The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years) without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease) and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an ex vivo sentinel lymph node mapping procedure (SLNM) following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0micro+) are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS).The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 micro+ CC patients by reducing disease recurrence by adjuvant chemotherapy.ClinicalTrials.gov: NCT01097265Colorectal cancer is the second most commonly diagnosed malignancy in men and women in the Netherlands with increasing incidence due to growth and ageing of the general population [1]. The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC) [2]. Interestingly, in a large percentage of patients without lymph node metastases in the surgical specimen, who are therefore not subjected to adjuvant chemotherapy, represent with disease recurrence. In about 10% of the patients with stage I (Dukes A) and 15-30% with stage II (Dukes B) disease recurrent locoregional or distant metastases develop within 5 years [2-4]. One possible factor could be the presence of occult lymph node metastases at the time of presentation and surgical resection. Evidence has emerged showing a significant amount of nodal metastases being smaller than 2 mm or less (<0.2 mm isola