Comparison of histopathological features of high-risk stage II colon adenocarcinoma patients with stage III disease and their prognostic significance

Introduction: Factors that increase colon cancer recurrence and mortality are called high-risk features (HRF). NCCN guidelines list HRF as undifferentiated tumors, lymphovascular/perineural invasion, obstruction/perforation, <12 lymph nodes (LN), T4 disease, and positive surgical margins. Methods: A retrospective study was done on 377 patients with stage II/III colon adenocarcinoma at a single center from 2016 to 2020. Patients were grouped into stage II (<3 HRF and ≥3 HRF) and stage III. Results: Stage II ≥3 HRF patients (n=88) had higher lymphatic, plexus, perineural invasion, and 90-day mortality than stage III (n=187) (p<0.05). Stage III had higher vascular invasion, lower peritumoral Crohn-like lymphoid reaction, higher preoperative CEA and CA 19-9 (p<0.05). The 5-year overall survival (OS) and disease-free survival (DFS) rates were: stage II <3 HRF (79.4%, 74.5%), stage II ≥3 HRF (58.9%, 58.9%), and stage III (71.2%, 61.3%) (p=0.037, p=0.040). In subgroup analysis, there was no significant difference between stage II ≥3 HRFs and stage III in terms of OS (p=0.126) and DFS (p=0.600). In multivariate analysis, factors affecting OS were age ≥ 65, colostomy, <12 LN, and high CEA, while factors affecting DFS were age ≥ 65, colostomy, large tumor volume, <12 LN, high CEA, and stage III. Conclusion: Stage II ≥3 HRF colon adenocarcinomas had worse outcomes than stage II <3 HRFs and stage III, but in the subgroup analysis, there was no difference in survival between stage II ≥3 HRFs and stage III. This suggests that stage II ≥3 HRF cancers may behave similarly to stage III disease. Keywords: Colon cancer, high risk feature, adenocarcinoma