Abstract

Background: Sarcomatoid differentiation/histology of renal cell carcinoma (sRCC) in patients with metastatic renal cell carcinoma (mRCC) is still underresearched in current therapy regimes. We aimed to evaluate the impact of sRCC on outcomes in patients with mRCC treated with tyrosine kinase inhibitors (TKIs).Methods: We collected complete data of 262 consecutive mRCC patients from our institutional database for this retrospective study. All patients were treated with TKIs within a single or multimodal treatment approach. All analyses were adjusted for the presence of sRCC. Descriptive statistics as well as uni- and multivariable outcome metrics, including progression-free (PFS) and overall survival (OS) as endpoints were performed.Results: Overall, 18 patients had sRCC (6.9%). Patients with sRCC had more often clear-cell histology (p = 0.047), a higher T-stage (p = 0.048), and underwent cytoreductive nephrectomy more frequently (p < 0.001). The most common first-line TKIs were Sunitinib (65.6%), Sorafenib (19.5%), and Pazopanib (10.3%), respectively. At a median follow-up of 32 months, patients with sRCC had significantly reduced PFS (p = 0.02) and OS (p = 0.01) compared to patients without sRCC. In multivariable analyses that adjusted for the effects of standard mRCC predictors, the sarcomatoid feature retained its independent association with inferior PFS (HR: 2.39; p = 0.007) and OS (HR: 2.37; p = 0.001). This association remained statistically significant in subgroup analyses of patients with Sunitinib as first-line therapy (PFS p < 0.001; OS: p < 0.001).Conclusion: Despite its rare occurrence, our findings confirm sRCC as a powerful predictor for inferior outcomes in mRCC treated with targeted therapies. This suggests a need for more tailored treatment strategies in patients harboring mRCC with sarcomatoid histology to improve oncological outcomes.

Highlights

  • Disease management for metastatic renal cell carcinoma has changed since the introduction of tyrosine kinase inhibitors (TKIs)

  • Sarcomatoid histology was present in 18 patients (6.9%) and the mean percentage of sarcomatoid features was 41% (5–95%) (Figure 1)

  • There was no difference in first- or second-line therapy, or treatment with cytoreductive nephrectomy, metastasectomy, or radiation therapy between patients with or without Sarcomatoid differentiation/histology of renal cell carcinoma (sRCC) histology

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Summary

Introduction

Disease management for metastatic renal cell carcinoma (mRCC) has changed since the introduction of tyrosine kinase inhibitors (TKIs). Histological subtypes and variants have shown prognostic value in mRCC [1, 2]. Sarcomatoid differentiation/histology of renal cell carcinoma (sRCC) is a histological variant that can occur in the primary tumor, metastases, or both with an incidence of 5–12% in patients with mRCC [3,4,5]. Sarcomatoid differentiation/histology of renal cell carcinoma (sRCC) in patients with metastatic renal cell carcinoma (mRCC) is still underresearched in current therapy regimes. We aimed to evaluate the impact of sRCC on outcomes in patients with mRCC treated with tyrosine kinase inhibitors (TKIs)

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