The prognostic value of the neutrophil-to-lymphocyte ratio in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy

Anna J Black; Homayoun Zargar; Kamran Zargar-Shoshtari; Adrian S Fairey; Laura S Mertens; Colin P Dinney; Maria C Mir; Laura-Maria Krabbe; Michael S Cookson; Niels-Erik Jacobsen; Joshua Griffin; Jeffrey S Montgomery; Nikhil Vasdev; Evan Y Yu; Evanguelos Xylinas; Nicholas J Campain; Wassim Kassouf; Marc A Dall'Era; Jo-An Seah; Cesar E Ercole; Simon Horenblas; John S McGrath; Jonathan Aning; Shahrokh F Shariat; Jonathan L Wright; Andrew C Thorpe; Todd M Morgan; Jeff M Holzbeierlein; Trinity J Bivalacqua; Scott North; Daniel A Barocas; Yair Lotan; Petros Grivas; Andrew J Stephenson; Jay B Shah; Bas W van Rhijn; Philippe E Spiess; Siamak Daneshmand; Srikala S Sridhar; Peter C Black

doi:10.1016/j.urolonc.2019.09.023

The prognostic value of the neutrophil-to-lymphocyte ratio in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy

Urol Oncol. 2020 Jan;38(1):3.e17-3.e27. doi: 10.1016/j.urolonc.2019.09.023. Epub 2019 Oct 31.

Authors

Anna J Black¹, Homayoun Zargar², Kamran Zargar-Shoshtari³, Adrian S Fairey⁴, Laura S Mertens⁵, Colin P Dinney⁶, Maria C Mir⁷, Laura-Maria Krabbe⁸, Michael S Cookson⁹, Niels-Erik Jacobsen⁴, Joshua Griffin¹⁰, Jeffrey S Montgomery¹¹, Nikhil Vasdev¹², Evan Y Yu¹³, Evanguelos Xylinas¹⁴, Nicholas J Campain¹⁵, Wassim Kassouf¹⁶, Marc A Dall'Era¹⁷, Jo-An Seah¹⁸, Cesar E Ercole¹⁹, Simon Horenblas⁵, John S McGrath¹⁵, Jonathan Aning²⁰, Shahrokh F Shariat²¹, Jonathan L Wright²², Andrew C Thorpe²³, Todd M Morgan¹¹, Jeff M Holzbeierlein¹⁰, Trinity J Bivalacqua²⁴, Scott North²⁵, Daniel A Barocas²⁶, Yair Lotan²⁷, Petros Grivas²⁸, Andrew J Stephenson¹⁹, Jay B Shah²⁹, Bas W van Rhijn⁵, Philippe E Spiess³⁰, Siamak Daneshmand³¹, Srikala S Sridhar¹⁸, Peter C Black³²

Affiliations

¹ Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
² Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada; Western Health, Melbourne, Australia.
³ Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa FL; University of Auckland, Auckland, New Zealand.
⁴ University of Alberta, Edmonton, AB, Canada.
⁵ Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
⁶ Department of Urology, MD Anderson Cancer Center, Houston, TX.
⁷ Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH; Department of Urology, Fundacion Instituto Valenciano de Oncologia, Valencia, Spain.
⁸ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, University of Münster, Münster, Germany.
⁹ Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK.
¹⁰ Department of Urology, University of Kansas Medical Center, Kansas City, KS.
¹¹ Department of Urology, University of Michigan Health System, Ann Arbor, MI.
¹² Hertfordshire and Bedfordshire Urological Cancer Centre, Department of Urology, Lister Hospital, Stevenage, UK; Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK.
¹³ Department of Medicine, Division of Oncology, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA.
¹⁴ Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY; Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France.
¹⁵ Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK.
¹⁶ Department of Surgery (Division of Urology), McGill University Health Center, Montreal, Canada.
¹⁷ Department of Urology, University of California at Davis, Davis Medical Center, Sacramento, CA.
¹⁸ Princess Margaret Hospital, Toronto, ON, Canada.
¹⁹ Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
²⁰ Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK; Bristol Urological Institute, North Bristol NHS Trust, Bristol, UK.
²¹ Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY; Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
²² Department of Urology, University of Washington, Seattle, WA.
²³ Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK.
²⁴ Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
²⁵ Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, University of Alberta, AB, Canada.
²⁶ Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN.
²⁷ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
²⁸ Department of Medicine, Division of Oncology, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic.
²⁹ Department of Urology, MD Anderson Cancer Center, Houston, TX; Department of Urology, Stanford University School of Medicine, Stanford, CA.
³⁰ Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa FL.
³¹ USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, CA.
³² Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. Electronic address: [email protected].

PMID: 31676278
DOI: 10.1016/j.urolonc.2019.09.023

Abstract

Introduction: The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC.

Methods: A retrospective analysis was performed on patients with nonmetastatic MIBC (cT2-4aN0M0) who received NAC prior to RC between 2000 and 2013 at 1 of 19 centers across Europe and North America. The pre-NAC NLR was used to split patients into a low (NLR ≤ 3) and high (NLR > 3) group. Demographic and clinical parameters were compared between the groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors for disease-specific and overall survival were analyzed using Cox regression, while predictors of response to NAC (defined as absence of MIBC in RC specimen) were investigated using logistic regression.

Results: Data were available for 340 patients (199 NLR ≤ 3, 141 NLR > 3). Other than age and rate of lymphovascular invasion, demographic and pretreatment characteristics did not differ significantly. More patients in the NLR > 3 group had residual MIBC after NAC than the NLR ≤ 3 group (70.8% vs. 58.3%, P = 0.049). NLR was the only significant predictor of response (odds ratio: 0.36, P = 0.003) in logistic regression. NLR was a significant risk factor for both disease-specific (hazard ratio (HR): 2.4, P = 0.006) and overall survival (HR:1.8, P = 0.02).

Conclusion: NLR > 3 was associated with a decreased response to NAC and shorter disease-specific and overall survival. This suggests that NLR is a simple tool that can aid in MIBC risk stratification in clinical practice.

Keywords: MIBC; NLR; Neoadjuvant chemotherapy; Radical cystectomy; Urothelial carcinoma.

MeSH terms

Cystectomy / methods*
Female
Humans
Lymphocytes / metabolism*
Male
Middle Aged
Neoadjuvant Therapy / methods*
Neutrophils / metabolism*
Prognosis
Retrospective Studies
Urinary Bladder Neoplasms / blood
Urinary Bladder Neoplasms / drug therapy*
Urinary Bladder Neoplasms / surgery*