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Survival Outcomes and Tumor IMP3 Expression in Patients with Sarcomatoid Metastatic Renal Cell Carcinoma
Srinivas K Tantravahi1, Daniel Albertson2, Archana M Agarwal2
1Department of Internal Medicine, University of Utah Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
Abstract:
Metastatic renal cell carcinoma with sarcomatoid histology (SmRCC) is associated with poor survival. No data is available from randomized trials on the efficacy of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors in SmRCC. We identified SmRCC patients from a single institutional database. To identify predictive and prognostic biomarkers, immunohistochemistry (IHC) analysis was performed on the tumor samples for downstream targets of VEGF and mTOR pathways. Survival outcomes were stratified by IHC analysis, extent of sarcomatoid component, Memorial Sloan-Kettering Cancer Center (MSKCC), and Heng risk criteria. Twenty-seven patients with SmRCC were included. First line therapy included targeted therapy (n = 19), immunotherapy (n = 4), cytotoxic chemotherapy (n = 1), and no treatment (n = 3). Median OS was 8.2 months (95% CI 3.8-14.2 months). Median survival in months, based on MSKCC and Heng risk groups, was favorable 89.3 versus 84.5, intermediate 9.5 versus 12.7, and poor 3.9 versus 5.1. None of the IHC markers predicted outcomes of treatment with VEGF or mTOR inhibitors. Only tumor IMP3 expression was associated with inferior OS, although not statistically significant (IMP3 negative 14.2 versus IMP3 positive 4.9 months; HR 0.46, 95% CI 0.16-1.21; P = 0.12). The study was limited by small sample size.
Insights
Metastatic renal cell carcinoma with sarcomatoid histology (SmRCC) has poor survival. This study found no biomarkers predicting treatment response, but IMP3 expression may indicate worse outcomes in SmRCC patients.
Area of Science:
- Oncology
- Cancer Biology
- Translational Research
Background:
- Metastatic renal cell carcinoma (mRCC) with sarcomatoid histology (SmRCC) presents a significant challenge due to poor prognosis.
- Limited data exists from randomized trials regarding the efficacy of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors in SmRCC.
Purpose of the Study:
- To investigate predictive and prognostic biomarkers for SmRCC.
- To evaluate survival outcomes in SmRCC patients treated with targeted therapies.
Main Methods:
- Retrospective analysis of 27 SmRCC patients from a single institutional database.
- Immunohistochemistry (IHC) performed on tumor samples for downstream targets of VEGF and mTOR pathways.
- Survival outcomes stratified by IHC markers, sarcomatoid component extent, and established risk criteria (MSKCC, Heng).
Main Results:
- Median overall survival (OS) was 8.2 months for SmRCC patients.
- No IHC markers reliably predicted treatment outcomes with VEGF or mTOR inhibitors.
- Tumor IMP3 expression showed a trend towards inferior OS (14.2 months for IMP3-negative vs. 4.9 months for IMP3-positive), though not statistically significant.
Conclusions:
- Biomarker analysis did not identify predictors for VEGF or mTOR inhibitor efficacy in SmRCC.
- IMP3 expression warrants further investigation as a potential negative prognostic marker in SmRCC.
- The small sample size limits definitive conclusions, highlighting the need for larger studies.
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