Extended Pharmacologic Prophylaxis for Venous Thromboembolism after Colon Cancer Surgery is Associated with Improved Long-term Survival: A Natural Experiment in the Chemotherapeutic Benefit of Heparin Derivatives.

ABSTRACT

OBJECTIVE: This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival. BACKGROUND: Heparin-derivatives may confer an anti-neoplastic effect via a variety of mechanisms (e.g. inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in post-surgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low. METHODS: Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for non-metastatic colon cancer from 2016-2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those that did not in an inverse propensity treatment weighted cohort. RESULTS: 20,102 patients were included in propensity-weighting and analyzed. 800 (3.98%) received extended pharmacologic prophylaxis. Overall and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests (P=0.0017 overall, P=0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [aHR 0.66 (0.56-0.78)] and cancer-specific survival [aHR 0.56 (0.39-0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors. CONCLUSIONS: Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential anti-neoplastic effect from heparin derivatives when used in the context of preventing post-surgical venous thromboembolism.