Multifocal extramural venous invasion is a powerful predictor of adverse oncological outcomes in stages I-III colorectal cancer.

Aims: This study aimed to determine the impact of venous invasion (VI) characteristics on oncological outcomes in colorectal cancer (CRC).

Methods And Results: Resection specimens from 368 patients with TNM stages I-III CRC were assessed for VI including its presence/absence, location [intramural (IMVI) or extramural (EMVI)], number and size of the largest VI focus. VI and EMVI were identified in 55% and 32% of cases, respectively. EMVI, but not IMVI, was significantly associated with decreased 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) (hazard ratio [HR] 4.2, 95% confidence interval CI [2.6-6.9] and 3.7 [95% CI 1.9-6.9], p < 0.0001, respectively). Multifocal EMVI (mEMVI), defined as 2 or more EMVI foci, was identified in 67% of EMVI-positive cases. In multivariable analysis, EMVI (HR 2.4 [95% CI 1.3-4.3], P = 0.003) and mEMVI (HR 2.4 [95% CI: 1.3-4.4], P = 0.02) were independently associated with RFS and demonstrated stronger associations than all other examined features, including T and N stage. These associations were maintained when the cohort was expanded to include 113 patients who received neoadjuvant therapy in addition to the original 368 patients who had not ('expanded cohort', n = 481). An increasing number of EMVI foci was significantly associated with decreased RFS and DSS (P < 0.0001). Patients with >5 EMVI foci (n = 31) had a particularly poor prognosis with 5-year RFS and DSS of 29% and 56%, respectively. EMVI dimensions were not associated with oncological outcomes.

Conclusions: Extramural location and multifocality are features of VI strongly associated with adverse oncological outcomes. If externally validated, incorporation of EMVI multifocality into future reporting protocols merits consideration.