Abstract
BackgroundMolecular assessment and treatment of metastatic colorectal cancer (mCRC) quickly evolved during the last decades, hampering longitudinal evaluation of prognostic markers. The aim of this study was to evaluate prognostic predictors of long-term survival in a retrospective series of mCRC, treated prior to the expanded RAS assessment era.MethodsmCRC cases treated at the Città della Salute e della Scienza University Hospital (Turin, Italy) between January 2004 and December 2012 were evaluated, including cases with ≥ 5-year follow-up only. Long-term survival was defined as an overall survival (OS) ≥ 4 years based on the observed OS interquartile range values. Univariate/multivariate Cox proportional hazards regression models were performed to assess the prognostic significance of the clinical/biological features, while binary logistic regression models were used to verify their associations with long-term survival.ResultsTwo hundred and forty-eight mCRC cases were included and analyzed. Sixty out of two hundred and forty-eight (24%) patients were long-term survivors. Univariate binary logistic regression analysis demonstrated a significant association between long-term survival and age at diagnosis < 65 (OR = 2.28, p = 0.007), single metastatic site (OR = 1.89, p = 0.039), surgical resection of metastases (OR = 5.30, p < 0.001), local non-surgical treatment of metastases (OR = 4.74, p < 0.001), and a bevacizumab-including first-line treatment schedule (OR = 2.19, p = 0.024). Multivariate binary logistic regression analysis confirmed the prognostic significance of surgical resection of metastases (OR = 3.96, p < 0.001), local non-surgical treatment of metastases (OR = 3.32, p = 0.001), and of bevacizumab-including first-line treatment schedule (OR = 2.49, p = 0.024).ConclusionLong-term survival could be achieved in a significant rate of patients with mCRC even in an era of limited molecular characterization. Local treatment of metastases proved to be a significant predictor of long-term survival.
Highlights
Molecular assessment and treatment of metastatic colorectal cancer quickly evolved during the last decades, hampering longitudinal evaluation of prognostic markers
The clinical and histopathological heterogeneity of Colorectal cancer (CRC) has been further supported by molecular profiling and specific mutational profiles resulted to be strongly correlated with clinical outcome and response to treatment [5]
To define long-term survivors (LTS), a survival time ≥ 4 years was selected based upon the observed overall survival interquartile range (IQR) values (1.54–4.00 years): this cutoff value enabled to have a representative number of cases available for the subsequent analyses while being a clinically meaningful time period
Summary
Molecular assessment and treatment of metastatic colorectal cancer (mCRC) quickly evolved during the last decades, hampering longitudinal evaluation of prognostic markers. The aim of this study was to evaluate prognostic predictors of long-term survival in a retrospective series of mCRC, treated prior to the expanded RAS assessment era. Initial disease stage remains the main outcome predictor in CRC, in the precision medicine era, tumor molecular profiling has become of paramount importance [4]. Assessment of specific tumor characteristics and biomarkers [e.g., tumor site (right versus left colon), mismatch repair capability, KRAS, NRAS, and BRAF proto-oncogenes mutational statuses] is deemed mandatory for treatment selection in patients with mCRC, and the main therapeutic options in this setting include chemotherapy drugs, targeted therapies against the EGFR (Epidermal Growth Factor Receptor), and VEGF (Vascular Endothelial Growth Factor) pathways and immunotherapy [6]
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