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A Molecular Model for Predicting Overall Survival in Patients with Metastatic Clear Cell Renal Carcinoma: Results from CALGB 90206 (Alliance).

  • Author(s): Kim, Hyung L;
  • Halabi, Susan;
  • Li, Ping;
  • Mayhew, Greg;
  • Simko, Jeff;
  • Nixon, Andrew B;
  • Small, Eric J;
  • Rini, Brian;
  • Morris, Michael J;
  • Taplin, Mary-Ellen;
  • George, Daniel;
  • Alliance for Clinical Trials in Oncology
  • et al.
Abstract

Background

Prognosis associated with metastatic renal cell carcinoma (mRCC) can vary widely.

Methods

This study used pretreatment nephrectomy specimens from a randomized phase III trial. Expression levels of candidate genes were determined from archival tumors using the OpenArray® platform for TaqMan® RT-qPCR. The dataset was randomly divided at 2:1 ratio into training (n = 221) and testing (n = 103) sets to develop a multigene prognostic signature.

Findings

Gene expressions were measured in 324 patients. In the training set, multiple models testing 424 candidate genes identified a prognostic signature containing 8 genes plus MSKCC clinical risk factors. In the testing set, the time dependent (td) AUC for a prognostic model containing the 8 genes with and without MSKCC risk factors were 0.72 and 0.69, respectively. The tdAUC for the clinical risk factors alone was 0.61. Additional primary mRCCs from patients with mRCC (n = 12) were sampled in multiple sites and standard deviations of gene expressions within a tumor were used as a measure of heterogeneity. All 8 genes in the final prognostic model met our criteria for minimal heterogeneity.

Conclusions

A molecular prognostic signature based on 8 genes was developed and is ready for external validation in this patient population and other related settings such as nonmetastatic RCC.

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