Risk of lymph node metastasis in T1 colorectal cancer with isolated deep submucosal invasion: a multicenter European study

Background Advances in colorectal cancer (CRC) screening and endoscopic techniques have led to increased detection of T1 CRC. Patient management relies on histopathological criteria predicting lymph node metastasis (LNM), including submucosal invasion depth (SID) >1000 µm. However, the independent prognostic value of isolated deep invasion remains unclear. Methods We performed a retrospective multicenter study of patients treated at 18 European centers between 2009 and 2022. Patients with T1 CRC endoscopically resected en bloc and with isolated SID >1000 µm (without other high-risk features) were included. Two groups were analyzed: patients who underwent additional surgery and those who were followed with surveillance. Rates of LNM (surgery group) and recurrence (local and distant; surveillance group) were assessed. Exploratory multivariable analyses were performed to evaluate clinicopathological factors associated with LNM. Results Among 179 included patients (124 surgery, 55 surveillance), LNM was found in 16/124 surgical specimens (12.9%; 95%CI 7.7–20.4) and recurrence occurred in 2/55 patients undergoing surveillance (3.6%; 95%CI 0.4–12.6). LNM occurred in 1/50 patients (2.0%) with SID <2000 µm and in 15/74 patients (20.3%) with SID ≥2000 µm. Multivariable analysis revealed SID ≥2000 µm (odds ratio [OR] 3.59; 95%CI 1.14–13.71) and colonic (vs. rectal) tumor location (OR 3.63; 95%CI 1.07–16.77) as factors associated with LNM. Conclusion Isolated deep submucosal invasion in T1 CRC was associated with a non-negligible rate of LNM in this real-world cohort. In exploratory analyses, SID ≥2000 µm was associated with LNM.