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Lymphovascular Invasion and Perineural Invasion Negatively Impact Overall Survival for Stage II Adenocarcinoma of the Colon

Skancke, Matthew, M.D.; Arnott, Suzanne M., B.S.; Amdur, Richard L., Ph.D.; Siegel, Robert S., M.D.; Obias, Vincent J., M.D., M.S.; Umapathi, Bindu A., M.D., M.R.C.S.

doi: 10.1097/DCR.0000000000001258
Original Contributions: Colorectal Cancer
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BACKGROUND: Lymphovascular invasion and perineural invasion are histopathological features associated with higher-risk colon cancer.

OBJECTIVE: The purpose of this study was to quantify the impact of lymphovascular and perineural invasion on overall survival after diagnosis and to determine the protective effect of adjuvant chemotherapy for early adenocarcinoma with high-risk factors.

DESIGN: This was a retrospective database review of the 2010–2014 National Cancer Database for colon cancer.

SETTINGS: Individuals diagnosed with invasive adenocarcinoma of the colon (histology code 8140) with primary surgical resection with >12 nodes harvested and no positive nodes on pathological examination were included.

PATIENTS: A total of 32,493 patients underwent surgical resection for stage II adenocarcinoma of the colon.

INTERVENTIONS: The study involved multivariate Cox regression analysis of the impact of lymphovascular and perineural invasion and adjuvant chemotherapy on overall survival after a diagnosis of stage II adenocarcinoma of the colon.

MAIN OUTCOME MEASURES: Survival after a diagnosis of stage II adenocarcinoma of the colon was measured.

RESULTS: Five-year survival after diagnosis and surgical resection without adjuvant chemotherapy was lower for patients with lymphovascular (60.0%), perineural (56.9%), and lymphovascular and perineural invasion (55.8%) compared with double-negative disease (66.1%). Log-rank testing confirmed that adjuvant chemotherapy improved 5-year survival after diagnosis for lymphovascular (85.5%), perineural (83.6%), and lymphovascular and perineural invasion (74.3%). After controlling for differences in cohorts, Cox regression analysis showed an increased HR for mortality of 14.0% for lymphovascular (HR = 1.141 (95% CI, 1.060–1.228)), 32.1% for perineural (HR = 1.321 (95% CI, 1.176–1.483)), and 41.0% for lymphovascular and perineural invasion (HR = 1.409 (95% CI, 1.231–1.612)) compared with having neither. Chemotherapy showed a 43% reduction in hazard for mortality (HR = 0.570 (95% CI, 0.513–0.633)).

LIMITATIONS: The study was limited by its retrospective review and observational bias.

CONCLUSIONS: Lymphovascular and perineural invasion have a detrimental effect on survival after diagnosis of stage II adenocarcinoma of the colon. Chemotherapy may be protective specifically when lymphovascular and perineural invasion are present. See Video Abstract at

Department of General Surgery and Colorectal Surgery at the George Washington University Hospital

Funding/Support: None reported.

Financial Disclosure: None reported.

Correspondence: Matthew Skancke, M.D., George Washington University Hospital, 22nd & I Street, NW, 6th Floor Suite 6B, Washington, DC 20037. E-mail:

© 2019 The American Society of Colon and Rectal Surgeons