Prognostic factors in metastatic colorectal cancer
Authors: M. Silva, I. Guerreiro, S. Abreu, D. Marques
Journal: Annals of Oncology (2018)

Introduction: In addition to the predictive value of RAS complex status in metastatic colorectal cancer (MCRC), the impact of several clinicopathological characteristics in the outcome has been described, although the practice recommendations have not yet clearly separate algorithms. The purpose of this study is to identify features that affect natural history of disease in our population. Furthermore, we aim to analyze the difference between prognosis of mCRC according with the choice of initial biologic agent. Methods: This is a retrospective analysis of consecutive series of patients who presented with unresectable synchronous or metachronous mCRC, proposed for systemic first-line treatment combining chemotherapy with EGFR or VEGF-targeted therapy, between January 2014 and June 2015. Descriptive statistics were used to describe demographics and clinicopathological variables. Survival estimates were performed using Kaplan Meier method, and comparisons accomplished using log-rank, and association between nominal variables with person's correlation. Results: A total of 80 cases were included, with median age at diagnosis of mCRC 61 years (min 33, max 79 years), of whom 58 (72,5%) were males. Most patients had stage IV disease (n = 50, 62,5%), and 20 patients (25,1%) had stage III disease. Eastern Cooperative Oncology Group Performance Status was considered 0 or 1 in most patients (n = 78, 97,5%). In 44 cases (55%), tumors had wild type RAS complex status, and of these 39 (88,6%) were left sided primary lesions, while in RAS mutated tumors, 12 (33,3%) had primary origin in right colon, with statistically a significant association between sidedness and RAS complex status (p = 0.017). Among patients with RAS complex wild type tumors, median OS was 33 months (min 3, max 45 months) for patients treated with anti-EGFR in first setting, and was not achieved in those treated with anti-VEGF targeted agents. The choice of first line treatment did not influenced OS in left sided tumors, while all patients with RAS wild type and right sided tumors were treated with anti-EGFR treatment first. Considering the hole population study, OS of patients treated with anti-VEGF was 20 months (min 6, max 67 months). Among patients with RAS wild type tumors, 36,5% were considered to be suitable for curative surgery after systemic treatment, and submitted to metastasectomy while surgery was only performed in 8,3% of RAS mutated patients (p = 0,004). There was no significant difference in proportion of patients submitted to metastasectomy according to first line biological agent used. Regarding features that influenced OS, left sided primary tumor patients were associated with longer median OS (24 months, CI95%[19,1-28.8]) than right sided (19 months, CI95%[11,5-24.4]), with nearly statistical significance p = 0.05. Age (less than 70 years, p = 0,009), RAS complex wild type status (p < 0.001), and accomplishment of metastasectomy (p < 0.001) were associated with improved OS. Stage IV disease (versus initially localized disease), as well as burden of disease (more than 3 metastatic sites) were not associated with worse OS in our population. Conclusion: This report of prognostic factors of mCRC in our clinical practice is concordant with literature reports. Further studies in the future might integrate this in treatment algorithms, focusing in conversion to radical treatment