Introduction:

Sarcomatoid differentiation in Renal Cell Carcinoma (sRCC) is well know to be a subtype with poor prognosis with a high rate of synchronous metastases at presentation; nonetheless, outcomes in a contemporary cohort of patients with localized sRCC are not well characterized in a population-based study. We sought to determine the clinical characteristics, temporal trends in prevalence, and survival outcomes in patients with in patients with localized sarcomatoid RCC.  

Methods:

From 2004-2019, all 440,230 cases of RCC were extracted from the National Cancer Database; of these, 3.3% (14713) had sarcomatoid differentiation. Trend analyses were conducted using Cochran-Armitage test of trend. Multivariable Cox Proportional-Hazards regression was used to determine the impact of clinical and pathologic characteristics on all cause mortality (ACM) in patients with non-metastatic sRCC. Overall Survival (OS) was computed with Kaplan-Meier analysis (KMA), with sub-analysis performed for patients with AJCC Prognostic Stages I-III (Stage). Clear cell histology was designated as reference histology for all analyses. p value < 0.05 was considered statistically significant.

Results:

Sarcomatoid differentiation increased from 1.9% in 2004 to 4.1% in 2019, average annual percentage change (AAPC) 0.060 (p<0.001). sRCC with synchronous metastasis decreased from 48.7% in 2004 to 38.7% in 2019, AAPC -0.028 (p<0.001). Of all sRCC, 44.0% had synchronous metastasis. On Cox regression for non-metastatic sRCC, ACM was associated with increasing age (HR=1.02, p<0.001), Charlson comorbidity (HR=1.27, p<0.001), lymphovascular invasion (HR=1.30, p<0.001), tumor grade (HR=1.30, p<0.001), and Stage 3 (HR=2.18, p<0.001); and inversely with minimally invasive (HR=0.21, p=0.008) and open (HR=0.30, p=0.042) partial nephrectomy. In non-metastatic sRCC, KMA showed 5-year OS was 52.9%; Substratification showed 5-year OS of 72.9% for Stage I, 60.4% Stage II, and 40.9% for Stage III sRCC (p<0.001; Figure).

Conclusion:

The findings constitute the largest retrospective characterization of localized RCC with sarcomatoid differentiation; sRCC has increased in prevalence, while patients presenting with synchronous metastases have decreased. Despite the latter trend, outcomes in patients with localized sRCC are poor and associated with patient comorbidity, stage, and associated histological findings. While partial nephrectomy was associated with improved outcomes, these findings must be interpreted with caution and are likely secondary to significant selection bias. Future studies investigating the underlying biology driving increased sarcomatoid differention despite generalized downward stage migration in RCC are requisite.

Funding: N/A