PB1444 - Survival effects of intraoperative thromboprophylaxis with low-molecular-weight heparin or heparin in patients undergoing colorectal cancer resection: A post-hoc analysis of PERIOP-01 trial

Background: Pre-clinical data suggested that heparin could inhibit fibrin and platelet coating of tumor cells and enable the detection and destruction by nature killer cells. Administration of low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) around the time of cancer resection surgery could initiate this process early and decrease the chance of metastasis. However, this hypothesis requires investigation.

Aims: To evaluate the effect of administrating LMWH or UFH prior to or in the operating room (OR) on the disease-free survival (DFS) in patients undergoing colorectal cancer resection.

Methods: This is a post-hoc analysis of the PERIOP-01 trial, a multi-center randomized controlled trial comparing extended duration (up to 6 weeks post-operatively) to standard duration (in hospital only) thromboprophylaxis with tinzaparin (4500 IU subcutaneously daily) in patients undergoing surgical resection for localized colorectal cancer. We compared patients who received one dose of LMWH or UFH at the time of surgery up to 12 hours before OR to those who did not. The primary outcome was DFS at 3 years. Cox-proportional hazards models were used adjusting for age, gender, and treatment allocation.

Results: A total of 614 patients were randomized, 307 to each treatment arm. 409 patients received LMWH or UFH around the time of OR, while 192 did not (excluding 12 who withdrew prior to surgery). The baseline characteristics of patients stratified by the use of anticoagulation and the treatment arm were summarized in Table 1. The 3-year DFS was 80.7% (330/409) in patients who received anticoagulation compared to 76.6% (147/192) in those who didn’t (adjusted HR 0.81, 95% CI 0.63-1.05, p=0.11) (Figure 1).

Conclusion(s): In the PERIOP-01 trial, receiving LMWH or UFH at the time of surgery up to 12 hours before OR was associated with a trend towards improved DFS at 3 years, although not statistically significant. This result is hypothesis-generating for future studies.
(NCT01455831)