Postoperative Day 2 C-reactive Protein Identifies Patients at Low Risk of Anastomotic Leakage After Colon Cancer Resection

OBJECTIVE: To determine whether C-reactive protein (CRP) <100 mg/L on postoperative day (POD) 2 excludes anastomotic leakage (AL) after colon cancer resection. SUMMARY BACKGROUND DATA: CRP <100 mg/L on POD3 is widely used to exclude AL, but enhanced recovery after surgery (ERAS) increasingly discharges patients before POD3, highlighting the need for an earlier biochemical criterion. METHODS: This two-cohort multicenter diagnostic accuracy study included patients undergoing elective colon cancer resection with primary anastomosis. AL was defined as Clavien-Dindo grade ≥3. POD2 CRP <100 mg/L was evaluated for excluding AL. In patients with POD2 CRP ≥100 mg/L, POD3 dynamics were evaluated using a POD3/POD2 ratio <1. RESULTS: AL occurred in 4.0% and 4.7% of patients in test (n=401) and validation (n=213) cohorts. POD2 CRP <100 mg/L was present in 240 (60%) and 97 (46%) patients, with AL in only 1.3% and 1.0%, yielding negative predictive values (NPVs) of 98.8% and 99.0%. In contrast, AL occurred in 8.1% and 7.8% of patients with POD2 CRP ≥100 mg/L. In the combined cohort, a POD3/POD2 ratio <1 further stratified risk among these higher-risk patients, with NPVs of 98.9% and 97.9% for minimally invasive and open surgery, respectively, and using this two-step strategy, nearly 90% of patients could be discharged by POD2 or 3 with AL risk near 1%. CONCLUSIONS: POD2 CRP <100 mg/L, supplemented by selective POD3 reassessment, provides a simple algorithm to support safe early discharge after colon cancer resection within ERAS pathways.