Lymph node staging in colon cancer

The prognosis of patients with colon cancer is generally related to the degree of invasion of the tumor through the bowel wall and the presence or absence of lymph node involvement and distant metastases. Adjuvant chemotherapy is given to patients with lymph node metastases (stage II) and some patients without nodal metastases but with certain unfavorable tumour characteristics. Despite the good prognosis of patients without lymph node metastases (stage II colon cancer), 20-30% of these patients will develop recurrent disease, even after apparently curative resection.1 In this thesis an attempt was made to improve current staging and to identify those patients in the current stage II group who have an increased risk of developing recurrent disease in the future and who might benefit from adjuvant treatment. This was based on the assumption that some patients in the stage II group actually belong to the stage III groep (patients with lymph node metastases). In other words, with the current techniques of lymph node analysis some nodal metastases may be missed, leading to a false node-negative classification in some stage II patients. There are two explanations for this nodal ‘understaging’. It is possible that not enough nodes are identified from the colon specimen, leaving some positive nodes unidentified. In addition, it might be that the identified nodes are insufficiently examined, thereby missing the smaller metastases. We performed 2 studies on the subject of the number of examined nodes. First the quality of lymph node sampling in colon carcinoma in the Northern part of the Netherlands was studied. It appeared that T-stage, tumor localization and patient age were related to the number of nodes examined. In 70% of the patients less than the recommanded 12 nodes were examined. A higher number of examined nodes was associated with an increase in node-positivity. The survival benefit with more examined lymph nodes in N0 patients can be explained by stage migration. This may eventually lead to a survival benefit, as more patients will receive adjuvant therapy when more lymph node metastases can be detected. In the next chapter we evaluated the effect of a different fixation method (modified Davidson’s Fixative (mDF)) on the number of lymph nodes examined and staging in patients with colon carcinoma. With the mDF technique the median number of examined nodes increases from five to thirteen. Smaller nodes and more micrometastases (6% vs 16%) were found. The percentage of node positive patients increased from 30 to 41%, leading to more patients being eligible for adjuvant chemotherapy. The next 3 chapters report on the results of the sentinel lymph node biopsy (SLN) in colon carcinoma. Our studies show that the SLN concept in colon carcinoma using Patent Blue V is feasible and accurate. It leads to an upstaging of nodal status in 18-33 % of patients when IHC and PCR techniques are combined. It might be that these patients belong to the high risk stage II patients that we are looking for in our selection of patients for adjuvant therapy. However, long follow up results of these patients have to be awaited in order to interpretate the real significance of this upstaging. The last chapter shows the results of a review on adjuvant chemotherapy in colon carcinoma are presented, with a special focus on chemotherapy in high risk stage II patients. Since the late eighties and early nineties, 5-fluorouracil (5-FU) based chemotherapy is the standard adjuvant treatment for stage III colon cancer. In stage II patients, the role of adjuvant chemotherapy is still debatable. However, there is indirect evidence of benefit for patients with high-risk stage II disease including bowel obstruction, perforation, T4 stage and identification of less than 12 examined lymph nodes in the pathology report.