Are the survival benefits associated with primary resection in de novo metastatic colorectal cancer (mCRC) mediated by reversal of systemic inflammation?

Abstract

464 Background: Despite reported survival benefits for primary tumor resection in de novo mCRC, its use remains controversial, particularly as the biological explanation remains unclear. We explored whether reversal of systemic inflammation, a marker of a tumor-promoting immune response and poor prognosis, is associated with improved survival in pts undergoing primary resection. Methods: We identified pts who underwent primary resection for de novo mCRC from a prospective CRC database, excluding pts who had metastatectomy. Neutrophil-lymphocyte ratio (NLR) was used to represent systemic inflammation. Survival differences associated with reversal of systemic inflammation, as defined by NLR falling from an elevated level (> 5) at diagnosis to ≤ 5 postoperatively, were examined. Associations between falling NLR and primary tumor bulk (maximal length assessed by pathologist) as well as metastatic burden (maximal axial diameter of largest metastasis assessed by radiologist) were explored. Results: Baseline and postoperative NLR were examined in 156 pts with median age 69y and median overall survival (OS) 18.3 mo. Baseline NLR was elevated in 66 (42%) pts; primary resection resulted in falling NLR in 37 of these pts (56%). Compared to pts with persistent NLR >5, a falling NLR was significantly associated with improved OS (HR 0.53, p = 0.012). Falling NLR was also associated with larger primary tumors, although this was not significant (median length 55mm vs. 45mm, p = 0.059). In a preliminary analysis of 26 pts with retrievable radiology, falling NLR was associated with lower metastatic burden compared to an unchanged NLR (median diameter 29mm vs. 41mm, p = 0.046). Conclusions: Our data demonstrates improved OS in pts who have reversal of systemic inflammation following primary resection in de novo mCRC. The possible associations between reversed systemic inflammation with larger primary tumors or a lower metastatic burden suggest an immune mediated response to reduced tumour bulk as an explanation for the reported survival advantage associated with primary resection. If confirmed, this might define a subgroup of pts who might benefit most from primary resection.