BACKGROUND: Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC) worldwide. The systemic immune-inflammation index (SII) is a prognostic marker for several types of malignant neoplasms, including mRCC, in the era of tyrosine kinase inhibitor (TKI) treatment. Data regarding the prognostic value of the SII in patients with mRCC treated with immunotherapy are scarce and controversial. METHODS: We retrospectively collected the data of patients with mRCC from 56 centers in 18 countries. SII (Platelet × Neutrophil/Lymphocyte count) was calculated prior to the first systemic treatment and cut-off was defined by a survival receiver operating characteristic (ROC) analysis. The primary objective of our retrospective study was to assess the outcomes of patients treated with first-line immunotherapy. RESULTS: Data from 1034 mRCC patients was collected and included in this analysis. The SII cut-off value was 1265. After a follow-up of 26.7 months, and the overall survival (OS) and progression-free survival (PFS) were 39.8 and 15.7 months, respectively. According to SII (low vs. high), patients with low-SII had longer OS (55.7 vs. 22.2 months, P < .001), better PFS (20.8 vs. 8.5 months, P < .001), and higher overall response rate (52 vs. 37%, P = .033). CONCLUSION: A high SII is associated with poor oncological outcomes in patients with mRCC. SII could be an easily accessible prognostic indicator for use in clinical practice.

2nd Propaedeutic Department of Internal Medicine ATTIKON University Hospital National and Kapodistrian University of Athens School of Medicine Athens Greece

Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy

Department of Clinical Oncology and Radiotherapy University Hospital Hradec Kralove Hradec Kralove Czechia

Department of Medical Oncology Army Hospital Research and Referral New Delhi India

Department of Medical Oncology Centre Hospitalier de Jolimont Haine Saint Paul Belgium

Department of Medical Oncology MD Anderson Cancer Center Madrid Madrid Spain

Department of Medical Oncology University Hospital Ramón y Cajal Madrid Spain

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer University Hospital Prague Czech Republic

Department of Oncology and Radiotherapeutics Faculty of Medicine and University Hospital Charles University Pilsen Czech Republic; Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Uro oncology Maria Sklodowska Curie National Research Institute of Oncology Warsaw Warsaw Poland

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology University Hospital Bonn 53127 Bonn Germany

Hematology and Oncology Department Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico

Latin American Cooperative Oncology Group LACOG Porto Alegre RS Brazil; Hospital Sirio Libanês Brasilia DF Brazil; PUCRS School of Medicine Porto Alegre RS Brazil

Latin American Cooperative Oncology Group LACOG Porto Alegre RS Brazil; PUCRS School of Medicine Porto Alegre RS Brazil

Markey Cancer Center University of Kentucky Lexington KY

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Italia

Medical Oncology Tawam Hospital Al Ain United Arab Emirates

Oncology Unit Macerata Hospital Macerata Italy

Urologic Oncology Champalimaud Clinical Center Lisbon Portugal

References provided by Crossref.org

Real-World Primary Resistance to First-Line Immune-Based Combinations in Patients with Advanced Renal Cell Carcinoma (ARON-1)