PURPOSE: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). RESULTS: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis. CONCLUSIONS: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of Medical and Surgical Specialties Radiological Science and Public Health Urology Unit ASST Spedali Civili of Brescia University of Brescia Brescia Italy

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology CHRU Tours Université François Rabelais de Tours PRES Centre Val de Loire Tours France

Department of Urology Dentistry and Pharmaceutical Sciences Okayama University Graduate School of Medicine Okayama Japan

Department of Urology Ehime University Graduate School of Medicine Ehime Japan

Department of Urology IRCCS European Institute of Oncology Milan Italy

Department of Urology Medical University of Vienna Währinger Gürtel 18 20 1090 Vienna Austria

Department of Urology Shariati Hospital Tehran University of Medical Sciences Tehran Iran

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Naples Federico 2 Naples Italy

Department of Urology University of Texas Southwestern Medical Center Dallas TX USA

Department of Urology Vita Salute San Raffaele University Milan Italy

Department of Urology Weill Cornell Medical College New York NY USA

European Association of Urology Research Foundation Arnhem Netherlands

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

Research Division of Urology Department of Special Surgery The University of Jordan Amman Jordan

Urology department Sorbonne Université ONCOTYPE URO AP HP Hôpital Pitié Salpêtrière GRC n°5 75013 Paris France

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