The document outlines the rationale and protocol for a study investigating micrometastases in pN0 colon cancer patients. It notes high recurrence rates in this group and aims to 1) improve risk stratification and 2) study the impact of adjuvant chemotherapy for pN0micro+ patients. The proposed study is a multicenter, randomized clinical trial that will examine lymph nodes from pN0 colon cancer patients using serial sectioning and immunohistochemistry to detect micrometastases, and randomize pN0micro+ patients to observation or adjuvant chemotherapy to evaluate 3-year disease-free survival.

1. RATIONALE AND PROTOCOL

7. RATIONALE OF THE STUDY Medisch Contact 2010

8. RATIONALE OF THE STUDY Steenbergen, EJSO 2009

9. RATIONALE OF THE STUDY Van der Zaag, EJSO 2009

10. RATIONALE OF THE STUDY Van der Zaag, EJSO 2009

30. EnRoute  PROTOCOL

31. RATIONALE OF THE STUDY

32. RATIONALE OF THE STUDY Cochrane.org

38. EnRoute  PROTOCOL STUDY DESIGN flow chart

39. EnRoute  PROTOCOL PRIMARY END-POINT - 3-year disease free survival (DFS) in study groups (proportion of patients without local or distant recurrence, or second primary colorectal cancer, during the defined period of time)

40. EnRoute  PROTOCOL INCLUSION CRITERIA Registration - histological proven colon cancer, clinically localized, judged potentially resectable for cure, without intraoperatively gross nodal involvement - radiological suspicion of colon cancer, clinically localized, judged potentially resectable for cure, without intraoperatively gross nodal involvement - written informed consent

41. EnRoute  PROTOCOL EXCLUSION CRITERIA Registration - age < 18 years - previous colorectal surgery - clinical tumor perforation or obstruction

42. EnRoute  PROTOCOL INCLUSION CRITERIA Randomization - pN0micro+ colon cancer patients (stage I/II, Dukes A/B) - patients deemed to be fit for chemotherapy treatment (WHO classification ≤ 1; ASA classification ≤ 2)

43. EnRoute  PROTOCOL EXCLUSION CRITERIA Randomization - high risk pN0 according to: LNN < 10, T4, perforation/obstruction, lymphangioinvasion - chemotherapy-related exclusion criteria

44. EnRoute  PROTOCOL CONSORT STATEMENT

48. EnRoute  PROTOCOL FOLLOW UP