The Systemic Immune-Inflammation Index (SII) Increases the Prognostic Significance of Lymphovascular Invasion in Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy

Hau-Chern Jan,1,2 Kuan-Yu Wu,1 Ta-Yao Tai,1 Han-Yu Weng,1 Wen-Horng Yang,1,3 Chien-Hui Ou,1,3 Che-Yuan Hu1,4 1Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan; 2Division of Urology, Department of Surgery, National Cheng Kung University Hospital Dou-Liou Branch, Yunlin, 640, Taiwan; 3Department of Urology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 4Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 701, TaiwanCorrespondence: Che-Yuan Hu; Chien-Hui Ou, Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Sheng-Li Road, Tainan, 70403, Taiwan, Tel +886-6-235-3535, Fax +886-6-238-3678, Email greatoldhu@gmail.com; donou1969@yahoo.com.twPurpose: Lymphovascular invasion (LVI) and systemic immune-inflammation index (SII) both have been proved to correlate with oncologic outcomes in upper tract urothelial carcinoma (UTUC). We hypothesize that integrating SII with LVI may be an aid for risk-stratification of prognosis. This study aimed to evaluate the prognostic significance of combined SII and LVI in patients with localized UTUC.Patients and Methods: A retrospective analysis of clinicopathological data of 554 UTUC patients who underwent radical nephroureterectomy (RNU) was conducted. The SII was calculated using the equation (preoperative serum neutrophil&ast;platelet/lymphocyte). Use of Kaplan–Meier analyses and Cox proportional hazards models were to evaluate associations of combining SII and LVI with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Furthermore, receiver operating characteristic (ROC) analysis was applied to estimate predictive ability of combining SII and LVI for oncological outcomes.Results: Positive LVI was significantly associated with advanced stage, high grade, necrosis, lymph node metastasis, and high-level SII. Positive LVI and high-level SII co-existence was significantly associated with unfavorable OS, CSS, and PFS in Kaplan-Meier analyses (all p < 0.001) and was an independent indicator of OS, CSS, and PFS (HR [95% CI]: 3.918 [2.168– 7.078], 5.623 [2.679– 11.801], 3.377 [2.138– 5.334]), respectively) in multivariate analyses. Furthermore, adding LVI and SII to a model that included standard pathologic predictors exhibited a better ability to predict survival in ROC analysis.Conclusion: The integration of SII and LVI was demonstrated to be a potential factor of poor outcomes in patients with localized UTUC. Notably, the combined use of LVI and SII can be a feasible and complementary factor to TNM staging in the prognostic assessment of UTUC patients in clinical practice. The validity of combination of the two markers would be considered in future prospective studies to evaluate its usefulness in staging and application of post-operative chemo or immunotherapy.Keywords: upper tract urothelial carcinoma, lymphovascular invasion, systemic immune-inflammation index, survival