Skip to main content
Top
Published in: Annals of Surgical Oncology 4/2015

01-04-2015 | Urologic Oncology

High Neutrophil-to-lymphocyte Ratio Persistent During First-line Chemotherapy Predicts Poor Clinical Outcome in Patients with Advanced Urothelial Cancer

Authors: Lorena Rossi, MD, Matteo Santoni, MD, Simon J. Crabb, MD, PhD, Emanuela Scarpi, PhD, Luciano Burattini, MD, Caroline Chau, MD, Emanuela Bianchi, MD, Agnese Savini, MD, Salvatore L. Burgio, MD, Alessandro Conti, MD, Vincenza Conteduca, MD, Stefano Cascinu, MD, PhD, Ugo De Giorgi, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2015

Login to get access

Abstract

Background

Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer.

Methods

We retrospectively reviewed 292 patients with unresectable or metastatic urothelial cancer treated with first-line chemotherapy between January 2003 and December 2012. The cutoff values of NLR (>3 vs. <3) were evaluated before therapy and at day 1 of the second and third cycle (follow-up NLR). After univariate analysis, a multivariate analysis was carried out by Cox regression model and included the following variables: Eastern Cooperative Oncology Group (ECOG) performance status (≥2 vs. 0–1), visceral disease (present vs. absent), hemoglobin (<12 g/dL vs. >12 g/dL), pretherapy NLR (>3 vs. <3), and follow-up NLR (>3 vs. ≤3).

Results

Patients with pre- and follow-up NLR of >3 had a median progression-free survival of 3.2 months and a median overall survival of 5.7 months. In multivariate analysis, visceral metastases, pretherapy hemoglobin, and follow-up NLR were significant predictors of progression-free survival [hazard ratio (HR) 1.75, P = 0.0001; HR 1.57, P = 0.0015; HR 2.77, P < 0.0001, respectively], and of overall survival (HR 1.60, P = 0.0023; HR 1.59, P = 0.0024; HR 2.89, P < 0.0001, respectively); whereas pretherapy NLR remained as predictor of overall survival only (HR 1.53, P = 0.0101).

Conclusions

An increased NLR persistent during first-line chemotherapy is an independent predictive factor for patients with advanced urothelial cancer.
Literature
1.
go back to reference von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23:4602–8.CrossRefPubMed von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23:4602–8.CrossRefPubMed
2.
go back to reference Sternberg CN, de Mulder P, Schornagel JH, et al. EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006;42:50–4.CrossRefPubMed Sternberg CN, de Mulder P, Schornagel JH, et al. EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006;42:50–4.CrossRefPubMed
3.
go back to reference Galsky MD, Hahn NM, Rosenberg J, et al. Treatment of patients with metastatic urothelial cancer “unfit” for cisplatin-based chemotherapy. J Clin Oncol. 2011;29:2432–8.CrossRefPubMed Galsky MD, Hahn NM, Rosenberg J, et al. Treatment of patients with metastatic urothelial cancer “unfit” for cisplatin-based chemotherapy. J Clin Oncol. 2011;29:2432–8.CrossRefPubMed
4.
go back to reference De Santis M, Bellmunt J, Mead G, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012;30:191–9.CrossRefPubMedCentralPubMed De Santis M, Bellmunt J, Mead G, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012;30:191–9.CrossRefPubMedCentralPubMed
5.
go back to reference Galsky MD, Chen GJ, Oh WK, et al. Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann Oncol. 2012;23:406–10.CrossRefPubMed Galsky MD, Chen GJ, Oh WK, et al. Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann Oncol. 2012;23:406–10.CrossRefPubMed
6.
go back to reference Galsky MD, Hahn NM, Rosenberg J, et al. A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol. 2011;12:211–4.CrossRefPubMed Galsky MD, Hahn NM, Rosenberg J, et al. A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol. 2011;12:211–4.CrossRefPubMed
7.
go back to reference Castellano D, Carles J, Esteban E, et al. Recommendations for the optimal management of early and advanced urothelial carcinoma. Cancer Treat Rev. 2012;38:431–4.CrossRefPubMed Castellano D, Carles J, Esteban E, et al. Recommendations for the optimal management of early and advanced urothelial carcinoma. Cancer Treat Rev. 2012;38:431–4.CrossRefPubMed
8.
go back to reference Tsao CK, Gartrell BA, Oh WK, Galsky MD. Emerging personalized approaches for the management of advanced urothelial carcinoma. Expert Rev Anticancer Ther. 2012;12:1537–43.CrossRefPubMed Tsao CK, Gartrell BA, Oh WK, Galsky MD. Emerging personalized approaches for the management of advanced urothelial carcinoma. Expert Rev Anticancer Ther. 2012;12:1537–43.CrossRefPubMed
9.
go back to reference Galsky MD, Moshier E, Krege S, et al. Nomogram for predicting survival in patients with unresectable and/or metastatic urothelial cancer who are treated with cisplatin-based chemotherapy. Cancer. 2013;119:3012–9.CrossRefPubMed Galsky MD, Moshier E, Krege S, et al. Nomogram for predicting survival in patients with unresectable and/or metastatic urothelial cancer who are treated with cisplatin-based chemotherapy. Cancer. 2013;119:3012–9.CrossRefPubMed
10.
go back to reference Bellmunt J, Fougeray R, Rosenberg JE, et al. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Ann Oncol. 2013;24:1466–72.CrossRefPubMed Bellmunt J, Fougeray R, Rosenberg JE, et al. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Ann Oncol. 2013;24:1466–72.CrossRefPubMed
11.
go back to reference Bajorin DF, Dodd PM, Mazumdar M, et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol. 1999;17:3173–81.PubMed Bajorin DF, Dodd PM, Mazumdar M, et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol. 1999;17:3173–81.PubMed
12.
go back to reference Bellmunt J, Albanell J, Paz-Ares L, et al. Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine. Cancer. 2002;95:751–7.CrossRefPubMed Bellmunt J, Albanell J, Paz-Ares L, et al. Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine. Cancer. 2002;95:751–7.CrossRefPubMed
13.
go back to reference Balkwill F, Mantovani A. Cancer and inflammation: implications for pharmacology and therapeutics. Clin Pharmacol Ther. 2010;87:401–6.CrossRefPubMed Balkwill F, Mantovani A. Cancer and inflammation: implications for pharmacology and therapeutics. Clin Pharmacol Ther. 2010;87:401–6.CrossRefPubMed
14.
go back to reference Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.CrossRefPubMed Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.CrossRefPubMed
15.
go back to reference Guthrie GJ, Charlesb KA, Roxburgha CS, Horgana PG, McMillana DC, Clarkec SJ. The systemic inflammation-based neutrophil–lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88:218–30.CrossRefPubMed Guthrie GJ, Charlesb KA, Roxburgha CS, Horgana PG, McMillana DC, Clarkec SJ. The systemic inflammation-based neutrophil–lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88:218–30.CrossRefPubMed
16.
go back to reference Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124. Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124.
17.
go back to reference Teramukai S, Kitano T, Kishida Y, et al. Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer. 2009;45:1950–8.CrossRefPubMed Teramukai S, Kitano T, Kishida Y, et al. Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer. 2009;45:1950–8.CrossRefPubMed
18.
go back to reference Arrieta O, Michel Ortega RM, Villanueva-Rodríguez G, et al. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer. 2010;21;10:50.CrossRef Arrieta O, Michel Ortega RM, Villanueva-Rodríguez G, et al. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer. 2010;21;10:50.CrossRef
19.
go back to reference Kishi Y, Kopetz S, Chun YS, Palavecino M, Abdalla EK, Vauthey JN. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol. 2009;16:614–22.CrossRefPubMed Kishi Y, Kopetz S, Chun YS, Palavecino M, Abdalla EK, Vauthey JN. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol. 2009;16:614–22.CrossRefPubMed
20.
go back to reference Azab B, Bhatt VR, Phookan J, et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol. 2012;19:217–24.CrossRefPubMed Azab B, Bhatt VR, Phookan J, et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol. 2012;19:217–24.CrossRefPubMed
21.
go back to reference Santoni M, De Giorgi U, Iacovelli R, et al. Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma. Br J Cancer. 2013;109:1755–9.CrossRefPubMedCentralPubMed Santoni M, De Giorgi U, Iacovelli R, et al. Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma. Br J Cancer. 2013;109:1755–9.CrossRefPubMedCentralPubMed
22.
go back to reference Leibowitz-Amit R, Templeton AJ, Omlin A, et al. Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2014;25:657–62.CrossRefPubMed Leibowitz-Amit R, Templeton AJ, Omlin A, et al. Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2014;25:657–62.CrossRefPubMed
23.
go back to reference Sharaiha RZ, Halazun KJ, Mirza F, et al. Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann Surg Oncol. 2011;18:3362–9.CrossRefPubMedCentralPubMed Sharaiha RZ, Halazun KJ, Mirza F, et al. Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann Surg Oncol. 2011;18:3362–9.CrossRefPubMedCentralPubMed
24.
go back to reference Azuma T, Matayoshi Y, Odani K, et al. Preoperative neutrophil-lymphocyte ratio as an independent prognostic marker for patients with upper urinary tract urothelial carcinoma. Clin Genitourin Cancer. 2013;11:337–41.CrossRefPubMed Azuma T, Matayoshi Y, Odani K, et al. Preoperative neutrophil-lymphocyte ratio as an independent prognostic marker for patients with upper urinary tract urothelial carcinoma. Clin Genitourin Cancer. 2013;11:337–41.CrossRefPubMed
25.
go back to reference Krane LS, Richards KA, Kader AK, Davis R, Balaji KC, Hemal AK. Preoperative neutrophil lymphocyte ratio predicts overall survival and extravescical disease in patients undergoing radical cystectomy. J Endourol. 2013,27:1046–50.CrossRefPubMed Krane LS, Richards KA, Kader AK, Davis R, Balaji KC, Hemal AK. Preoperative neutrophil lymphocyte ratio predicts overall survival and extravescical disease in patients undergoing radical cystectomy. J Endourol. 2013,27:1046–50.CrossRefPubMed
26.
go back to reference Hermanns T, Bhindi B, Wei Y, et al. Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. Br J Cancer. 2014;111:444–51.CrossRefPubMed Hermanns T, Bhindi B, Wei Y, et al. Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. Br J Cancer. 2014;111:444–51.CrossRefPubMed
27.
go back to reference Tanaka N, Kikuchi E, Kanao K, et al. A multi-institutional validation of the prognostic value of the neutrophil-to-lymphocyte ratio for upper tract urothelial carcinoma Treated with radical nephroureterectomy. Ann Surg Oncol. doi:10.1245/s10434-014-3830-3. Tanaka N, Kikuchi E, Kanao K, et al. A multi-institutional validation of the prognostic value of the neutrophil-to-lymphocyte ratio for upper tract urothelial carcinoma Treated with radical nephroureterectomy. Ann Surg Oncol. doi:10.​1245/​s10434-014-3830-3.
28.
go back to reference Gondo T, Nakashima J, Ohno Y, et al. Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology. 2012;79:1085–91.CrossRefPubMed Gondo T, Nakashima J, Ohno Y, et al. Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology. 2012;79:1085–91.CrossRefPubMed
29.
go back to reference Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13:871–82.CrossRef Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13:871–82.CrossRef
30.
go back to reference Kastelan Z, Lukac J, Derezić D, et al. Lymphocyte subsets, lymphocyte reactivity to mitogens, NK cell activity and neutrophil and monocyte phagocytic functions in patients with bladder carcinoma. Anticancer Res. 2003;23:5185–9.PubMed Kastelan Z, Lukac J, Derezić D, et al. Lymphocyte subsets, lymphocyte reactivity to mitogens, NK cell activity and neutrophil and monocyte phagocytic functions in patients with bladder carcinoma. Anticancer Res. 2003;23:5185–9.PubMed
31.
go back to reference Eruslanov E, Stoffs T, Kim WJ, et al. Expansion of CCR8+ inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas. Clin Cancer Res. 2013;19:1670–80.CrossRefPubMedCentralPubMed Eruslanov E, Stoffs T, Kim WJ, et al. Expansion of CCR8+ inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas. Clin Cancer Res. 2013;19:1670–80.CrossRefPubMedCentralPubMed
32.
go back to reference De Giorgi U, Mego M, Scarpi E, et al. Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in metastatic breast cancer. Clin Breast Cancer. 2012;12:264–9.CrossRefPubMed De Giorgi U, Mego M, Scarpi E, et al. Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in metastatic breast cancer. Clin Breast Cancer. 2012;12:264–9.CrossRefPubMed
33.
go back to reference Ray-Coquard I, Cropet C, Van Glabbeke M, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69:5383–91.CrossRefPubMedCentralPubMed Ray-Coquard I, Cropet C, Van Glabbeke M, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69:5383–91.CrossRefPubMedCentralPubMed
Metadata
Title
High Neutrophil-to-lymphocyte Ratio Persistent During First-line Chemotherapy Predicts Poor Clinical Outcome in Patients with Advanced Urothelial Cancer
Authors
Lorena Rossi, MD
Matteo Santoni, MD
Simon J. Crabb, MD, PhD
Emanuela Scarpi, PhD
Luciano Burattini, MD
Caroline Chau, MD
Emanuela Bianchi, MD
Agnese Savini, MD
Salvatore L. Burgio, MD
Alessandro Conti, MD
Vincenza Conteduca, MD
Stefano Cascinu, MD, PhD
Ugo De Giorgi, MD, PhD
Publication date
01-04-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 4/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-4097-4

Other articles of this Issue 4/2015

Annals of Surgical Oncology 4/2015 Go to the issue