Sarcomatoid features, necrosis, and grade are prognostic factors in metastatic clear cell renal cell carcinoma with vascular endothelial growth factor-targeted therapy.

Various clinical and laboratory parameters are used to determine the prognosis of patients with renal cell carcinoma (RCC), but the prognostic significance of histologic features has not been fully examined in patients with metastatic clear cell RCC receiving vascular endothelial growth factor (VEGF)/tyrosine kinase inhibitor (TKI; VEGF-TKI)-targeted therapy. To define prognostic clinicopathological factors, 83 such patients were retrospectively analyzed. Of these patients, 38 (45.8%) showed response to VEGF-TKI, whereas 45 (54.2%) were nonresponsive. Response to VEGF-TKI was associated with less than 10% sarcomatoid features and less than 10% tumor necrosis. Multivariate analysis showed that tumor necrosis was independently prognostic of VEGF-TKI response. During a median follow-up of 18 months (range, 1-62 months), 54 patients (65.1%) showed disease progression and 44 (53.0%) died. Shorter progression-free survival and overall survival (OS) were associated with a period less than 1 year from initial diagnosis to VEGF-TKI initiation, high Fuhrman grade, at least 10% sarcomatoid features, and at least 10% tumor necrosis. In addition, thrombocytosis was associated with shorter OS. Multivariate analysis showed that sarcomatoid features was independently prognostic of progression-free survival, whereas time from initial diagnosis to VEGF-TKI initiation and sarcomatoid features were independent prognostic factors of OS. In summary, sarcomatoid features, tumor necrosis, and tumor grade are histologic prognostic factors and should be considered in determining whether to initiate targeted treatment in patients with metastatic clear cell RCC.