{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:01:40Z","timestamp":1791928900341,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Given the increasing interest in the predictive role of inflammation in oncology, we aimed to assess the association between inflammatory factors (IFs) and the histopathological characteristics of bladder cancer (BC). Our objective was to correlate some of these IFs with BC progression and recurrence, identifying possible new diagnostic tools. Methods: We retrospectively analyzed 285 patients (79.8% male, 20.4% female; median age 73) who underwent transurethral resection of the bladder (TURB) between January 2016 and January 2022. The preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), systemic inflammation response index (SIRI), and standard clinical variables were collected one month before TURB and evaluated as predictors of recurrence and progression. Patients were stratified using the Youden Index and ROC analysis. Cox regression models were applied to identify independent predictors. Results: High-grade tumors were present in 74.6% of cases, and 34% were recurrent. Carcinoma in situ was found in 5%. After 72 months, 53% underwent radical cystectomy, and 13.7% died within 5 years. The optimal cutoffs were PLR 139, SIRI 1.12, PIV 248.49, NLR 2, SII 327. Smoking, primary MIBC, age, and lymph node status were significantly associated with recurrence. Elevated PLR correlated with recurrence and T2 progression (p = 0.004). Higher SIRI, PIV, and PLR levels were significantly associated with lymphovascular invasion and nodal metastasis (p &lt; 0.05). PLR was linked to recurrence in tumors \u2265 3 cm post-BCG (p = 0.004); high SIRI predicted recurrence within 48 months (p = 0.05). Conclusions: High PLR and SIRI levels were associated with recurrence. Our findings support the emerging role of IFs in predicting BC outcomes and suggest their potential inclusion in future prognostic models.<\/jats:p>","DOI":"10.3390\/cancers17132189","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T06:18:36Z","timestamp":1751264316000},"page":"2189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Prognostic Value of PLR, SIRI, PIV, SII, and NLR in Non-Muscle Invasive Bladder Cancer: Can Inflammatory Factors Influence Pathogenesis and Outcomes?"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2119-9023","authenticated-orcid":false,"given":"Francesco Pio","family":"Bizzarri","sequence":"first","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"},{"name":"Department of Urology, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-1214","authenticated-orcid":false,"given":"Marco","family":"Campetella","sequence":"additional","affiliation":[{"name":"Department of Urology, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"},{"name":"Department of Life Science, Health, and Health Professions, University Unilink, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3861-3545","authenticated-orcid":false,"given":"Giuseppe","family":"Palermo","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Koosha","family":"Moosavi","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Urology, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cret\u00ec","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9994-4316","authenticated-orcid":false,"given":"Filippo","family":"Gavi","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Panio","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Presutti","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Bellavia","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1919-8729","authenticated-orcid":false,"given":"Mauro","family":"Ragonese","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ciccarese","sequence":"additional","affiliation":[{"name":"Department of Oncology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-2117","authenticated-orcid":false,"given":"Roberto","family":"Iacovelli","sequence":"additional","affiliation":[{"name":"Department of Oncology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Sighinolfi","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-8479","authenticated-orcid":false,"given":"Marco","family":"Racioppi","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Sacco","sequence":"additional","affiliation":[{"name":"Department of Urology, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo","family":"Rocco","sequence":"additional","affiliation":[{"name":"Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Russo, P., Bizzarri, F.P., Filomena, G.B., Marino, F., Iacovelli, R., Ciccarese, C., Boccuto, L., Ragonese, M., Gavi, F., and Rossi, F. (2024). Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives. Cancers, 16.","DOI":"10.3390\/cancers16223766"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.euo.2022.05.005","article-title":"Intermediate-risk Non\u2013muscle-invasive Bladder Cancer: Updated Consensus Definition and Management Recommendations from the International Bladder Cancer Group","volume":"5","author":"Tan","year":"2022","journal-title":"Eur. Urol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.euo.2019.09.003","article-title":"What Is the Prognostic and Clinical Importance of Urothelial and Nonurothelial Histological Variants of Bladder Cancer in Predicting Oncological Outcomes in Patients with Muscle-invasive and Metastatic Bladder Cancer? A European Association of Urology Muscle Invasive and Metastatic Bladder Cancer Guidelines Panel Systematic Review","volume":"2","author":"Espinos","year":"2019","journal-title":"Eur. Urol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.mayocp.2017.07.010","article-title":"Management of Muscle-Invasive Urothelial Cancer and the Emerging Role of Immunotherapy in Advanced Urothelial Cancer","volume":"92","author":"Giridhar","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.eururo.2021.08.010","article-title":"European Association of Urology Guidelines on Non\u2013muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ)","volume":"81","author":"Babjuk","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s12094-018-1999-9","article-title":"Pretreatment neutrophil\/lymphocyte, platelet\/lymphocyte, lymphocyte\/monocyte, and neutrophil\/monocyte ratios and outcome in elderly breast cancer patients","volume":"21","author":"Losada","year":"2019","journal-title":"Clin. Transl. Oncol."},{"key":"ref_8","first-page":"264","article-title":"Are Markers of Systemic Inflammation Good Prognostic Indicators in Colorectal Cancer?","volume":"16","author":"Rossi","year":"2017","journal-title":"Clin. Color. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00268-017-4146-9","article-title":"Comparison of Prognostic Abilities Among Preoperative Laboratory Data Indices in Patients with Resectable Gastric and Esophagogastric Junction Adenocarcinoma","volume":"42","author":"Urabe","year":"2018","journal-title":"World J. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3712","DOI":"10.7150\/ijms.64658","article-title":"Preoperative neutrophil-to-lymphocyte, platelet-to-lymphocyte and monocyte-to-lymphocyte ratio as a prognostic factor in non-endometrioid endometrial cancer","volume":"18","author":"Song","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Russo, P., Palermo, G., Iacovelli, R., Ragonese, M., Ciccarese, C., Maioriello, G., Fantasia, F., Bizzarri, F.P., Marino, F., and Moosavi, K. (2024). Comparison of PIV and Other Immune Inflammation Markers of Oncological and Survival Outcomes in Patients Undergoing Radical Cystectomy. Cancers, 16.","DOI":"10.20944\/preprints202401.0298.v1"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Russo, P., Marino, F., Rossi, F., Bizzarri, F.P., Ragonese, M., Dibitetto, F., Filomena, G.B., Marafon, D.P., Ciccarese, C., and Iacovelli, R. (2023). Is Systemic Immune-Inflammation Index a Real Non-Invasive Biomarker to Predict Oncological Outcomes in Patients Eligible for Radical Cystectomy?. Medicina, 59.","DOI":"10.3390\/medicina59122063"},{"key":"ref_13","first-page":"393.e1","article-title":"SIRI as a biomarker for bladder neoplasm: Utilizing decision curve analysis to evaluate clinical net benefit","volume":"43","author":"Russo","year":"2025","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1177\/0391560321993584","article-title":"The prognostic importance of neutrophil-to-lymphocyte ratio in testicular cancer","volume":"88","author":"Merder","year":"2021","journal-title":"Urol. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.hemonc.2021.08.003","article-title":"Predicting if lung cancer will relapse\u2014The role of neutrophil\/lymphocyte ratio","volume":"16","author":"Chan","year":"2021","journal-title":"Hematol. Stem Cell Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1159\/000489152","article-title":"Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: A Pooled Analysis of Comparative Studies","volume":"46","author":"Wu","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/cncr.30422","article-title":"Neutrophil-to-lymphocyte ratio as a bladder cancer biomarker: Assessing prognostic and predictive value in SWOG 8710","volume":"123","author":"Ojerholm","year":"2017","journal-title":"Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.eururo.2025.02.019","article-title":"European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2025 Guidelines","volume":"87","author":"Bruins","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/bmj.39335.541782.AD","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"335","author":"Altman","year":"2007","journal-title":"BMJ"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1158\/0008-5472.CAN-15-0125","article-title":"Definition of Prostaglandin E2\u2013EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth","volume":"75","author":"Ma","year":"2015","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.oraloncology.2013.12.009","article-title":"The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma","volume":"50","author":"Clatot","year":"2014","journal-title":"Oral Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.juro.2008.03.024","article-title":"Radical Cystectomy for Carcinoma of the Bladder: 2,720 Consecutive Cases 5 Years Later","volume":"180","author":"Ghoneim","year":"2008","journal-title":"J. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Caini, S., Del Riccio, M., Vettori, V., Francolini, G., D\u2019ecclesiis, O., Cai, T., Gaeta, A., Bonaccorsi, G., Zanna, I., and Palli, D. (2022). Prognostic Impact of Post-Diagnosis Smoking Cessation among Bladder Cancer Patients: A Systematic Literature Review and Meta-Analysis. Cancers, 14.","DOI":"10.3390\/cancers14164022"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"467","DOI":"10.56434\/j.arch.esp.urol.20227505.68","article-title":"The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer","volume":"75","author":"Chen","year":"2022","journal-title":"Arch. Espanoles Urol."},{"key":"ref_26","first-page":"256.e1","article-title":"The systemic inflammation response index: An independent predictive factor for survival outcomes of bladder cancer stronger than other inflammatory markers","volume":"41","author":"Yilmaz","year":"2023","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.3390\/curroncol30030197","article-title":"Predictive Value of Inflammatory and Nutritional Indexes in the Pathology of Bladder Cancer Patients Treated with Radical Cystectomy","volume":"30","author":"Prijovic","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3892\/mco.2021.2264","article-title":"Preoperative risk stratification using plasma fibrinogen levels can predict lymphovascular invasion and poor prognosis in patients with upper urinary tract urothelial carcinoma","volume":"14","author":"Kuroda","year":"2021","journal-title":"Mol. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102144","DOI":"10.1016\/j.clgc.2024.102144","article-title":"Prognostic Value of NLR, PLR, SII, and dNLR in Urothelial Bladder Cancer Following Radical Cystectomy","volume":"22","author":"Salari","year":"2024","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7131","DOI":"10.2147\/JIR.S345790","article-title":"Systemic Immune-Inflammatory Index as a Predictor of Lymph Node Metastasis in Endometrial Cancer","volume":"14","author":"Lei","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e30380","DOI":"10.1097\/MD.0000000000030380","article-title":"Prognostic significance of systemic immune-inflammation index in patients with bladder cancer: A systematic review and meta-analysis","volume":"101","author":"Cao","year":"2022","journal-title":"Medicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4111\/kju.2010.51.3.165","article-title":"The Efficacy of the EORTC Scoring System and Risk Tables for the Prediction of Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer after Intravesical Bacillus Calmette-Guerin Instillation","volume":"51","author":"Seo","year":"2010","journal-title":"Korean J. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.euo.2021.05.006","article-title":"Deep Learning-based Recalibration of the CUETO and EORTC Prediction Tools for Recurrence and Progression of Non\u2013muscle-invasive Bladder Cancer","volume":"5","author":"Jobczyk","year":"2022","journal-title":"Eur. Urol. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S1470-2045(23)00061-X","article-title":"Artificial intelligence-based model for lymph node metastases detection on whole slide images in bladder cancer: A retrospective, multicentre, diagnostic study","volume":"24","author":"Wu","year":"2023","journal-title":"Lancet Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/13\/2189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:50Z","timestamp":1760032850000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/13\/2189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,28]]},"references-count":34,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cancers17132189"],"URL":"https:\/\/doi.org\/10.3390\/cancers17132189","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,28]]}}}