Metastatic Chromophobe Renal Cell Carcinoma: Presence or Absence of Sarcomatoid Differentiation Determines Clinical Course and Treatment Outcomes.

Abstract

Sarcomatoid features (SF) in renal cell carcinoma (RCC) denote poor prognosis. Data for metastatic chromophobe RCC (ChRCC) with SF are limited. We studied clinical outcomes and genomic features in this setting. We performed a retrospective review of newly diagnosed metastatic ChRCC patients; end points included overall survival (OS), time to treatment failure (TTF), and time to metastatic recurrence (TTR) after nephrectomy for localized disease. A subset of patients underwent next-generation sequencing (NGS). Outcomes were compared using nonparametric tests. One hundred nine patients with metastatic ChRCC were identified including 29 with SF. Median TTR after nephrectomy was shorter for patients with versus without SF (2.7 months [95% confidence interval (CI), 0.7-6.9] versus 48.8 months [95% CI, 30.8-80.7], log rank P< .001). Median TTF during first-line therapy was shorter for patients with versus without SF (1.8 months [95% CI, 0.9-2.7] vs. 8.0 months [95% CI, 5.1-13.0]; log rank P< .001). No responses were observed in 6 patients treated with nivolumab including 4 with SF. Median OS was inferior for patients with versus without SF (38 months vs.7.5 months; hazard ratio, 4.7 [95% CI, 2.7-8.2]; P< .001). NGS, performed in 22 patients, showed that 64% and 45% harbored tumor protein P53 and phosphatase and tensin homolog alterations, respectively. Microsatellite instability high status was identified in 3 patients. Metastatic ChRCC patients with SF had worse outcomes compared with those without SF. Median TTR< 3 months for this subgroup supports close surveillance after nephrectomy for localized tumors. Lack of benefit with various systemic regimens warrants studying underlying biology and investigating novel agents.