Prognostic implications of sarcomatoid and rhabdoid differentiation in patients with grade 4 renal cell carcinoma

Objective: Sarcomatoid and rhabdoid differentiation are associated with poor outcomes in renal cell carcinoma (RCC). We examined the impact of differentiation on cancer-specific survival (CSS) in surgically treated patients with grade 4 RCC. Materials and methods: Using our institutional database of 1176 nephrectomies from 2005 to 2013, we identified patients with grade 4 RCC or any grade and the presence of sarcomatoid or rhabdoid differentiation. We divided the cohort based on differentiation: no differentiation, rhabdoid only, sarcomatoid only, and sarcomatoid and rhabdoid. CSS was analyzed using the Kaplan–Meier method and Cox proportional hazards modeling. Results: Of 264 patients with grade 4 RCC, 159 (60.2 %) exhibited differentiation, including 45 (28.3 %) with rhabdoid only, 87 (54.7 %) with sarcomatoid only, and 27 (16.9 %) with rhabdoid and sarcomatoid. Sarcomatoid differentiation, either alone or with rhabdoid differentiation, was associated with worse median CSS than no differentiation (1.1 vs. 3.3 years, p < 0.01, and 0.9 vs. 3.3 years, p < 0.01, respectively). In patients with non-metastatic (HR 1.95, 95 % CI 1.19–3.19, p = 0.008) and metastatic (HR 2.22, 95 % CI 1.45–3.41, p < 0.001) RCC, sarcomatoid differentiation was associated with an increased risk of cancer-specific death. On multivariable analysis, sarcomatoid differentiation was an independent predictor of RCC death in patients with non-metastatic (HR 1.72, 95 % CI 1.04–2.84, p = 0.03) and metastatic (HR 1.74, 95 % CI 1.05–2.90, p = 0.03) disease. Rhabdoid differentiation alone was not associated with worse CSS (p = 0.55). Conclusions: In grade 4 RCC, sarcomatoid differentiation is associated with increased mortality risk across all stages of disease. Rhabdoid differentiation is not associated with additional mortality risk.