BACKGROUND: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of Systemic Immune-Inflammation Index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN. METHODS: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut‑off value, we found 710 to have the maximum Youden Index value. The overall population was therefore divided into two SII groups using this cut‑off (low, <710 vs. high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's Concordance Index (C-Index). The clinical value of the SII was evaluated with decision curve analysis (DCA). RESULTS: Among 613 mRCC patients, 298 (49%) patients had a SII≥710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95% CI: 1.07-1.54, P=0.01) and CSS (HR: 1.29, 95% CI: 1.08-1.55, P=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥710 was associated with OS (HR: 1.25, 95% CI: 1.04-1.50, P=0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.52, P=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index: 0.637 vs. 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII≥710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95% CI: 1.02-1.67, P=0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95% CI: 1.04-1.61, P=0.02) and CSS (HR: 1.31, 95% CI: 1.05-1.63, P=0.02). CONCLUSIONS: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal QC Canada

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

Department of Urology and Division of Experimental Oncology Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology European Institute of Oncology IRCCS Milan Italy

Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology San Luigi Gonzaga Hospital University of Turin Turin Italy

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Hospital of Tours Tours France

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

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

Department of Urology Weill Cornell Medical College New York NY USA

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

European Association of Urology Research Foundation Arnhem the 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

Radiological Science and Public Health University of Brescia Brescia Italy

Research Center for Evidence Based Medicine Tabriz University of Medical Sciences Tabriz Iran

Urology Unit Department of Medical and Surgical Specialties ASST Spedali Civili of Brescia Brescia Italy

Minerva Urol Nephrol. 2022 Jun;74(3):372-375. doi: 10.23736/S2724-6051.22.04957-6. PubMed

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