Association between the antibiotics use and recurrence in patients with resected colorectal cancer: EVADER-1, a nation-wide pharmaco-epidemiologic study.

ABSTRACT

BACKGROUND: The impact of antibiotics (ATBs) on the risk of colorectal cancer (CRC) recurrence after curative resection remains unknown. METHODS: Using the French nation-wide database of cancer patients, all newly diagnosed non-metastatic CRC patients resected between 01/2012 and 12/2014 were included. The perioperative ATB intake (from 6 months before surgery until 1 year after) was classified according to the class, the period of use (pre- vs post-resection), the disease stage (localized and locally advanced), and the primary tumor location (colon and rectum/junction). The primary endpoint was the 3-year disease-free survival (DFS). The impact of ATB was assessed using time-dependent multivariate Cox models. RESULTS: A total of 35,496 CRC patients were included. Seventy-nine percent of patients had at least one ATB intake. Outpatient ATB intake after surgery was associated with unfavorable 3-year DFS. The ATBs associated with decreased 3-year DFS were cephalosporins, streptogramins, quinolones, penicillin A with beta-lactamase inhibitors, and antifungals with differential effects according to the primary tumor location and disease stage. CONCLUSION: These findings suggest that ATBs modulate the risk of recurrence after early CRC resection with a differential impact of the ATB classes depending on disease stage and tumor site.