Prognostic Value of Molecular Biomarkers in Patients With Metastatic Colorectal Cancer: A Real-World Study

Purpose: Outcomes for patients with metastatic colorectal cancer (mCRC) have been improved by the identification of biomarkers predictive and prognostic of clinical outcome. The present retrospective analysis was undertaken to assess the utility of key biomarkers and clinical parameters in predicting outcomes in Spanish patients with mCRC.

Methods: We retrospectively analyzed tumor samples from a series of patients aged > 18 years with mCRC who were treated at the Hospital General Universitario Gregorio Marañón Spain. Real-time polymerase chain reaction was used to detect KRAS, NRAS, BRAF, and PIK3CA mutations. The key outcome of interest was overall survival (OS). Survival curves were estimated using the Kaplan-Meier method and stratified by the variables of greatest clinical interest. Differences were tested using the log-rank test.

Results: Median OS in the overall population was 24.4 months. Triple WT patients (WT KRAS, NRAS, and BRAF) and quadruple WT patients (WT KRAS, NRAS, BRAF, and PIK3CA) had significantly better OS than those who did not have triple or quadruple WT tumors. OS was significantly better in patients with left- vs. right-sided tumors, patients with resected primary tumors and metastases vs. those without resection, and patients with isolated hepatic and isolated pulmonary metastases.

Conclusions: This retrospective, observational study has confirmed the prognostic value of the location and resection status of the primary tumor and metastases in Spanish patients with mCRC. Triple WT status, in particular, was prognostic in this patient population, with PIK3CA adding to the prognostic value in the quadruple WT population.

Keywords: BRAF; Biomarkers; Colorectal cancer; PIK3CA; Prognostic; RAS.