title: The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study.
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 pN0(micro+) 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 (pN0(micro+)) and evaluate the benefits from adjuvant chemotherapy in pN0(micro+) CC patients.
  
  
  METHODS
  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 (pN0(micro+)) are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01097265.
authors.affiliation: Department of Surgery, Jeroen Bosch Hospital, Nieuwstraat 34, 5211 NL 's-Hertogenbosch, The Netherlands. djlips@home.nl
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lips
authors.forename: Boukje
authors.initials: B
authors.lastname: Koebrugge
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Liefers
authors.forename: Johannes C
authors.initials: JC
authors.lastname: van de Linden
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.forename: Hans F M
authors.initials: HF
authors.lastname: Pruijt
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Koop
authors.initials: K
authors.lastname: Bosscha
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D002985:Clinical Protocols; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D021701:Sentinel Lymph Node Biopsy