Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancerCitation formats

TY - JOUR

T1 - Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer

AU - Joseph, N

AU - Dovedi, S J

AU - Thompson, C

AU - Lyons, J

AU - Kennedy, J

AU - Elliott, T

AU - West, C M

AU - Choudhury, A

N1 - © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2016/2

Y1 - 2016/2

N2 - BACKGROUND: Pre-treatment lymphocytopaenia may result from cytokines secreted by the tumour microenvironment in association with aggressive tumour biology. We sought to establish the prognostic significance of lymphocytopaenia in muscle-invasive and advanced bladder cancer.PATIENTS AND METHODS: Seventy-four patients with muscle-invasive bladder cancer treated with radical chemoradiotherapy and 131 patients with advanced bladder cancer treated with palliative chemotherapy were included in the study. The absolute lymphocyte count on the first day of treatment was recorded. Invasive local or systemic recurrence in the muscle-invasive bladder cancer cohort and all-cause mortality in the advanced bladder cancer cohort were defined as survival end points. Receiver operating characteristic (ROC) curve analysis was utilized to determine the cut-off for defining lymphocytopaenia in the muscle-invasive bladder cancer cohort followed by multivariable analysis in a model evaluating the following variables: anaemia, neutrophilia, tumour stage, hydronephrosis and neoadjuvant chemotherapy. Subsequently, lymphocytopaenia was assessed in a multivariable model of the advanced bladder cancer cohort analysing the following prognostic variables: neutrophilia, anaemia, performance status and presence of bone or visceral metastases. A further analysis was carried out evaluating absolute lymphocyte count as a continuous variable.RESULTS: An absolute lymphocyte count of 1.5 × 10(9)/l was determined as the cut-off on ROC curve analysis in the muscle-invasive bladder cancer cohort, and multivariate analysis revealed that only lymphocytopaenia was predictive for inferior outcome in this cohort. In the advanced bladder cancer cohort, lymphocytopaenia [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.4; P = 0.02] and performance status (HR 1.7, 95% CI 1.0-2.7; P = 0.047) were adverse prognostic factors in the binary variable multivariate model. Absolute lymphocyte count was the sole significant factor when analysed as a continuous variable (HR 0.66, 95% CI 0.5-0.87; P = 0.003).CONCLUSION: Pre-treatment lymphocytopaenia is an independent adverse prognostic factor in both muscle-invasive and advanced bladder cancer. It may be a manifestation of cancer-induced immune suppression driving tumour progression.

AB - BACKGROUND: Pre-treatment lymphocytopaenia may result from cytokines secreted by the tumour microenvironment in association with aggressive tumour biology. We sought to establish the prognostic significance of lymphocytopaenia in muscle-invasive and advanced bladder cancer.PATIENTS AND METHODS: Seventy-four patients with muscle-invasive bladder cancer treated with radical chemoradiotherapy and 131 patients with advanced bladder cancer treated with palliative chemotherapy were included in the study. The absolute lymphocyte count on the first day of treatment was recorded. Invasive local or systemic recurrence in the muscle-invasive bladder cancer cohort and all-cause mortality in the advanced bladder cancer cohort were defined as survival end points. Receiver operating characteristic (ROC) curve analysis was utilized to determine the cut-off for defining lymphocytopaenia in the muscle-invasive bladder cancer cohort followed by multivariable analysis in a model evaluating the following variables: anaemia, neutrophilia, tumour stage, hydronephrosis and neoadjuvant chemotherapy. Subsequently, lymphocytopaenia was assessed in a multivariable model of the advanced bladder cancer cohort analysing the following prognostic variables: neutrophilia, anaemia, performance status and presence of bone or visceral metastases. A further analysis was carried out evaluating absolute lymphocyte count as a continuous variable.RESULTS: An absolute lymphocyte count of 1.5 × 10(9)/l was determined as the cut-off on ROC curve analysis in the muscle-invasive bladder cancer cohort, and multivariate analysis revealed that only lymphocytopaenia was predictive for inferior outcome in this cohort. In the advanced bladder cancer cohort, lymphocytopaenia [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.4; P = 0.02] and performance status (HR 1.7, 95% CI 1.0-2.7; P = 0.047) were adverse prognostic factors in the binary variable multivariate model. Absolute lymphocyte count was the sole significant factor when analysed as a continuous variable (HR 0.66, 95% CI 0.5-0.87; P = 0.003).CONCLUSION: Pre-treatment lymphocytopaenia is an independent adverse prognostic factor in both muscle-invasive and advanced bladder cancer. It may be a manifestation of cancer-induced immune suppression driving tumour progression.

KW - Aged

KW - Aged, 80 and over

KW - Anemia

KW - Biomarkers, Tumor

KW - Bone Neoplasms

KW - Chemoradiotherapy

KW - Cohort Studies

KW - Female

KW - Humans

KW - Hydronephrosis

KW - Lymphocyte Count

KW - Lymphopenia

KW - Male

KW - Middle Aged

KW - Muscle Neoplasms

KW - Neoplasm Recurrence, Local

KW - Neutrophils

KW - Prognosis

KW - ROC Curve

KW - Tumor Microenvironment

KW - Urinary Bladder

KW - Urinary Bladder Neoplasms

KW - Journal Article

U2 - 10.1093/annonc/mdv546

DO - 10.1093/annonc/mdv546

M3 - Article

C2 - 26578732

VL - 27

SP - 294

EP - 299

JO - Annals of oncology : official journal of the European Society for Medical Oncology / ESMO

JF - Annals of oncology : official journal of the European Society for Medical Oncology / ESMO

SN - 0923-7534

IS - 2

ER -