The role of mean corpuscular volume and red cell distribution width in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors: the MARECAP retrospective study

Abstract

Background: Tyrosine-kinase inhibitors (TKIs) and immunotherapy represent the backbone treatment for metastatic renal cell carcinoma (mRCC) patients. The aim of the present study was to describe mean corpuscular volume (MCV) and red cell distribution width (RDW) in mRCC patients treated with pazopanib or cabozantinib, and to explore their potential impact on oncological outcomes. Materials and methods: We conducted a multicenter retrospective observational study in mRCC patients treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Descriptive statistics, univariate, and multivariate analyses were performed. Objectives: The primary endpoints were the incidence and trend over time of anemia, macrocytosis (elevated MCV), and anisocytosis (elevated RDW). The secondary endpoints were the correlations of MCV and RDW with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: A total of 301 patients were enrolled; mean Hb value was 12.5 g/dl, a mean increase of 1 g/dl was observed at day 15 and maintained at 3 months. Most patients had baseline macrocytosis (MCV levels > 87 fl), with a significant mean increase after 3 months of treatment. At univariate analysis patients with macrocytosis had better ORR, longer PFS, and OS. About one third of patients had baseline anisocytosis (RDW > 16%), with a significant mean increase after 3 months of treatment. At univariate analysis, patients with RDW values ⩽ 16% had higher ORR, longer PFS, and OS. At multivariate analysis, baseline macrocytosis was significantly associated with better PFS in patients treated with pazopanib and baseline anisocytosis with shorter OS in all patients. Conclusions: mRCC patients treated with pazopanib or cabozantinib may have baseline macrocytosis and anisocytosis. A significant increase of Hb, MCV, and RDW after TKIs start was observed. Baseline macrocytosis is positively correlated with PFS in patients treated with pazopanib and baseline anisocytosis affects survival of patients treated with TKIs.

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

“…Other studies documented a correlation between RDW and the outcome of patients with mRCC as higher RDW at baseline, which re ects anisocytosis, has been associated with a poorer PFS and OS [14,31,32]. So, macrocytosis, lower degree of anisocytosis and higher level of Hb were found to be positive prognostic factors in patients treated with TKIs [14]. Accordingly, based on these observations we are planning a prospective study to understand the mechanistic basis underlying the changes in the red cell parameters during the treatment with TKIs.…”

“…[15][16][17]. Moreover, it has been consistently noted that TKI therapy is associated with MCV and RDW changes [14,18]. Macrocytosis at baseline and following TKI treatment has been correlated to a better survival outcome [14,[19][20][21][22].…”

“…Moreover, it has been consistently noted that TKI therapy is associated with MCV and RDW changes [14,18]. Macrocytosis at baseline and following TKI treatment has been correlated to a better survival outcome [14,[19][20][21][22]. Other studies documented a correlation between RDW and the outcome of patients with mRCC as higher RDW at baseline, which re ects anisocytosis, has been associated with a poorer PFS and OS [14,31,32].…”

“…Our previous study showed that a signi cant proportion of patients with mRCC undergoing TKIs (pazopanib or cabozantinib) exhibited an increased MCV and/or RDW at baseline. A higher MCV (macrocytosis) at baseline was associated with improved PFS in patients treated with pazopanib, while a higher RDW (anisocytosis) was linked to a poorer prognosis in all patients who received pazopanib or cabozantinib [14]. Hence, macrocytosis, lower degree of anisocytosis and higher level of Hb were found to be positive prognostic factors.…”

“…On the other hand, anaemia is a common condition in patients with mRCC and has a detrimental effect on survival, according to both the IMDC and Memorial Sloan Kettering Cancer Centre (MSKCC) score [7,13]. Anaemia is also one of the most common side effects of VEGFR-TKIs, although an increased hemoglobin (Hb) concentration and RBC count has also been noted after treatment with these agents [14][15][16][17]. Yet, TKIs could modify other RBC parameters such as mean corpuscular volume (MCV) and red cell distribution width (RDW), which re ects anisocytosis [14,[18][19][20][21][22].…”