IMR Press / FBE / Volume 15 / Issue 3 / DOI: 10.31083/j.fbe1503020
Open Access Original Research
Integrating Red Blood Cell Features and Hemoglobin Levels in Metastatic Renal Cell Carcinoma Patients Treated with Pazopanib or Cabozantinib: An Easily Exploitable Prognostic Score
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1 Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy
2 Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
3 Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), 43126 Parma, Italy
4 Oncology Unit, Macerata Hospital, 62100 Macerata, Italy
5 Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori'', 47014 Meldola, Italy
6 Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16122 Genova, Italy
7 Department of Medical Oncology, Santa Chiara Hospital, 38100 Trento, Italy
8 Division of Oncology, University Hospital “Maggiore della Carità", 28100 Novara, Italy
9 Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
10 Department of Medical Oncology, Fondazione Policlinico Campus Bio-Medico, 00161 Roma, Italy
11 Department of Health Sciences, University of Florence, 50139 Florence, Italy
12 Pathology Unit, University Hospital of Parma, 43126 Parma, Italy
13 Candiolo Cancer Institute, FPO-IRCCS, 10123 Turin, Italy
14 Medical Oncology Unit, Ospedale San Paolo, 17012 Savona, Italy
15 Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genova, 16166 Genova, Italy
16 Department of Oncology, Portsmouth Hospitals University NHS Trust, PO6 3LY Cosham, Portsmouth, UK
*Correspondence: (Sebastiano Buti)
These authors contributed equally.
Front. Biosci. (Elite Ed) 2023, 15(3), 20;
Submitted: 23 December 2022 | Revised: 28 May 2023 | Accepted: 2 June 2023 | Published: 28 July 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs. The primary endpoint was to correlate Hb, MCV, and RDW with progression-free survival (PFS) and overall survival (OS). Materials and Methods: Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed. Results: We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb 12 g/dL, MCV >87 fL, and RDW 16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS (p < 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2–3 versus 0–1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 vs 7.9 months; median OS (mOS): 33.7 vs 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39–0.75; p < 0.001, respectively), while the impact on PFS resulted in borderline significance. Conclusions: Our analyses demonstrate the prognostic role of a multiparametric score based on easily exploitable blood parameters, such as Hb concentration, MCV, and RDW. The red blood cell-based score may underlie the upregulation of the HIF-1α pathway and VEGF axis, thereby identifying a selected population who is likely to benefit from TKI therapy.

metastatic renal cell carcinoma (mRCC)
tyrosine-kinase inhibitors
prognostic score
Graphical Abstract
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Fig. 1.
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