Survival outcomes after radical cystectomy (RC) for bladder cancer (BCa) have not improved in recent decades; nevertheless, RC remains the standard treatment for patients with localized muscle-invasive BCa. Identification of the patients most likely to benefit from RC only versus a combination with systemic therapy versus systemic therapy first/only and bladder-sparing is needed. This systematic review and meta-analysis pools the data from published studies on blood-based biomarkers to help prognosticate disease recurrence after RC. A literature search on PubMed and Scopus was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Articles published before November 2022 were screened for eligibility. A meta-analysis was performed on studies investigating the association of the neutrophil-to-lymphocyte ratio (NLR), the only biomarker with sufficient data, with recurrence-free survival. The systematic review identified 33 studies, and 7 articles were included in the meta-analysis. Our results demonstrated a statistically significant correlation between elevated NLR and an increased risk of disease recurrence (HR 1.26; 95% CI 1.09, 1.45; p = 0.002) after RC. The systematic review identified various other inflammatory biomarkers, such as interleukin-6 or the albumin-to-globulin ratio, which have been reported to have a prognostic impact on recurrence after RC. Besides that, the nutritional status, factors of angiogenesis and circulating tumor cells, and DNA seem to be promising tools for the prognostication of recurrence after RC. Due to the high heterogeneity between the studies and the different cut-off values of biomarkers, prospective and validation trials with larger sample sizes and standardized cut-off values should be conducted to strengthen the approach in using biomarkers as a tool for risk stratification in clinical decision-making for patients with localized muscle-invasive BCa.

Department of Urology 2nd Faculty of Medicine Charles University 150 06 Prague Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna 1090 Vienna Austria

Department of Urology University of Texas Southwestern Medical Center Dallas TX 75390 USA

Department of Urology Weill Cornell Medical College New York NY 10065 USA

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman 19328 Jordan

Institute for Urology and Reproductive Health Sechenov University 119991 Moscow Russia

Karl Landsteiner Institute of Urology and Andrology 1090 Vienna Austria

See more in PubMed

Xylinas E., Robinson B., Kluth L., Volkmer B., Hautmann R., Küfer R., Zerbib M., Kwon E., Thompson R., Boorjian S., et al. Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. Eur. J. Surg. Oncol. EJSO. 2014;40:121–127. doi: 10.1016/j.ejso.2013.08.023. PubMed DOI

Shariat S.F., Karakiewicz P.I., Palapattu G.S., Lotan Y., Rogers C.G., Amiel G.E., Vazina A., Gupta A., Bastian P.J., Sagalowsky A.I., et al. Outcomes of Radical Cystectomy for Transitional Cell Carcinoma of the Bladder: A Contemporary Series from the Bladder Cancer Research Consortium. Pt 1J. Urol. 2006;176:2414–2422;. doi: 10.1016/j.juro.2006.08.004. PubMed DOI

Aziz A., May M., Burger M., Palisaar R.-J., Trinh Q.-D., Fritsche H.-M., Rink M., Chun F., Martini T., Bolenz C., et al. Prediction of 90-day Mortality after Radical Cystectomy for Bladder Cancer in a Prospective European Multicenter Cohort. Eur. Urol. 2014;66:156–163. doi: 10.1016/j.eururo.2013.12.018. PubMed DOI

Stein J.P., Lieskovsky G., Cote R., Groshen S., Feng A.-C., Boyd S., Skinner E., Bochner B., Thangathurai D., Mikhail M., et al. Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1054 Patients. J. Clin. Oncol. 2001;19:666–675. doi: 10.1200/JCO.2001.19.3.666. PubMed DOI

Shariat S.F., Ashfaq R., Karakiewicz P.I., Saeedi O., Sagalowsky A.I., Lotan Y. Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer. 2007;109:1106–1113. doi: 10.1002/cncr.22521. PubMed DOI

Kluth L.A., Black P.C., Bochner B.H., Catto J., Lerner S.P., Stenzl A., Sylvester R., Vickers A.J., Xylinas E., Shariat S.F. Prognostic and Prediction Tools in Bladder Cancer: A Comprehensive Review of the Literature. Eur. Urol. 2015;68:238–253. doi: 10.1016/j.eururo.2015.01.032. PubMed DOI

Shariat S.F., Zlotta A.R., Ashfaq R., Sagalowsky A.I., Lotan Y. Cooperative effect of cell-cycle regulators expression on bladder cancer development and biologic aggressiveness. Mod. Pathol. 2007;20:445–459. doi: 10.1038/modpathol.3800757. PubMed DOI

Mathieu R., Lucca I., Rouprêt M., Briganti A., Shariat S.F. The prognostic role of lymphovascular invasion in urothelial carcinoma of the bladder. Nat. Rev. Urol. 2016;13:471–479. doi: 10.1038/nrurol.2016.126. PubMed DOI

Moschini M., D’Andrea D., Korn S., Irmak Y., Soria F., Compérat E., Shariat S.F. Characteristics and clinical significance of histological variants of bladder cancer. Nat. Rev. Urol. 2017;14:651–668. doi: 10.1038/nrurol.2017.125. PubMed DOI

Svatek R.S., Shariat S.F., Lasky R.E., Skinner E.C., Novara G., Lerner S.P., Fradet Y., Bastian P.J., Kassouf W., Karakiewicz P.I., et al. The Effectiveness of Off-Protocol Adjuvant Chemotherapy for Patients with Urothelial Carcinoma of the Urinary Bladder. Clin. Cancer Res. 2010;16:4461–4467. doi: 10.1158/1078-0432.CCR-10-0457. PubMed DOI

Isbarn H., Jeldres C., Zini L., Perrotte P., Baillargeon-Gagne S., Capitanio U., Shariat S.F., Arjane P., Saad F., McCormack M., et al. A Population Based Assessment of Perioperative Mortality After Cystectomy for Bladder Cancer. J. Urol. 2009;182:70–77. doi: 10.1016/j.juro.2009.02.120. PubMed DOI

Grossmann N.C., Rajwa P., Quhal F., König F., Mostafaei H., Laukhtina E., Mori K., Katayama S., Motlagh R.S., Fankhauser C.D., et al. Comparative Outcomes of Primary versus Recurrent High-risk Non–muscle-invasive and Primary versus Secondary Muscle-invasive Bladder Cancer after Radical Cystectomy: Results from a Retrospective Multicenter Study. Eur. Urol. Open Sci. 2022;39:14–21. doi: 10.1016/j.euros.2022.02.011. PubMed DOI PMC

Necchi A., Pond G.R., Moschini M., Plimack E.R., Niegisch G., Yu E.Y., Bamias A., Agarwal N., Vaishampayan U., Theodore C., et al. Development of a Prediction Tool for Exclusive Locoregional Recurrence after Radical Cystectomy in Patients with Muscle-Invasive Bladder Cancer. Clin. Genitourin. Cancer. 2019;17:7–14.e3. doi: 10.1016/j.clgc.2018.09.008. PubMed DOI PMC

Ru Y., Dancik G.M., Theodorescu D. Biomarkers for prognosis and treatment selection in advanced bladder cancer patients. Curr. Opin. Urol. 2011;21:420–427. doi: 10.1097/MOU.0b013e32834956d6. PubMed DOI PMC

Shariat S.F., Lotan Y., Vickers A., Karakiewicz P.I., Schmitz-Dräger B.J., Goebell P.J., Malats N. Statistical consideration for clinical biomarker research in bladder cancer. Urol. Oncol. Semin. Orig. Investig. 2010;28:389–400. doi: 10.1016/j.urolonc.2010.02.011. PubMed DOI PMC

Bensalah K., Montorsi F., Shariat S.F. Challenges of Cancer Biomarker Profiling. Eur. Urol. 2007;52:1601–1609. doi: 10.1016/j.eururo.2007.09.036. PubMed DOI

Gakis G. The Role of Inflammation in Bladder Cancer. Adv. Exp. Med. Biol. 2014;816:183–196. doi: 10.1007/978-3-0348-0837-8_8. PubMed DOI

Nabavizadeh R., Bobrek K., Master V.A. Risk stratification for bladder cancer: Biomarkers of inflammation and immune activation. Urol. Oncol. Semin. Orig. Investig. 2020;38:706–712. doi: 10.1016/j.urolonc.2020.04.006. PubMed DOI

Cancer-Related Inflammation|Nature. [(accessed on 10 December 2022)]. Available online: https://www-nature-com.ez.srv.pmu.ac.at/articles/nature07205.

Bhindi B., Hermanns T., Wei Y., Yu J., O Richard P., Wettstein M.S., Templeton A., Li K., Sridhar S.S., Jewett M.A.S., et al. Identification of the best complete blood count-based predictors for bladder cancer outcomes in patients undergoing radical cystectomy. Br. J. Cancer. 2016;114:207–212. doi: 10.1038/bjc.2015.432. PubMed DOI PMC

D’Andrea D., Moschini M., Gust K.M., Abufaraj M., Özsoy M., Mathieu R., Soria F., Briganti A., Rouprêt M., Karakiewicz P.I., 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. J. Surg. Oncol. 2017;115:455–461. doi: 10.1002/jso.24521. PubMed DOI

Morizawa Y., Miyake M., Shimada K., Hori S., Tatsumi Y., Nakai Y., Anai S., Tanaka N., Konishi N., Fujimoto K. Neutrophil-to-lymphocyte ratio as a detection marker of tumor recurrence in patients with muscle-invasive bladder cancer after radical cystectomy. Urol. Oncol. Semin. Orig. Investig. 2016;34:257.e11–257.e17. doi: 10.1016/j.urolonc.2016.02.012. PubMed DOI

Riva J.J., Malik K.M.P., Burnie S.J., Endicott A.R., Busse J.W. What is your research question? An introduction to the PICOT format for clinicians. J. Can. Chiropr. Assoc. 2012;56:167–171. PubMed PMC

Liberati M., Tetzlaff J., Altman D.G., PRISMA Group Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6:e1000097. doi: 10.1371/journal.pmed.1000100. PubMed DOI PMC

Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. PubMed DOI PMC

Sterne J.A.C., Hernán M.A., Reeves B.C., Savović J., Berkman N.D., Viswanathan M., Henry D., Altman D.G., Ansari M.T., Boutron I., et al. ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi: 10.1136/bmj.i4919. PubMed DOI PMC

Chang A., Cai J., Miranda G., Groshen S., Skinner D., Stein J.P. Usefulness of CA 125 as a preoperative prognostic marker for transitional cell carcinoma of the bladder. Pt 1J. Urol. 2004;172:2182–2186. doi: 10.1097/01.ju.0000143487.20280.ed. PubMed DOI

Kouba E.J., Lentz A., Wallen E.M., Pruthi R.S. Clinical use of serum CA-125 levels in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder. Urol. Oncol. Semin. Orig. Investig. 2009;27:486–490. doi: 10.1016/j.urolonc.2008.03.019. PubMed DOI

Hazzaa S.M., Elashry O.M., Afifi I.K. Clusterin as a Diagnostic and Prognostic Marker for Transitional Cell Carcinoma of the Bladder. Pathol. Oncol. Res. 2010;16:101–109. doi: 10.1007/s12253-009-9196-3. PubMed DOI

Rink M., Chun F.K., Dahlem R., Soave A., Minner S., Hansen J., Stoupiec M., Coith C., Kluth L.A., Ahyai S.A., et al. Prognostic Role and HER2 Expression of Circulating Tumor Cells in Peripheral Blood of Patients Prior to Radical Cystectomy: A Prospective Study. Eur. Urol. 2012;61:810–817. doi: 10.1016/j.eururo.2012.01.017. PubMed DOI

Ahmadi H., Djaladat H., Cai J., Miranda G., Daneshmand S. Precystectomy serum levels of carbohydrate antigen 19-9, carbohydrate antigen 125, and carcinoembryonic antigen: Prognostic value in invasive urothelial carcinoma of the bladder. Urol. Oncol. Semin. Orig. Investig. 2014;32:648–656. doi: 10.1016/j.urolonc.2014.01.019. PubMed DOI

Hermanns T., Bhindi B., Wei Y., Yu J., Noon A., O Richard P., Bhatt J.R., Almatar A., Jewett M.A.S., E Fleshner N., 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;111:444–451. doi: 10.1038/bjc.2014.305. PubMed DOI PMC

Viers B., Boorjian S.A., Frank I., Tarrell R.F., Thapa P., Karnes R.J., Thompson R.H., Tollefson M.K. Pretreatment Neutrophil-to-Lymphocyte Ratio Is Associated with Advanced Pathologic Tumor Stage and Increased Cancer-specific Mortality Among Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy. Eur. Urol. 2014;66:1157–1164. doi: 10.1016/j.eururo.2014.02.042. PubMed DOI

Djaladat H., Bruins H.M., Miranda G., Cai J., Skinner E.C., Daneshmand S. The association of preoperative serum albumin level and American Society of Anesthesiologists (ASA) score on early complications and survival of patients undergoing radical cystectomy for urothelial bladder cancer. BJU Int. 2014;113:887–893. doi: 10.1111/bju.12240. PubMed DOI

Liu J., Dai Y., Zhou F., Long Z., Li Y., Liu B., Xie D., Tang J., Tan J., Yao K., et al. The prognostic role of preoperative serum albumin/globulin ratio in patients with bladder urothelial carcinoma undergoing radical cystectomy. Urol. Oncol. Semin. Orig. Investig. 2016;34:484.e1–484.e8. doi: 10.1016/j.urolonc.2016.05.024. PubMed DOI

Tan Y.G., Eu E., On W.L.K., Huang H.H. Pretreatment neutrophil-to-lymphocyte ratio predicts worse survival outcomes and advanced tumor staging in patients undergoing radical cystectomy for bladder cancer. Asian J. Urol. 2017;4:239–246. doi: 10.1016/j.ajur.2017.01.004. PubMed DOI PMC

Christensen E., Birkenkamp-Demtröder K., Sethi H., Shchegrova S., Salari R., Nordentoft I.K., Wu H.-T., Knudsen M., Lamy P., Lindskrog S.V., et al. Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma. J. Clin. Oncol. 2019;37:1547–1557. doi: 10.1200/JCO.18.02052. PubMed DOI

Yuk H.D., Jeong C.W., Kwak C., Kim H.H., Ku J.H. De Ritis Ratio (Aspartate Transaminase/Alanine Transaminase) as a Significant Prognostic Factor in Patients Undergoing Radical Cystectomy with Bladder Urothelial Carcinoma: A Propensity Score-Matched Study. Dis. Markers. 2019;2019:6702964. doi: 10.1155/2019/6702964. PubMed DOI PMC

Ninomiya S., Kawahara T., Miyoshi Y., Yao M., Uemura H. A retrospective study on the possible systematic inflammatory response markers to predict the prognosis of patients with bladder cancer undergoing radial cystectomy. Mol. Clin. Oncol. 2020;13:47. doi: 10.3892/mco.2020.2117. PubMed DOI PMC

Fallah J., Diaz-Montero C.M., Rayman P., Wei W., Finke J.H., Kim J.S., Pavicic P.G., Lamenza M., Dann P., Company D., et al. Myeloid-Derived Suppressor Cells in Nonmetastatic Urothelial Carcinoma of Bladder Is Associated with Pathologic Complete Response and Overall Survival. Clin. Genitourin. Cancer. 2020;18:500–508. doi: 10.1016/j.clgc.2020.03.004. PubMed DOI

Su S., Liu L., Sun C., Yang L., Nie Y., Chen Y., Zhang J., Li S. Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer. Urol. Oncol. Semin. Orig. Investig. 2020;38:852.e1–852.e9. doi: 10.1016/j.urolonc.2020.05.031. PubMed DOI

Dohn L., Thind P., Salling L., Lindberg H., Oersted S., Christensen I., Laerum O., Illemann M., von der Maase H., Høyer-Hansen G., et al. Circulating Forms of Urokinase-Type Plasminogen Activator Receptor in Plasma Can Predict Recurrence and Survival in Patients with Urothelial Carcinoma of the Bladder. Cancers. 2021;13:2377. doi: 10.3390/cancers13102377. PubMed DOI PMC

Schuettfort V.M., D’andrea D., Quhal F., Mostafaei H., Laukhtina E., Mori K., Motlagh R.S., Rink M., Abufaraj M., Karakiewicz P.I., et al. Impact of preoperative serum albumin-globulin ratio on disease outcome after radical cystectomy for urothelial carcinoma of the bladder. Urol. Oncol. Semin. Orig. Investig. 2021;39:235.e5–235.e14. doi: 10.1016/j.urolonc.2020.11.005. PubMed DOI

Li S., Lu S., Liu X., Chen X. Association between the Pretreatment Albumin-to-Alkaline Phosphatase Ratio and Clinical Outcomes in Patients With Bladder Cancer Treated With Radical Cystectomy: A Retrospective Cohort Study. Front. Oncol. 2021;11:664392. doi: 10.3389/fonc.2021.664392. PubMed DOI PMC

Mari A., Muto G., Di Maida F., Tellini R., Bossa R., Bisegna C., Campi R., Cocci A., Viola L., Grosso A., et al. Oncological impact of inflammatory biomarkers in elderly patients treated with radical cystectomy for urothelial bladder cancer. Arab. J. Urol. 2021;19:2–8. doi: 10.1080/2090598X.2020.1814974. PubMed DOI PMC

Schuettfort V.M., Pradere B., D’Andrea D., Grossmann N.C., Quhal F., Mostafaei H., Laukhtina E., Mori K., Rink M., Karakiewicz P.I., et al. Prognostic Impact of Preoperative Plasma Levels of Urokinase Plasminogen Activator Proteins on Disease Outcomes after Radical Cystectomy. J. Urol. 2021;206:1122–1131. doi: 10.1097/JU.0000000000001936. PubMed DOI

Schuettfort V.M., D’Andrea D., Quhal F., Mostafaei H., Laukhtina E., Mori K., König F., Rink M., Abufaraj M., Karakiewicz P.I., et al. A panel of systemic inflammatory response biomarkers for outcome prediction in patients treated with radical cystectomy for urothelial carcinoma. BJU Int. 2022;129:182–193. doi: 10.1111/bju.15379. PubMed DOI PMC

Grossmann N.C., Schuettfort V.M., Pradere B., Rajwa P., Quhal F., Mostafaei H., Laukhtina E., Mori K., Motlagh R.S., Aydh A., et al. Impact of preoperative systemic immune-inflammation Index on oncologic outcomes in bladder cancer patients treated with radical cystectomy. Urol. Oncol. Semin. Orig. Investig. 2022;40:106.e11–106.e19. doi: 10.1016/j.urolonc.2021.10.006. PubMed DOI

Laukhtina E., Schuettfort V.M., D’andrea D., Pradere B., Mori K., Quhal F., Motlagh R.S., Mostafaei H., Katayama S., Grossmann N., et al. Preoperative plasma level of endoglin as a predictor for disease outcomes after radical cystectomy for nonmetastatic urothelial carcinoma of the bladder. Mol. Carcinog. 2022;61:5–18. doi: 10.1002/mc.23355. PubMed DOI PMC

Motlagh R.S., Schuettfort V.M., Mori K., Katayama S., Rajwa P., Aydh A., Grossmann N.C., Laukhtina E., Pradere B., Mostafai H., et al. Prognostic impact of insulin-like growth factor-I and its binding proteins, insulin-like growth factor-I binding protein-2 and -3, on adverse histopathological features and survival outcomes after radical cystectomy. Int. J. Urol. 2022;29:676–683. doi: 10.1111/iju.14869. PubMed DOI PMC

Mori K., Schuettfort V.M., Katayama S., Laukhtina E., Pradere B., Quhal F., Motlagh R.S., Mostafaei H., Grossmann N.C., Rajwa P., et al. Prognostic Role of Preoperative Vascular Cell Adhesion Molecule-1 Plasma Levels in Urothelial Carcinoma of the Bladder Treated With Radical Cystectomy. Ann. Surg. Oncol. 2022;29:5307–5316. doi: 10.1245/s10434-022-11575-4. PubMed DOI PMC

Lei Y., Jiao D., Yao Z., Wang L., Zhao Z. Prognostic values of preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte- to-monocyte ratio for patients with muscle- invasive bladder cancer undergoing radical cystectomy. Arch. Esp. Urol. 2022;75:287–294. PubMed

Schuettfort V.M., Pradere B., Trinh Q.-D., D’Andrea D., Quhal F., Mostafaei H., Laukhtina E., Mori K., Motlagh R.S., Rink M., et al. Impact of preoperative plasma levels of interleukin 6 and interleukin 6 soluble receptor on disease outcomes after radical cystectomy for bladder cancer. Cancer Immunol. Immunother. 2022;71:85–95. doi: 10.1007/s00262-021-02953-0. PubMed DOI PMC

Urabe F., Matsuzaki J., Ito K., Takamori H., Tsuzuki S., Miki J., Kimura T., Egawa S., Nakamura E., Matsui Y., et al. Serum microRNA as liquid biopsy biomarker for the prediction of oncological outcomes in patients with bladder cancer. Int. J. Urol. 2022;29:968–976. doi: 10.1111/iju.14858. PubMed DOI

Katayama S., Schuettfort V.M., Pradere B., Mori K., Mostafaei H., Quhal F., Motlagh R.S., Laukhtina E., Grossmann N.C., Aydh A., et al. Prognostic value of hepatocyte growth factor for muscle-invasive bladder cancer. J. Cancer Res. Clin. Oncol. 2022;148:3091–3102. doi: 10.1007/s00432-021-03887-x. PubMed DOI PMC

Inflammation and Cancer: Back to Virchow?-ScienceDirect. [(accessed on 11 December 2022)]. Available online: https://www-sciencedirect-com.ez.srv.pmu.ac.at/science/article/pii/S0140673600040460?via%3Dihub?ezproxy=true.

Fernandes J.V., Cobucci R., Jatobá C.A.N., Fernandes T., De Azevedo J.W.V., De Araújo J.M.G. The Role of the Mediators of Inflammation in Cancer Development. Pathol. Oncol. Res. POR. 2015;21:527–534. doi: 10.1007/s12253-015-9913-z. PubMed DOI

Seah J.-A., Leibowitz-Amit R., Atenafu E.G., Alimohamed N., Knox J.J., Joshua A.M., Sridhar S.S. Neutrophil-Lymphocyte Ratio and Pathological Response to Neoadjuvant Chemotherapy in Patients with Muscle-Invasive Bladder Cancer. Clin. Genitourin. Cancer. 2015;13:e229–e233. doi: 10.1016/j.clgc.2015.02.001. PubMed DOI

Song M., Graubard B.I., Rabkin C.S., Engels E.A. Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Sci. Rep. 2021;11:464. doi: 10.1038/s41598-020-79431-7. PubMed DOI PMC

Guthrie G.J.K., Charles K.A., Roxburgh C.S.D., Horgan P.G., McMillan D.C., Clarke S.J. The systemic inflammation-based neutrophil–lymphocyte ratio: Experience in patients with cancer. Crit. Rev. Oncol. Hematol. 2013;88:218–230. doi: 10.1016/j.critrevonc.2013.03.010. PubMed DOI

Lowsby R., Gomes C., Jarman I., Lisboa P., Nee P.A., Vardhan M., Eckersley T., Saleh R., Mills H. Neutrophil to lymphocyte count ratio as an early indicator of blood stream infection in the emergency department. Emerg. Med. J. 2015;32:531–534. doi: 10.1136/emermed-2014-204071. PubMed DOI

Adamstein N.H., MacFadyen J.G., Rose L.M., Glynn R.J., Dey A.K., Libby P., Tabas I.A., Mehta N.N., Ridker P.M. The neutrophil–lymphocyte ratio and incident atherosclerotic events: Analyses from five contemporary randomized trials. Eur. Heart J. 2021;42:896–903. doi: 10.1093/eurheartj/ehaa1034. PubMed DOI PMC

Park J.M. Neutrophil-to-lymphocyte ratio in trauma patients. J. Trauma Acute Care Surg. 2017;82:225–226. doi: 10.1097/TA.0000000000001266. PubMed DOI

Li W., Hou M., Ding Z., Liu X., Shao Y., Li X. Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Stroke: A Systematic Review and Meta-Analysis. Front. Neurol. 2021;12:686983. doi: 10.3389/fneur.2021.686983. PubMed DOI PMC

Lee M.-J., Park S.-D., Kwon S.W., Woo S.-I., Lee M.-D., Shin S.-H., Kim D.-H., Kwan J., Park K.-S. Relation between Neutrophil-to-Lymphocyte Ratio and Index of Microcirculatory Resistance in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Am. J. Cardiol. 2016;118:1323–1328. doi: 10.1016/j.amjcard.2016.07.072. PubMed DOI

Karakonstantis S., Kalemaki D., Tzagkarakis E., Lydakis C. Pitfalls in studies of eosinopenia and neutrophil-to-lymphocyte count ratio. Infect. Dis. 2018;50:163–174. doi: 10.1080/23744235.2017.1388537. PubMed DOI

Fest J., Ruiter R., Ikram M.A., Voortman T., van Eijck C.H.J., Stricker B.H. Reference values for white blood-cell-based inflammatory markers in the Rotterdam Study: A population-based prospective cohort study. Sci. Rep. 2018;8:10566. doi: 10.1038/s41598-018-28646-w. PubMed DOI PMC