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Updated: Feb 2, 2026
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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
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Genomically annotated risk model for advanced renal-cell carcinoma: a retrospective cohort study
Martin H Voss1, Albert Reising2, Yuan Cheng2
1Memorial Sloan Kettering Cancer Center, New York, NY, USA.
The Lancet. Oncology
|November 13, 2018
Summary
This study enhances the Memorial Sloan Kettering Cancer Center (MSKCC) risk model for metastatic renal-cell carcinoma by incorporating tumor genomics. Adding BAP1, PBRM1, and TP53 mutation status improves prognostic accuracy for overall survival and progression-free survival.
Area of Science:
- Oncology
- Genomics
- Cancer Prognostics
Background:
- The Memorial Sloan Kettering Cancer Center (MSKCC) risk model is a standard prognostic tool for metastatic renal-cell carcinoma (mRCC).
- Current models do not integrate tumor genomics, despite known prognostic value of mutations like BAP1 and PBRM1 in renal-cell carcinoma.
- There is a need to enhance prognostic models for mRCC by incorporating genomic data.
Purpose of the Study:
- To investigate if adding the mutation status of key prognostic genes to the MSKCC risk model improves its prognostic performance in mRCC.
- To develop a genomically annotated risk model for mRCC.
Main Methods:
- Retrospective cohort study using two independent clinical trial datasets (COMPARZ and RECORD-3) of treatment-naive mRCC patients receiving tyrosine kinase inhibitors.
- Somatic mutations in six candidate genes (BAP1, PBRM1, TP53, TERT, KDM5C, SETD2) were analyzed using next-generation sequencing in the training cohort.
- Prognostic value of mutations was assessed, and significant genes were incorporated into the MSKCC model to create a genomically annotated version, which was validated.
Main Results:
- In the training cohort, mutations in BAP1, TP53, and PBRM1 showed independent prognostic value for overall survival.
- The genomically annotated MSKCC model demonstrated improved performance in predicting overall survival (C-index 0.637 vs 0.595) and progression-free survival (0.602 vs 0.567) compared to the original model.
- The enhanced model reclassified a significant proportion of patients into different risk groups, with superior performance confirmed in the validation cohort.
Conclusions:
- The mutation status of BAP1, PBRM1, and TP53 provides independent prognostic information in advanced or metastatic renal-cell carcinoma patients treated with first-line tyrosine kinase inhibitors.
- A genomically annotated risk model incorporating these mutations offers improved patient stratification compared to the traditional MSKCC model.
- This enhanced model warrants further investigation in prospective trials for stratifying mRCC patients in clinical settings.
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