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Impact of Extramural Vascular Invasion on Colon Cancer Outcomes
Ramzi Amri*2, Liliana G. Bordeianou1,2, David L. Berger1,2
1General and Gastrointestinal Surgery, Harvard Medical School/Massachusetts General Hospital, Cambridge, MA; 2Surgery, Harvard Medical School, Boston, MA

Objective: Extramural vascular invasion (EMVI) is a pathologic characteristic that has been extensively studied in rectal cancer. This study aims to evaluate its validity as a prognostic factor in colon cancer patients without distant metastasis.
Design: Retrospective review of a prospectively maintained, IRB-approved data repository.
Setting: Tertiary care center.
Patients: All colon cancer patients treated surgically at our center from 2004 through 2011 were included, excluding patients with metastatic disease confirmed within 30 days of the index admission.
Main outcome measures: Survival and recurrence in follow-up.
Results: A total of 843 patients were included for analysis, among which 197 (23.4%) had extramural vascular invasion (range 2.3% in stage I to 44.7% in stage III). In all three stage increments, EMVI-positive patients had considerably higher rates of metastatic recurrence (stage I: 33.3% vs. 1.9%, stage II: 26.4% vs. 8.9%, stage III: 35.2% vs. 17.9%; all P<0.001) and colon cancer-specific mortality (stage I: 33.3% vs. 2.3%, stage II: 20.3% vs. 3.4%, both P<0.001, stage III: 26.2 vs. 13.9%; P=0.01). Across stages, a multivariable Cox regression showed the hazard ratio (HR) for mortality, adjusted for age, baseline stage, adjuvant chemotherapy, comorbidity and smoking status to be HR=2.05 (P<0.001), while stage-adjusted disease-free survival was HR=2.82 (P<0.001).
Conclusion: Extramural vascular invasion is an important predictor of metastatic recurrence and mortality in all stages of surgically treated colon cancer patients without baseline metastasis. It is also associated with worse outcomes within patients of the same stage. The magnitude of this effect is such that even in stage I patients, the option of adjuvant chemotherapy should be considered if extramural vascular invasion is present.
Stage I patientsEMVI +
(n=6; 2.3%)
(n=259; 97.7%)
RR (95%CI)P-value
Metastatic recurrence33.3%1.9%17.3 (4.2-71.8)<0.001
Overall survival66.7%79.5%1.63 (0.51-5.18)0.44
3-year survival66.7% (4/6)86.9% (193/222)2.55 (0.78-8.32)0.153
5-year survival66.7% (4/6)77.2% (132/171)1.46 (0.46-4.68)0.55
Colon cancer mortality33.3%2.3%14.4 (3.62-57.2)<0.001
Stage II patients EMVI +
(n=69; 22.6%)
(n=236; 77.8%)
RR (95%CI)P-value
Metastatic recurrence24.6%8.9%2.77 (1.55-4.95)0.001
Overall survival49.3%76.3%2.13 (1.54-2.96)<0.001
3-year survival62.9% (39/62)86.5% (180/208)2.76 (1.72-4.42)<0.001
5-year survival42.3% (22/52)79.3% (138/174)2.54 (1.80-3.59)<0.001
Colon cancer mortality20.3%3.4%5.99 (2.61-13.7)<0.001
Stage III patients EMVI +
(n=122; 44.7%)
(n=151; 55.3%)
RR (95%CI)P-value
Metastatic recurrence35.2%17.9%1.97 (1.30-2.99)0.001
Overall survival54.9%66.9%1.36 (1.01-1.84)0.043
3-year survival52.3%(57/109)73.3%(103/140)1.41 (1.06-1.89)0.001
5-year survival37.5%(33/88)63.4%(78/123)1.54 (1.17-2.01)<0.001
Colon cancer mortality26.2%13.9%1.89 (1.15-3.09)0.010
Cox regression*
(Stages I-III)
CovariablesHR (95%CI)P-value
SurvivalStage, Age, Adj. chemo, comorbidity, smoking2.05 (1.54-2.75)<0.001
Disease-free survivalAJCC stage2.82 (1.88-4.23)<0.001

* Covariables selected using backward conditional elimination among the following: Adjuvant chemotherapy, Age, Baseline AJCC 7th edition staging, Charlson comorbidity score excluding for colon cancer, and smoking status.
Abbreviations: EMVI: Extramural Vascular Invasion; RR: Relative Risk for negative outcome (mortality, recurrence); HR: Hazard Ratio. Survival and disease-free survival, in months.

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