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Updated: Oct 11, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Treatment and Outcome of Metastatic Renal Cell Carcinoma With Sarcomatoid Differentiation: A Single-Center,
Florian Janisch1,2, Christina Kienapfel1, Constantin Fühner1
1Department of Urology, Medical University of Hamburg, Hamburg, Germany.
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.
Insights
Sarcomatoid renal cell carcinoma (sRCC) in metastatic renal cell carcinoma (mRCC) patients is rare but significantly predicts worse outcomes with tyrosine kinase inhibitor (TKI) therapy. This highlights the need for tailored treatment strategies for sRCC patients.
Area of Science:
- Oncology
- Medical research
- Renal cell carcinoma
Background:
- Sarcomatoid differentiation/histology (sRCC) in metastatic renal cell carcinoma (mRCC) is understudied in current therapeutic approaches.
- The impact of sRCC on treatment outcomes in mRCC patients receiving tyrosine kinase inhibitors (TKIs) requires further investigation.
Purpose of the Study:
- To evaluate the prognostic impact of sarcomatoid histology on treatment outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs).
- To determine if sRCC is an independent predictor of progression-free survival (PFS) and overall survival (OS) in mRCC patients undergoing TKI therapy.
Main Methods:
- Retrospective analysis of a cohort of 262 consecutive mRCC patients treated with TKIs.
- Data collected included patient demographics, histology, T-stage, cytoreductive nephrectomy status, and first-line TKI therapy.
- Uni- and multivariable analyses were performed to assess the association between sRCC and outcomes (PFS, OS), adjusting for known mRCC predictors.
Main Results:
- Sarcomatoid histology was identified in 18 patients (6.9%) and was associated with clear-cell histology, higher T-stage, and more frequent cytoreductive nephrectomy.
- Patients with sRCC exhibited significantly reduced progression-free survival (PFS) and overall survival (OS) compared to those without sRCC (p=0.02 and p=0.01, respectively).
- Multivariable analysis confirmed sRCC as an independent predictor of inferior PFS (HR: 2.39; p=0.007) and OS (HR: 2.37; p=0.001), even in subgroup analyses of Sunitinib users.
Conclusions:
- Sarcomatoid differentiation in mRCC, although rare, is a significant predictor of poor outcomes in patients treated with targeted therapies like TKIs.
- The findings underscore the need for developing specialized treatment strategies for mRCC patients with sarcomatoid histology to improve oncological outcomes.
- Further research into the biological mechanisms and therapeutic vulnerabilities of sRCC is warranted.
