INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.

Departement of Urology Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montréal Health Center Montréal Québec Canada

Departement of Urology James Buchanan Brady Urological Institute Johns Hopkins University Baltimore MD

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

Department of Surgery S H Ho Urology Centre The Chinese University of Hong Kong Hong Kong SAR China

Department of Surgical Sciences Division of Urology Torino School of Medicine Turin Italy

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

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

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic; Department of Special Surgery Division of Urology The University of Jordan Amman Jordan; Department of Urology University of Texas Southwestern Medical Center Dallas TX; Departments of Urology Weill Cornell Medical College New York NY; Departement of Urology Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Department of Urology Research Center for Evidence Medicine Tabriz University of Medical Sciences Tabriz Iran

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Jikei University School of Medicine Tokyo Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Semmelweis University Budapest Hungary

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Shariati Hospital Tehran University of Medical Sciences Tehran Iran

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology Jagiellonian University Cracow Poland

Department of Urology Pitié Salpêtrière Hospital AP HP GRC 5 Predictive Onco Urology Sorbonne University Paris France

Department of Urology University of Texas Southwestern Medical Center Dallas TX

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