemotherapy (NAC) muscle-invasive bladder cancer (MIBC) patients. We examine whether Ki-67 and PD-L1 expression can be used to guide adjuvant therapy.

Methods

Tissue microarrays were constructed from 130 post-NAC radical cystectomy samples. Up to 5 cores per sample were included. Expressions of Ki-67 and PD-L1 were evaluated using immunohistochemistry (IHC).

Results

Using a Cox regression model, positive Ki-67 expression in post-NAC radical cystectomy samples was associated with poorer overall survival (OS) (HR = 2.412, 95% CI, 1.076–5.408), independent of the pathological lymph node/N-stage. Positive Ki-67 expression was also associated with lack of tumor downstaging in a multivariable logistic regression model analysis (OR = 0.081, 95% CI, 0.014–0.464). PD-L1− and PD-L1+ expression was associated with a median OS of 49.8 months and 26.9 months, respectively, which did not reach statistical significance. Patients with Ki-67/PD-L1 double-negative tumors had a significantly longer median OS of 98.2 months versus 29.9 and 26.9 months in PD-L1−/Ki-67+ and PD-L1+/Ki-67+ tumors, respectively. Lack of tumor downstaging was significantly associated with positive Ki-67 and positive PD-L1 expression.

Conclusion

Positive Ki-67 and PD-L1 expression in post-NAC radical cystectomy samples was associated with inferior OS and absence of tumor downstaging. IHC on Ki-67 and PD-L1 would help to select patients for adjuvant therapy in post-NAC muscle-invasive bladder cancer.

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Abbreviations

MIBC:

Muscle-invasive bladder cancer

MVAC:

Methotrexate, Vinblastine, Doxorubicin/Adriamycin, Cisplatin

NAC:

Neoadjuvant chemotherapy

OS:

Overall survival

TMA:

Tissue microarray

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Acknowledgements

Dr. Alex Lopez performed pathological scoring of immunohistochemistry on AR and Ki-67. This work is supported in part by the Moffitt’s Tissue Core performed fixing and IHC staining, and Biostatistics and Bioinformatics Shared Resources at the H. Lee Moffitt Cancer Center & Research Institute, an NCI-designated Comprehensive Cancer Center (P30-CA076292). We thank them for their help. Editorial assistance was provided by the Moffitt Cancer Center’s Scientific Editing Department by Dr. Paul Fletcher & Daley Drucker. No compensation was given beyond their regular salaries.

Funding

This study is funded by Moffitt’s internal research support to Jingsong Zhang.

Author information

Authors and Affiliations

  1. Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Selene Rubino

  2. Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Youngchul Kim & Junmin Zhou

  3. Department of Pathology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Jasreman Dhilon

  4. Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, WCB-GU, Tampa, FL, 33612, USA

    Roger Li, Philippe Spiess, Michael Poch, Brandon J. Manley, Julio Pow-Sang, Scott Gilbert, Wade Sexton & Jingsong Zhang

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  1. Selene Rubino
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  2. Youngchul Kim
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  3. Junmin Zhou
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  11. Wade Sexton
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  12. Jingsong Zhang
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Contributions

SR: data collection and manuscript writing; YK and JZ: data analysis and manuscript writing; JD: data collection; RL, PS, MP, BJM, JP, SG, and WS: data collection and manuscript editing; JZ: project development, data management, data analysis and manuscript writing.

Corresponding author

Correspondence to Jingsong Zhang.

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Conflict of interest

Dr. Zhang has received honoraria for advisory board or speaker program from AstraZeneca, Merck and Seattle Genetics.

Ethics approval and consent to participate

This study qualified for expedited approval under the federal regulations at 45CFR46.116(d) per the USF Institutional Review Board, IRB #Pro00015860.

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Rubino, S., Kim, Y., Zhou, J. et al. Positive Ki-67 and PD-L1 expression in post-neoadjuvant chemotherapy muscle-invasive bladder cancer is associated with shorter overall survival: a retrospective study. World J Urol 39, 1539–1547 (2021). https://doi.org/10.1007/s00345-020-03342-5

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  • DOI: https://doi.org/10.1007/s00345-020-03342-5

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