Biomarkers in renal-cell carcinoma: building on clinical paradigms.

Several models for prognostic stratification of patients with metastatic renal-cell carcinoma have been reported. The two most widely used models are the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models.1

The MSKCC model, which was developed in 1999, when cytokine therapy was standard of care, stratifies treatment-naive patients on the basis of five clinical and laboratory factors. Meanwhile, the IMDC model was developed in the context of VEGF-targeted therapy and stratifies patients on the basis of six factors, four of which are shared with the MSKCC model. These models have a valuable role in prognostication and counselling of patients with metastatic renal-cell carcinoma and in designing clinical trials by providing estimates for expected overall survival. In the past few years, the utility of risk categorisation of patients with advanced renal-cell carcinoma has expanded into treatment algorithms. Two examples are cabozantinib and the combination regimen of nivolumab plus ipilimumab, both of which were approved on the basis of their improved activity over sunitinib in treatment-naive patients with metastatic renal-cell carcinoma who are in intermediate and poor IMDC risk categories. 3

However, both models use only clinical and laboratory parameters and do not incorporate genomic data, despite comprehensive genomic profiling of tumour tissue being increasingly available in clinics and with decreasing costs. Hence, now is an opportune time to integrate tumour mutational status into these prognostic models.

References:
1.Motzer RJ Mazumdar M Bacik J Berg W Amsterdam A Ferrara JSurvival and prognostic stratification of 670 patients with advanced renal cell carcinoma.
J Clin Oncol. 1999; 17: 2530-2540


2.Heng DY Xie W Regan MM et al.External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study.
Lancet Oncol. 2013; 14: 141-148

3.Choueiri TK Halabi S Sanford BL et al.Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN Trial.
J Clin Oncol. 2017; 35: 591-597


4.Motzer RJ Tannir NM McDermott DF et al.Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma.
N Engl J Med. 2018; 378: 1277-1290



The Lancet. Oncology. 2018 Nov 08 [Epub]  DOI:https://doi.org/10.1016/S1470-2045(18)30674-0

Neeraj Agarwal, Roberto Nussenzveig, Sumanta K Pal. Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84112, USA. Electronic address: ., Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84112, USA., Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.