Open Access Study protocol

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

Daniel J Lips1*, Boukje Koebrugge12, Gerrit Jan Liefers2, Johannes C van de Linden3, Vincent THBM Smit4, Hans FM Pruijt5, Hein Putter6, Cornelis JH van de Velde2 and Koop Bosscha1

Author Affiliations

1 Department of Surgery, Jeroen Bosch Hospital, Nieuwstraat 34, 5211 NL 's-Hertogenbosch, the Netherlands

2 Department of Surgery, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands

3 Department of Pathology, Jeroen Bosch Hospital, Nieuwstraat 34, 5211 NL 's-Hertogenbosch, the Netherlands

4 Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands

5 Department of Medical Oncology, Jeroen Bosch Hospital, Nieuwstraat 34, 5211 NL 's-Hertogenbosch, the Netherlands

6 Department of Medical Statistics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands

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BMC Surgery 2011, 11:11  doi:10.1186/1471-2482-11-11

Published: 11 May 2011

Abstract

Background

The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC). In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0) will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs) and/or micrometastases (MMs) at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0micro+ patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0micro+) and evaluate the benefits from adjuvant chemotherapy in pN0micro+ CC patients.

Methods/design

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).

Discussion

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.

Trial Registration

ClinicalTrials.gov: NCT01097265