Nico C Grossmann1, Victor M Schuettfort2, Benjamin Pradere3, Pawel Rajwa4, Fahad Quhal5, Hadi Mostafaei6, Ekaterina Laukhtina7, Keiichiro Mori8, Reza S Motlagh9, Abdulmajeed Aydh3, Satoshi Katayama10, Marco Moschini11, Christian D Fankhauser11, Thomas Hermanns12, Mohammad Abufaraj13, Dong-Ho Mun3, Kristin Zimmermann14, Harun Fajkovic15, Martin Haydter16, Shahrokh F Shariat17. 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Hospital Zurich, Zurich, Switzerland. 2. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 3. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 4. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland. 5. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia. 6. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 7. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 8. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 9. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Teheran, Iran. 10. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 11. Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland. 12. Department of Urology, University Hospital Zurich, Zurich, Switzerland. 13. Department of Special Surgery, Division of Urology, Jordan University Hospital, The University of Jordan, Amman, Jordan. 14. Department of Urology, Federal Armed Service Hospital Koblenz, Koblenz, Germany. 15. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Society, Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. 16. Department of Urology, Landesklinikum Wiener Neustadt, Vienna, Austria. 17. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Special Surgery, Division of Urology, Jordan University Hospital, The University of Jordan, Amman, Jordan; Karl Landsteiner Society, Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern, Dallas, TX. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Abstract
PURPOSE: To investigate the predictive and prognostic value of the preoperative systemic immune-inflammation index (SII) in patients undergoing radical cystectomy (RC) for clinically non-metastatic urothelial cancer of the bladder (UCB). METHODS: Overall, 4,335 patients were included, and the cohort was stratified in two groups according to SII using an optimal cut-off determined by the Youden index. Uni- and multivariable logistic and Cox regression analyses were performed, and the discriminatory ability by adding SII to a reference model based on available clinicopathologic variables was assessed by area under receiver operating characteristics curves (AUC) and concordance-indices. The additional clinical net-benefit was assessed using decision curve analysis (DCA). RESULTS: High SII was observed in 1879 (43%) patients. On multivariable preoperative logistic regression, high SII was associated with lymph node involvement (LNI; P = 0.004), pT3/4 disease (P <0.001), and non-organ confined disease (NOCD; P <0.001) with improvement of AUCs for predicting LNI (P = 0.01) and pT3/4 disease (P = 0.01). On multivariable Cox regression including preoperative available clinicopathologic values, high SII was associated with recurrence-free survival (P = 0.028), cancer-specific survival (P = 0.005), and overall survival (P = 0.006), without improvement of concordance-indices. On DCAs, the inclusion of SII did not meaningfully improve the net-benefit for clinical decision-making in all models. CONCLUSION: High preoperative SII is independently associated with pathologic features of aggressive disease and worse survival outcomes. However, it did not improve the discriminatory margin of a prediction model beyond established clinicopathologic features and failed to add clinical benefit for decision making. The implementation of SII as a part of a panel of biomarkers in future studies might improve decision-making.
PURPOSE: To investigate the predictive and prognostic value of the preoperative systemic immune-inflammation index (SII) in patients undergoing radical cystectomy (RC) for clinically non-metastatic urothelial cancer of the bladder (UCB). METHODS: Overall, 4,335 patients were included, and the cohort was stratified in two groups according to SII using an optimal cut-off determined by the Youden index. Uni- and multivariable logistic and Cox regression analyses were performed, and the discriminatory ability by adding SII to a reference model based on available clinicopathologic variables was assessed by area under receiver operating characteristics curves (AUC) and concordance-indices. The additional clinical net-benefit was assessed using decision curve analysis (DCA). RESULTS: High SII was observed in 1879 (43%) patients. On multivariable preoperative logistic regression, high SII was associated with lymph node involvement (LNI; P = 0.004), pT3/4 disease (P <0.001), and non-organ confined disease (NOCD; P <0.001) with improvement of AUCs for predicting LNI (P = 0.01) and pT3/4 disease (P = 0.01). On multivariable Cox regression including preoperative available clinicopathologic values, high SII was associated with recurrence-free survival (P = 0.028), cancer-specific survival (P = 0.005), and overall survival (P = 0.006), without improvement of concordance-indices. On DCAs, the inclusion of SII did not meaningfully improve the net-benefit for clinical decision-making in all models. CONCLUSION: High preoperative SII is independently associated with pathologic features of aggressive disease and worse survival outcomes. However, it did not improve the discriminatory margin of a prediction model beyond established clinicopathologic features and failed to add clinical benefit for decision making. The implementation of SII as a part of a panel of biomarkers in future studies might improve decision-making.