Pretreatment PLR Is Preferable to NLR and LMR as a Predictor in Locally Advanced and Metastatic Bladder Cancer.

Background/Aim Advanced bladder cancer (BC) is associated with an inflammatory nature and poor prognosis Inflammatory biomarkers are potential predictors in BC. We conducted a study to assess the prognostic value of the pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in advanced bladder cancer. Patients and Methods A total of 226-patients with muscle-invasive BC (MIBC) were included. Overall (OS) and progression-free survival were estimated using the Kaplan-Meier method and the log-rank test was used for comparison. Univariate and multivariate Cox proportional hazard models were used to determine NLR, PLR, and LMR association with OS. Results Our patients' median progression-free survival and OS were 12.18 and 15.54 months, respectively. Receiver operating characteristic analysis revealed cut-off values for our chosen inflammatory markers. The patients with high NLR or PLR had inferior median OS compared to their counterparts with lower ratios for both (NLR: 22.51 vs. 9.84 months, respectively, p≤0.001; PLR: 17.68 vs. 14.08 months, respectively, p=0.08). Meanwhile, patients with low LMR had inferior median OS compared to patients with higher LMR (LMR: 20.14 months vs. 10.55 months, respectively, p<0.001). The multivariate Cox regression analysis identified a high PLR as an independent predictive factor of worse OS (hazard ratio=2.774, 95% confidence interval=1.486-5.178, p=0.001) but not NLR or LMR. Conclusion PLR, C-reactive protein-to-albumin ratio, and serum LDH levels, but not NLR and LMR, may function as independent predictors in patients with advanced BC prior to systemic treatment.

[1]  A. Kishan,et al.  NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022. , 2022, Journal of the National Comprehensive Cancer Network : JNCCN.

[2]  Xiaohe Tian,et al.  Tumor-associated neutrophils and neutrophil-targeted cancer therapies. , 2022, Biochimica et biophysica acta. Reviews on cancer.

[3]  M. Milowsky,et al.  The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma. , 2021, European urology.

[4]  N. Agarwal,et al.  A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors. , 2021, European urology oncology.

[5]  Jian Lu,et al.  Predictive value of preoperative lymphocyte-to-monocyte ratio on survival outcomes in bladder cancer patients after radical cystectomy , 2021, Journal of Cancer.

[6]  Chao-Yan Sun,et al.  Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer. , 2020, Urologic oncology.

[7]  V. Master,et al.  Risk stratification for bladder cancer: Biomarkers of inflammation and immune activation. , 2020, Urologic oncology.

[8]  X. Yao,et al.  The prognostic role of platelet-to-lymphocyte ratio on overall survival in gastric cancer: a systematic review and meta-analysis , 2020, BMC Gastroenterology.

[9]  Qin Liu,et al.  Prognostic Significance of the Lymphocyte-to-Monocyte Ratio in Bladder Cancer Undergoing Radical Cystectomy: A Meta-Analysis of 5638 Individuals , 2019, Disease markers.

[10]  F. Koga,et al.  Prognostic significance of serum γ-glutamyltransferase in patients with advanced urothelial carcinoma. , 2019, Urologic oncology.

[11]  J. Meeks,et al.  T1 bladder cancer: current considerations for diagnosis and management , 2018, Nature Reviews Urology.

[12]  Yuan Wu,et al.  Preoperative C-reactive protein/albumin ratio is a significant predictor of survival in bladder cancer patients after radical cystectomy: a retrospective study , 2018, Cancer management and research.

[13]  D. Takai,et al.  Mean platelet volume and lymphocyte-to-monocyte ratio are associated with shorter progression-free survival in EGFR-mutant lung adenocarcinoma treated by EGFR tyrosine kinase inhibitor , 2018, PloS one.

[14]  T. Shimura,et al.  Prognostic impact of preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer with special reference to myeloid-derived suppressor cells. , 2018, Fukushima journal of medical science.

[15]  S. Crabb,et al.  The Prognostic Role of the Change in Neutrophil-to-Lymphocyte Ratio During Neoadjuvant Chemotherapy in Patients with Muscle-Invasive Bladder Cancer: A Retrospective, Multi-Institutional Study , 2018, Bladder cancer.

[16]  Wei-min Li,et al.  The Neutrophil to Lymphocyte Ratio May Predict Benefit from Chemotherapy in Lung Cancer , 2018, Cellular Physiology and Biochemistry.

[17]  A. Mantovani,et al.  Roles of neutrophils in cancer growth and progression , 2017, Journal of leukocyte biology.

[18]  C. Stief,et al.  Prognostic Value of the Preoperative Platelet‐to‐leukocyte Ratio for Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer , 2017, Clinical genitourinary cancer.

[19]  A. Briganti,et al.  Prognostic Role of Neutrophil‐to‐Lymphocyte Ratio in Primary Non–muscle‐invasive Bladder Cancer , 2017, Clinical genitourinary cancer.

[20]  K. Shimada,et al.  Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy , 2017, Oncology.

[21]  Yan Ma,et al.  The prognostic value of C-reactive protein/albumin ratio in human malignancies: an updated meta-analysis , 2017, OncoTargets and therapy.

[22]  C. Compton,et al.  The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging , 2017, CA: a cancer journal for clinicians.

[23]  O. Buisán,et al.  Low Pretreatment Neutrophil‐to‐Lymphocyte Ratio Predicts for Good Outcomes in Patients Receiving Neoadjuvant Chemotherapy Before Radical Cystectomy for Muscle Invasive Bladder Cancer , 2017, Clinical genitourinary cancer.

[24]  A. Briganti,et al.  Lymphocyte‐to‐monocyte ratio and neutrophil‐to‐lymphocyte ratio as biomarkers for predicting lymph node metastasis and survival in patients treated with radical cystectomy , 2017, Journal of surgical oncology.

[25]  K. Pummer,et al.  Validation of the Preoperative Platelet-to-Lymphocyte Ratio as a Prognostic Factor in a European Cohort of Patients with Upper Tract Urothelial Carcinoma , 2016, Urologia Internationalis.

[26]  W. Hwang,et al.  Neutrophil‐to‐lymphocyte ratio as a bladder cancer biomarker: Assessing prognostic and predictive value in SWOG 8710 , 2016, Cancer.

[27]  J. Kennedy,et al.  Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[28]  J. Knox,et al.  Neutrophil-Lymphocyte Ratio and Pathological Response to Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer. , 2015, Clinical genitourinary cancer.

[29]  H. Kume,et al.  Pretreatment neutrophil‐to‐lymphocyte ratio as an independent predictor of survival in patients with metastatic urothelial carcinoma: A multi‐institutional study , 2015, International journal of urology : official journal of the Japanese Urological Association.

[30]  D. Ye,et al.  Preoperative lymphocyte-monocyte and platelet-lymphocyte ratios as predictors of overall survival in patients with bladder cancer undergoing radical cystectomy , 2015, Tumor Biology.

[31]  E. Scarpi,et al.  High Neutrophil-to-lymphocyte Ratio Persistent During First-line Chemotherapy Predicts Poor Clinical Outcome in Patients with Advanced Urothelial Cancer , 2015, Annals of Surgical Oncology.

[32]  O. Nativ,et al.  Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non-muscle-invasive bladder cancer. , 2015, Urologic oncology.

[33]  A. Zlotta,et al.  Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder , 2014, British Journal of Cancer.

[34]  J. Witjes,et al.  EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. , 2014, European urology.

[35]  C. Garlanda,et al.  Tumor associated macrophages and neutrophils in cancer. , 2013, Immunobiology.

[36]  M. Kuczyk,et al.  Serum C-reactive protein: a prognostic factor in metastatic urothelial cancer of the bladder , 2013, Medical Oncology.

[37]  A. Hemal,et al.  Preoperative neutrophil/lymphocyte ratio predicts overall survival and extravesical disease in patients undergoing radical cystectomy. , 2013, Journal of endourology.

[38]  Y. Horiguchi,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. , 2012, Urology.

[39]  M. Kastelan,et al.  Lymphocyte subsets, lymphocyte reactivity to mitogens, NK cell activity and neutrophil and monocyte phagocytic functions in patients with bladder carcinoma. , 2003, Anticancer research.

[40]  H. Nakazaki Preoperative and postoperative cytokines in patients with cancer , 1992, Cancer.

[41]  P. Grivas,et al.  Determinants of prognosis in metastatic urothelial carcinoma: a review of the literature , 2022, Journal of Cancer Metastasis and Treatment.

[42]  M. Inanc,et al.  Role of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Predictors Before Treatment for Metastatic Bladder Cancer Patients Receiving First-Line Chemotherapy , 2019 .

[43]  A. Jemal,et al.  Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. , 2017, European urology.

[44]  PhD Minyong Kang MD,et al.  The Prognostic Significance of the Early Postoperative Neutrophil-to-Lymphocyte Ratio in Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy , 2015, Annals of Surgical Oncology.

[45]  K. Tanabe,et al.  The role of Fas ligand and transforming growth factor beta in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy. , 2004, Cancer.