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Introduction: Prompt diagnosis and differentiation between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) are essential in the treatment of bladder cancer. Inflammation-based biomarkers have recently emerged as potential tools for improving cancer diagnostics and prognostication. This study aims to evaluate the potential value of the Systemic Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), Pan-immune Inflammation Value (PIV), and Platelet-to-Lymphocyte Ratio (PLR) as predictors of muscle-invasive disease. Materials and methods: Analyzed data included 310 bladder tumors. The SII, SIRI, PIV, and PLR were calculated from pre-TURBT complete blood-count results. Differences in inflammatory markers between pathological stages (pTa–pT4) were examined using ANOVA with Tukey’s post hoc testing. Optimal cutoff values for distinguishing NMIBC from MIBC were identified using ROC curve analysis and Youden’s J statistic. Logistic regression models incorporating age, sex, the number of recurrences, and each inflammatory index were developed to evaluate their predictive performance in patients treated with curative intent. Results: All investigated inflammation indices significantly differed across tumor stages (p < 0.001), with lower values observed in pTa tumors compared with muscle-invasive disease. Determined cutoff values for muscle-invasive disease were 865.63 for SII, 2.02 for SIRI, 579.28 for PIV, and 166.35 for PLR. Logistic regression models demonstrated promising diagnostic performance, achieving AUC values of 0.812 (SII), 0.816 (SIRI), 0.821 (PIV), and 0.795 (PLR); sensitivity and specificity were 76% and 75% for SII, 79% and 77% for SIRI, 80% and 72% for PIV, and 88% and 59% for PLR. Discussion: The presented results indicate that inflammation-based indices vary meaningfully between bladder cancer stages and may be utilized in early identification of muscle-invasive disease. As inexpensive and widely available biomarkers, they offer potential value in the evaluation of suspected MIBC before the final pathology report and could enhance the diagnostic process. Full article