Can systemic inflammation at diagnosis predict benefit from primary resection in metastatic colorectal cancer (mCRC)?

Abstract

410 Background: In CRC, the tumor associated immune response can manifest as, (1) a good prognostic anti-tumor local (intra-tumoral) inflammatory response; or (2) a poor prognostic tumor promoting systemic inflammatory response. As suggested for renal cancer, the survival advantage associated with primary resection in mCRC patients (pts) might relate to modification of the tumor associated immune response, through reduction in tumor bulk and the resulting reduction in tumor promoting cytokines. We examine if systemic inflammation at diagnosis predicts benefit from primary resection in mCRC. Methods: A prospectively collected multi-disciplinary CRC database was used to explore clinicopathological data from pts diagnosed with de novo mCRC from Jan 2009 to Jul 2012. Evidence of systemic inflammation was defined as serum albumin (SA) <35g/L or neutrophil-lymphocyte ratio (NLR) >4 at diagnosis. Pts with primary resection >42 days from diagnosis were excluded. Survival analyses utilised the Kaplan-Meier method and log-rank test. Results: Of 212 pts diagnosed with mCRC, 154 (72%) had de novo mCRC. 92 (60%) of these underwent primary resection, 62 (40%) had primary left in situ. SA was available in 141 pts, 71 (50%) had SA <35g/L. NLR was available in all pts, 93 (60%) had NLR >4. Primary resection was associated with superior overall survival (OS): median 32.5mo v 8.4mo (HR 0.29, p<0.001). Systemic inflammation was associated with inferior OS using either SA <35g/L (median 8.4mo v 19.8mo, HR 2.54, p<0.001) or NLR >4 (median 16.8 mo v 13.1 mo, HR 1.59, p=0.03). There was no difference in OS advantages associated with primary resection in pts with SA <35g/L (HR 0.25, p<0.001) compared to normal SA (HR 0.28, p<0.001) at diagnosis; a non significant difference was observed for NLR ≤4 (HR 0.15, p<0.001) compared to NLR >4 (HR 0.42, p=0.001). Data regarding resolution of systemic inflammation following primary resection will be presented. Conclusions: Our study confirms the OS benefit from primary resection in mCRC and the adverse prognostic impact of systemic inflammation. Based on our current data, any benefit from primary tumour resection cannot be explained by an impact on the tumor associated immune response.