Abstract

Extramural venous invasion (EMVI) is considered an indicator of poor prognosis in patients who have undergone resection of primary colorectal cancer (CRC), but its use has not been widely adopted in staging systems or nomograms. In particular, EMVI is not reported in most large case series, is not included in most large CRC databases, and is not incorporated into the current AJCC TNM staging system. Staining for elastin may facilitate the accurate detection of EMVI and minimize inter-observer variability. We examined the prognostic potential of EMVI detected by elastin staining at a tertiary center that performs a high volume of CRC resections. This is a single-institution, observational study of consecutive patients who underwent resection of primary CRC between 01/01/2011 and 31/12//2016. All pathology specimens were re-assessed by reviewers who were blinded to patient outcomes. Venous invasion was detected using an elastin trichrome stain and classified as Intramural or Extramural. Overall and disease-specific survival (OS, DSS) were estimated using the Kaplan-Meier method. Differences between groups were assessed using the Mantel-Cox log-rank test. For the present analysis, we excluded all patients with stage IV (n=80) or IIIC (n=34) CRC. The cohort for analysis included 428 patients (248M, 190F; AJCC 8th edition Stage I n=107; Stage II n=185; Stage IIIA and B n=146) with a median follow-up time of 61 months (0.1-104). For the entire cohort, OS and DSS at 5 years were 82% and 90%, respectively. AJCC stage (p=0.04), but not T stage (p=0.08) or N stage (p=0.09), was prognostic of DSS. Neither grade (p=0.1) nor IMVI (p=0.4) were prognostic, whereas EMVI was highly prognostic of inferior DSS (p< 0.001). In this cohort of Stage I - III CRC patients with complete follow-up, EMVI as assessed by elastin staining was a powerful predictor of death from CRC. Elastin staining, which improves the accuracy and objectivity of EMVI detection, may allow validation of EMVI as an independent prognostic variable that should be incorporated into staging systems and nomograms. Accurate assessment of EMVI would permit refinement of risk estimation, and inform individualized decision-making regarding adjuvant therapy in patients who have undergone resection of CRC.

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