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Aims: Patients with inflammatory bowel disease (IBD) who develop colorectal cancer (CRC) have poorer outcomes, reasons for which remain unclear. Cancer-associated-inflammation is a key determinant of disease progression and survival in colorectal cancer. Inflammation measured locally and in the systemic circulation, has not previously been examined in a cohort of Inflammatory bowel disease-associated colorectal cancers. The aim of the present study was to compare clinico-pathological characteristics and survival in those with an IBD history and those without. In particular the role of local and systemic inflammatory responses in determining outcome was assessed.
Methods: Patients were identified from a database of colorectal cancer patients undergoing surgery between 1997-2009. Systemic inflammation was measured using neutrophil:lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS: C-RP and albumin). Local tumour inflammation was measured with the Klintrup criteria.
Results: 755 pts were included, 57 of which had Inflammatory bowel disease. IBD patients developed Colorectal cancer at a younger age (64vs70yrs,P<0.005). Despite similar stage and tumour location to non-IBD cancers, IBD associated tumours displayed higher risk pathology including poor differentiation (P<0.001), signet ring cell pathology (P<0.05), serosal involvement (P<0.005), tumour perforation (<0.001), and high-risk Gloucester prognostic index (P<0.001). Higher-grade local inflammation (evidenced by Klintrup criteria: P<0.05) and higher-grade systemic inflammation (evidenced by NLR (P<0.001) and GPS, P<0.001) were observed in IBD patients.
Median follow up was 53months (303 deaths). IBD patients had poorer overall survival (5-year survival 14% vs 41%, P<0.005). When considered with age (HR1.59, P<0.001), TNM stage (HR1.94,P<0.001) and GPS (HR1.58,P<0.001), history of IBD was an independent prognostic factor (HR1.99, P=0.001). Even within the IBD cohort, local inflammation (P=0.003) and systemic inflammation (GPS, P=0.001) remained strong predictors of overall survival.
Conclusions: Poorer survival in Inflammatory bowel disease-associated colorectal cancer may relate to higher frequency of high risk pathological characteristics as well as higher levels of cancer associated inflammation. Despite this close association, systemic inflammation remains an independent prognostic factor on multivariate analysis.