OBJECTIVES: Insulin-like growth factor-I and its binding proteins are involved in cancer development, progression, and metastasis. In urothelial carcinoma, the impact of this pathway is still poorly investigated. The present large cohort study aimed to evaluate the association of preoperative circulating levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 on outcomes after radical cystectomy. METHODS: A retrospective cohort study of the plasma specimens from 1036 consecutive urothelial carcinoma patients who were treated with radical cystectomy. The primary and secondary outcomes were adverse histopathological features and survival outcomes. Binominal logistic regression and multivariable Cox regression analyses were performed to assess the association of plasma levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 with outcomes. RESULTS: On multivariable analysis adjusting for the effects of preoperative variables, lower insulin-like growth factor-I binding protein-2 levels were associated with an increased risk of lymph node metastasis and (any non-organ confined disease) any non-organ confined disease. Insulin-like growth factor-I binding protein-3 levels were also inversely independently associated with lymph node metastasis. Receiver operating characteristic curve analysis showed that the addition of insulin-like growth factor-I binding proteins biomarkers to a reference model significantly improved the discriminating ability for the prediction of lymph node metastasis (+10.0%, P < 0.001). On multivariable Cox regression models, lower levels of both insulin-like growth factor-I binding protein-2 and -3 plasma levels were associated with recurrence-free survival, cancer-specific survival, and overall survival. insulin-like growth factor-I binding protein-2 and -3 levels and improved the discrimination of a standard reference model for the prediction of recurrence-free survival, cancer-specific survival, and overall survival (+4.9%, 4.9%, 2.3%, respectively). CONCLUSIONS: Preoperative insulin-like growth factor-I binding protein-2 and -3 are significantly associated with features of biologically and clinically aggressive urothelial carcinoma. These biomarkers improved prognostic urothelial carcinoma models.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Center Montreal Quebec Canada

Department of Pathology Medical University of Vienna Vienna Austria

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

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 King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology King Faisal Medical City Abha Saudi Arabia

Department of Urology Medical University of Silesia Zabrze Poland

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

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Hospital Zurich Zurich Switzerland

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

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

Department of Urology Weill Cornell Medical College New York New York USA

Division of Urology Molinette Hospital University of Torino School of Medicine Torino Italy

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Men's Health and Reproductive Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran

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

Unit of Urology Division of Oncology URI IRCCS Ospedale San Raffaele Milan Italy

Int J Urol. 2022 Jul;29(7):684. doi: 10.1111/iju.14902. PubMed

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Blood-Based Biomarkers as Prognostic Factors of Recurrent Disease after Radical Cystectomy: A Systematic Review and Meta-Analysis