PURPOSE: We assessed the prognostic value of systemic immune-inflammation index (SII) to refine risk stratification of the heterogeneous spectrum of patients with non-muscle-invasive bladder cancer (NMIBC) METHODS: In this multi-institutional cohort, preoperative blood-based SII was retrospectively assessed in 1117 patients with NMIBC who underwent transurethral resection of bladder (TURB) between 1996 and 2007. The optimal cut-off value of SII was determined as 580 using the best Youden index. Cox regression analyses were performed. The concordance index (C-index) and decision curve analysis (DCA) were used to assess the discrimination of the predictive models. RESULTS: Overall, 309 (28%) patients had high SII. On multivariable analyses, high SII was significantly associated with worse PFS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.77; P = 0.003) and CSS (HR 2.53; 95% CI 1.42-4.48; P = 0.001). Subgroup analyses, according to the European Association of Urology guidelines, demonstrated the main prognostic impact of high SII, with regards to PFS (HR 3.39; 95%CI 1.57-7.31; P = 0.002) and CSS (HR 4.93; 95% CI 1.70-14.3; P = 0.005), in patients with intermediate-risk group; addition of SII to the standard predictive model improved its discrimination ability both on C-index (6% and 12%, respectively) and DCA. In exploratory intergroup analyses of patients with intermediate-risk, the improved discrimination ability was retained the prediction of PFS and CSS. CONCLUSION: Preoperative SII seems to identify NMIBC patients who have a worse disease and prognosis. Such easily available and cheap standard biomarkers may help refine the decision-making process regarding adjuvant treatment in patients with intermediate-risk NMIBC.

• Keywords
• Biomarker, Intermediate-risk, NMIBC, SII, Survival,
• MeSH
• Risk Assessment MeSH
• Neoplasm Invasiveness MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Bladder Neoplasms complications   immunology   pathology   MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Inflammation etiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

PURPOSE: The Plasminogen Activation System (PAS) plays a role in tumor growth, invasion and metastasis and has been associated with oncological outcomes in urinary bladder carcinoma (UBC). The use of the different components of this system as molecular markers could improve our understanding of the heterogeneous behavior of UBC and might enable earlier disease detection, individual risk stratification, more accurate outcome prediction and be a rationale for new targeted therapies. METHODS: A comprehensive literature search including relevant articles up to October 2020 was performed using the MEDLINE/PubMed database. RESULTS: The components of the PAS axis are involved in tumor progression through their signaling processes during angiogenesis, cell migration, metastasis and adhesion. The body of evidence shows an association of PAS component overexpression with adverse pathological features and clinical outcome in UBC. Overexpressed PAS components correlate with a higher pathological tumor grade and advanced tumor stage. In non-muscle-invasive bladder cancer (NMIBC), the PAS components were associated with disease outcome while in muscle-invasive bladder cancer (MIBC), it was associated with disease outcome and pathological features. Possible therapeutic approaches in the PAS for the treatment of UBC have only been sparsely investigated in in vitro and in vivo studies. Intravesical plasminogen activator inhibitor 1 (PAI-1) instillation in animal models yielded interesting results and warrant further exploration in Phase II studies. CONCLUSION: The overexpression of PAS components in UBC tumor tissue is associated with adverse pathological features and worse oncological outcomes. These findings are mainly based on preclinical studies and retrospective series, which requires further prospective studies to translate the PAS into clinically useful biomarkers and therapeutic targets.

• Keywords
• PAI, review, therapy, uPA, uPAR, urothelial cancer,
• Publication type
• Journal Article MeSH
• Review MeSH