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Neutrophil-to-lymphocyte ratio and lactate dehydrogenase as biomarkers for urothelial cancer treated with immunotherapy

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Abstract

Purpose

To identify patients with metastatic urothelial cancer (mUC) unlikely to benefit from immune-checkpoint inhibitors (ICIs).

Methods/Patients

We explored the predictive and prognostic values of baseline neutrophil-to-lymphocyte ratio (NLR), with cut-offs ≥ 3 and ≥ 5, and of a urothelial immune prognostic index (UIPI, based on increased NLR and LDH), on 146 patients.

Results

NLR and UIPI significantly predicted progressive disease and progression-free survival with both cut-offs (p = 0.0069, p = 0.0034, p = 0.0160, p = 0.0063; p < 0.001, p = 0.021, p = 0.014, p = 0.026; for NLR-3, NLR-5, UIPI-3, UIPI-5, respectively) and overall survival when NLR cut-off was ≥ 5 (p = 0.03 and p = 0.024, for NLR-5 and UIPI-5, respectively).

Conclusions

NLR-5 deserves prospective validation to identify mUC patients with poor prognosis following ICIs.

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Acknowledgements

We thank all patients that participated in the study, all involved clinicians and study nurses and the Mediterranean Cancer Support and Rehabilitation (Medicare Onlus) no-profit association for the support to data management.

Funding

None.

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Cannizzaro Hospital, Catania, Italy

    G. L. Banna & H. Lipari

  2. Deparment of Oncology, United Lincolnshire NHS Hospital Trust, Lincoln, UK

    G. L. Banna

  3. Department of Clinical and Experimental Medicine, University of Catania, Cannizzaro Hospital, Catania, Italy

    R. Di Quattro, L. Malatino & V. Urzia

  4. Medical Oncology Unit, Ospedale Policlinico San Martino, Genoa, Italy

    G. Fornarini

  5. Oncology Department, Geneva University Hospital, Geneva, Switzerland

    A. Addeo

  6. Medical Oncology Unit 1, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy

    M. Maruzzo & U. Basso

  7. STMicroelectronics ADG Central R&D, Catania, Italy

    F. Rundo

  8. Istituto Scientifico Romagnolo per io Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, FC, Italy

    U. De Giorgi

Authors
  1. G. L. Banna
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  2. R. Di Quattro
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  3. L. Malatino
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  4. G. Fornarini
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  5. A. Addeo
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  6. M. Maruzzo
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  7. V. Urzia
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  8. F. Rundo
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  9. H. Lipari
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  10. U. De Giorgi
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Contributions

GLB, LM, UDG, UB, GF contributed to study concept and design; RDQ, AA, MM, VU, FR, HL to data acquisition; GLB, LM, UDG, UB to data analysis and interpretation; GLB, RDQ, LM to manuscript drafting; UDG, UB, GF to manuscript critical revision for important intellectual content; GLB, RDQ, GF to statistical analysis; VU, HL to administrative, technical or material support; LM to supervision. All authors contributed to the interpretation of data and to the revision of the manuscript.

Corresponding author

Correspondence to U. De Giorgi.

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Conflicts of interest

The authors declare no competing interests.

Ethical approval

The authors state that they have obtained appropriate institutional review board approval and have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Informed consent

Informed consent has been obtained from the participants involved.

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Electronic supplementary material

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12094_2020_2337_MOESM1_ESM.ppt

Supplementary Figure 1. Overall and Progression-Free Survival according to disease response (DCR versus PD): A) OS; B) PFS. (PPT 90 kb)

12094_2020_2337_MOESM2_ESM.ppt

Supplementary Figure 2. Receiver operating characteristic (ROC) curve (A) and dot histogram (B) of NLR based on PD: ROC curve area is 0.67 (95% CI, 0.58-0.75) (p=0.0006), best cut-off 4,6 (sensitivity 0.51, specificity 0.81). (PPT 89 kb)

12094_2020_2337_MOESM3_ESM.ppt

Supplementary Figure 3. Overall and Progression-Free Survival in patients with NLR-5 according to the three Center series, Padua (n=21), Catania (=22), Meldola (n=3): A) OS; Padua (median 3.0; 95% CI, 1.8-4.2), Catania (median 4.8; 95% CI, 3.4-13.0), Meldola (median 3.4; 95% CI, 0.4-7.1) (p=0.658); B) PFS; Padua (median 2.3; 95% CI, 1.0-3.6), Catania (median 2.5; 95% CI, 1.4-3.6), Meldola (median 1.8; 95% CI, 0.3-3.9) (p=0.210). Abbreviations: CR, complete response; DCR, disease control rate (=CR+PR+SD); NLR-3, neutrophils-to-lymphocytes ratio ≥ 3; NLR-5, neutrophils-to-lymphocytes ratio ≥ 5; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; UIPI, urothelial immune prognostic index; UIPI-3, NLR ≥ 3 and lactate dehydrogenase upper the normal value; UIPI-5, NLR ≥ 5 and lactate dehydrogenase upper the normal value. (PPT 101 kb)

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Banna, G.L., Di Quattro, R., Malatino, L. et al. Neutrophil-to-lymphocyte ratio and lactate dehydrogenase as biomarkers for urothelial cancer treated with immunotherapy. Clin Transl Oncol 22, 2130–2135 (2020). https://doi.org/10.1007/s12094-020-02337-3

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  • DOI: https://doi.org/10.1007/s12094-020-02337-3

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