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

Abstract Importance The impact of antibiotics (ATBs) on the risk of colorectal cancer (CRC) recurrence after curative resection remains unknown. Objective We aimed to evaluate the effect of the type and the class of ATBs on recurrence in patients with resected non-metastatic CRC. Design Our cohort study included patients between 01/2012 and 12/2014. Each CRC patient was followed up to 3 years after surgical resection. Setting This study was conducted using extracted data from the French cancer cohort set up based on the National Health Data System by the French National Cancer Institute. Participants All newly diagnosed non-metastatic CRC patients resected were included. We excluded patients not affiliated to the major health insurance scheme in France (n=16 857) and with immunosuppression (n=32,359). Exposures 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). Main Outcome and Measure 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 mostly in patients with locally advanced stage and during chemotherapy (HR ranging from 1.22 to 1.41, P