Integrating Red Blood Cell Features and Hemoglobin Levels in Metastatic Renal Cell Carcinoma Patients Treated with Pazopanib or Cabozantinib: An Easily Exploitable Prognostic Score

Abstract

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.

External validation of a red cell-based blood prognostic score in patients with metastatic renal cell carcinoma treated with first-line immunotherapy combinations

“…Our previous study demonstrated the prognostic significance of the red cell-based score incorporating Hb, MCV, and RDW, in patients with mRCC undergoing TKI treatment. Patients carrying at least two favourable prognostic factors experienced notably extended PFS and OS compared to those with 0 to 1 positive prognostic factors [ 23 ]. In the present work, we aimed to validate the red cell-based score in a more actual clinical setting involving a population of patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI).…”

“…According to our previous study on patients with mRCC treated with TKIs, MCV > 87 fl (macrocytosis), RDW 16% (anisocytosis) and Hb ≥ 12 g/dL (absence of anaemia) were considered favourable prognostic factors. Based on the number of positive prognostic factors, we divided our patient population into two groups: favourable group (2–3 good factors) and unfavourable (0–1 good factors) [ 23 ].…”

“…Focusing on the same population, our group developed a red cell-based score through the integration of Hb, MCV and RDW, and delineated two prognostic groups: unfavourable group (0–1 good factors) and favourable group (2–3 good factors). Irrespective of other established prognostic factors, patients in the favourable group demonstrated significantly longer PFS and OS when compared to those in the unfavourable group [ 23 ]. In addition to the prognostic significance, these studies suggested that Hb, MCV and RDW may serve as an indirect indicators of the activation and alterations of the HIF-1α pathway among patients with mRCC undergoing TKIs [ 24 ].…”

External Validation of a Red Cell-based Blood Prognostic Score in Patients With Metastatic Renal Cell Carcinoma Treated With First- Line Immunotherapy Combinations

“…According to our previous study on patients with mRCC treated with TKIs, MCV > 87 (macrocytosis), RDW 16% (anisocytosis) and Hb ≥ 12 g/dL (absence of anaemia) were considered favourable prognostic factors. Based on the number of positive prognostic factors, we divided our patient population into two groups: favourable group (2-3 good factors) and unfavourable (0-1 good factors) [23].…”

“…Focusing on the same population, our group developed a red cell-based score through the integration of Hb, MCV and RDW, and delineated two prognostic groups: unfavourable group (0-1 good factors) and favourable group (2-3 good factors). Irrespective of other established prognostic factors, patients in the favourable group demonstrated signi cantly longer PFS and OS when compared to those in the unfavourable group [23]. In addition to the prognostic signi cance, these studies suggested that Hb, MCV and RDW may serve as an indirect indicators of the activation and alterations of the HIF-1α pathway among patients with mRCC undergoing TKIs [24].…”