Trends in epidemiology, treatment and molecular testing of metastatic colorectal cancer in a real-world multi-institution cohort study

Abstract

Aim: Colorectal cancer (CRC) is the third most common cancer in Australia, and survival after diagnosis of metastatic disease is improving. Our aim was to assess trends in epidemiology, treatment, molecular testing and survival in patients with metastatic CRC (mCRC).

Methods: Clinical data from February 2013 to December 2018 was recorded in a prospective, observational, multicenter cohort study conducted in Queensland, Australia, examining clinical and molecular biomarkers in cases of mCRC.

Results: A total of 159 patients who had metastasis diagnosed after February 2013 were included in survival analysis. Median age at diagnosis was 63.9 years, but 29% had early-onset disease (diagnosis aged <50 years). Median overall survival was 2.5 years (95% confidence interval [CI], 2.2-3.0) for the 159 patients included in survival analysis. Independent factors correlated with poor prognosis included right-sided primary tumor, neutrophil-lymphocyte ratio >5, increased alkaline phosphatase level (ALP) and an increasing number of sites of metastatic disease. In contrast, metastasectomy was associated with improved overall survival (adjusted HR = 0.29' 95% CI, 0.16-0.54), with similar survival between patients who had liver and non-liver metastasectomy sites. Half (10/20) of the BRAF mutant CRC were also microsatellite unstable. The proportion of detected mutations amongst tested samples increased over time for Kirsten Rat Sarcoma (KRAS; OR [per year] = 1.19; 95% CI, 1.01-1.39). Concurrently, the methods of molecular genetics testing employed in routine clinical practice changed towards the adoption of next-generation sequencing.

Conclusions: Metastasectomy in mCRC may be beneficial regardless of the anatomical site of metastasis. The adoption of next-generation sequencing techniques for molecular genetics testing coincided with a slightly increased rate of detection of KRAS and BRAF mutations, potentially reflecting greater test sensitivity. Further translational research is required in mCRC to define novel targets for treatment.

Keywords: cancer epidemiology; cancer genetics; colorectal; medical oncology; registry.