L. G. Leijssen1,2, A. M. Dinaux1,2, H. Kunitake1,2, L. G. Bordeianou1,2, D. L. Berger1,2 1Massachusetts General Hospital,General And Gastrointestinal Surgery,Boston, MA, USA 2Harvard School Of Medicine,Brookline, MA, USA
Introduction: ?Perineural invasion (PNI) is associated with adverse oncological outcomes in colorectal cancer. However, it’s often underreported and not considered in the TNM staging system. The aim of this study is to clarify the role of PNI in patients with non-metastatic colon cancer.?
Methods: Patients with stage I-III colon cancer who underwent elective surgery at our tertiary center between 2004-2014 were extracted from a prospectively maintained database (n=1090). Long-term outcomes were compared, and differences were determined by multivariable Cox regression models adjusted for stage and potential confounders. ?
Results: PNI was identified in 168 (15.4%) patients and associated with left-sided tumors, greater tumor size, and advanced disease. Histopathological features including extramural vascular invasion, large and small vessel involvement, and poor differentiation were correlated with PNI. Furthermore, recurrence rates were significantly higher in patients with PNI presence (P<0.001). This was mainly explained by a higher rate of distant recurrence (8.7% vs. 30.4%, P<0.001), with liver (14.9%), peritoneum (8.9%), and lung (8.3%) as the main sites of metastasis. The estimate 5-year overall (OS) and disease-free survival (DFS) were both worse in the PNI positive group (OS: 79.7% vs. 55.1%; DFS: 87.9% vs. 60.8%, both P<0.001). Patients with stage-II disease and PNI presence had significantly worse OS than stage-III patients with no PNI (P<0.001). However, adjuvant therapy reversed this adverse outcome to comparable OS (P0.205). Multivariate analysis demonstrated PNI as an independent predictor for both overall (HR 1.77, 95% CI: 1.31-2.40, P<0.001) and disease-free survival (HR 1.72, 95% CI: 1.20-2.54, P0.004).?
Conclusion: Our study supports the benefits of adjuvant therapy in stage-II colon cancer with PNI positivity. PNI presence is an independent and poor prognostic factor in non-metastatic colon cancer and should be considered as a factor in disease stratification.?