Sarcomatoid Dedifferentiation in Metastatic Clear Cell Renal Cell Carcinoma and Outcome on Treatment With Anti–Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: A Retrospective Analysis

IntroductionThis study aimed to assess the efficacy of anti–vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKIs) in patients with metastatic clear cell renal cell carcinoma (m-ccRCC) with sarcomatoid dedifferentiation.Patients and MethodsThe files of all patients with m-ccRCC consecutively treated with first-line anti-VEGFR-TKIs at the authors' institution were retrospectively reviewed. Pathology slides from nephrectomy and metastasectomy were assessed for the presence and extent of sarcomatoid dedifferentiation.ResultsA total of 124 patients were included; nephrectomy and metastasectomy specimens were available in 117 and 35 patients, respectively. Thirty percent of the primary nephrectomy specimens had sarcomatoid features, and the median involvement of the sarcomatoid component was 21% (range, 1%-95%). Patients with an important sarcomatoid component, defined as ≥ 25% involvement of the tumor, had a very poor outcome: progression-free survival (PFS) and overall survival (OS) were 3 and 6 months, respectively, and no partial responses (PR) were observed. Patients without sarcomatoid dedifferentiation or with sarcomatoid involvement < 25% had a PFS of 12 months (P < .0001; hazard ratio [HR], 51; 95% CI, 12.58-207.3), an OS of 22 months (P < .0001, HR, 10.72; 95% CI, 3.56-32.25), and a PR rate of 50% (P = .0015). Patients with a sarcomatoid component ≥ 25% in the metastasectomy also had a poorer PFS and OS on anti-VEGFR-TKIs compared with patients with < 25% of sarcomatoid features at these sites.ConclusionPatients with m-ccRCC whose tumors contain a component of sarcomatoid dedifferentiation of ≥ 25% of the total tumor volume have a very poor outcome when treated with anti-VEGFR-TKIs. Analysis of the extent of sarcomatoid features in resected metastases can provide additional prognostic information.