Dear Editor

We read with interest the article by Mescoli et al. on the high prevalence of isolated tumours cells in regional lymph nodes from pN0 colorectal cancer (CRC). [1] Based on a detailed study of resected lymph nodes, Mescoli et al reported that more than 50% of pN0-CRC patients have isolated tumour cells (ITC) in the mesenteric lymph nodes and ITC status significantly correlated with cancer stage and vascular cancer invasion. The existence of nodal micrometastases has been previously reported in lung and breast cancers and probably occurs with all malignancies. [2,3] Izbicki et al. in a similar study on NSCLC, reported micrometastases in 27.4% of pathological N0 and 45% of pathological N1 histological negative mediastinal nodes using more sensitive monoclonal immunostaining methods. [2] The current study further contributes to the increasing evidence that what clinicians considered as early stage cancers are probably systemic in nature by the time of diagnosis or treatment. This is important as it highlights 3 major relevant points. Firstly, with supporting studies now reporting that lymphogenesis in addition to previously known angiogenesis predicting tumour spread, it is becoming very clear how inadequate the current staging modalities are, which as yet does not take into account the presence of ITC. Secondly, all surgical tumour resection should include at least a sampling of the local regional lymph nodes in all cancers and using immunohistochemistry will provide clinicians with a more accurate system of tumour staging. The inclusion of local regional lymph nodes sampling is important and in a study by Chong et al., the inclusion of systematic mediastinal lymph nodes dissection in early clinical N0-1 NSCLC, reported the presence of pathological N2 disease in 27% of cases who were considered early NSCLC using current clinical staging methods. [4] Lastly, with the existence of ITC in local regional lymph nodes of early stage cancers, the question arises whether adjuvant chemotherapy has any beneficial role. Certainly the benefit of adjuvant chemotherapy in early stage 1B NSCLC has in recent years been proven with a reported 5% overall survival benefit. [5] Any beneficial effects of adjuvant chemotherapy in early stage cancers will certainly have to outweigh the risk of side effects associated with current chemotherapy regimens and perhaps future development of chemotherapy regimens with better safety profile and fewer or even no side effects may yet shift this balance and improve the current survival curve of early malignancies further.

Reference

1. Mescoli C, Rugge M, Pucciarelli S, et al. High prevalence of isolated tumour cells in regional lymph nodes from pN0 colorectal cancer. J Clin Pathol. 2006; 59:870-4. Epub 2006 Apr 7.
2. Izbicki JR, Passlick B, Hosch SB, et al. Mode of spread in the early phase of lymphatic metastasis in non-small cell lung cancer: significance of nodal micrometastasis. J Thorac Cardiovasc Surg 1996; 112:623-30.
3. Ku NN. Pathologic examination of sentinel lymph nodes in breast cancer. Surg Oncol Clin N Am. 1999; 8:469-79.
4. Chong CF, Leong KL, Lim TK, et al. Comparison of clinical with pathological nodal staging from systematic mediastinal lymph node dissection in early stage non-small cell lung cancer. Singapore Med J (In Press).
5. Winton T, Livingston R, Johnson D, et al; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus Cisplatin vs. Observation in Resected Non¨CSmall-Cell Lung Cancer. N Engl J Med. 2005;352:258.