Underdiagnosis of positive resection margins and synchronous peritoneal metastases in locally advanced colon cancer: histopathological reassessment of primary resection in the COLOPEC trial

The aim of this study was to perform histopathological reassessment of primary resections of locally advanced colon cancer (CC) within a randomized controlled trial, with specific focus on surgical margins and synchronous locoregional peritoneal metastases (SL-PM), and to provide learning points for both surgeons and pathologists. All histopathological slides of patients with c/pT4N0-2M0 or perforated CC included in the COLOPEC trial were reassessed and correlated with surgical reports. The COLOPEC trial originally determined the value of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC). Frequency of positive margins (R +), R + subtypes, and SL-PM and the association with 5-year peritoneal recurrence were analyzed. Histopathological slides of 199 patients were reassessed. R + was present in 28 patients (14.1%), of which 8 occurred at the site of adhesiolysis (originally classified as pT4a in 6). SL-PM was present in 11 cases (5.5%), of which 9 were not recognized or misclassified. Both R + and SL-PM were associated with 5-year peritoneal metastases in cox regression analysis (HR 2.38, 95% CI 1.12-5.04 and HR 5.98, 95% CI 2.69-13.29, respectively). Of 9 patients with peritoneal recurrences detected during re-exploration at 5-8 weeks after primary tumor resection for intended HIPEC, 5 demonstrated either R + and/or SL-PM. This study brings to light previously unnoticed but clinicopathologically relevant aspects of CC pathology retaining to underdetected SL-PM and new R + types. Underrecognition until now probably relates to the complexity of advanced CC specimens, poor communication between surgeons and pathologists, and the low incidence among high volumes of CC specimens. Trial registration: NCT02231086 (Clinicaltrials.gov).