Ann Thorac Surg 2003;76:201-202
© 2003 The Society of Thoracic Surgeons
Original article: general thoracic
Invited commentary
Paul E. Van Schil, PhD
Department of Thoracic and Vascular Surgery, University Hospital of Antwerp, B-2650 Edegem (Antwerp), Belgium
e-mail: paul.van.schil{at}uza.be
Current TNM staging is purely anatomical and has its limitations. Even stage I patients do not have an excellent prognosis after complete resection, and approximately 25% will develop distant metastases within 5 years, which are probably already present at the time of resection. In this multicenter study, the prognostic value of cytokeratin-positive (CK+) cells as markers of micrometastases was studied. Bone marrow aspirates obtained immediately before surgical resection and lymph nodes of patients with resected nonsmall cell lung cancer were examined, the latter from stage I patients (pN0). This excellent study with a detailed analysis of long-term survival confirms the reports from other groups working on the same subject.
A striking difference between bone marrow and lymph nodes was found. Almost 32% of patients had CK+ cells in their bone marrow with no difference between pathological stages. There was a tendency to shorter survival in CK+ patients, but in stage I no difference in survival was observed. Therefore, the mere presence of these cells in the bone marrow does not always indicate a poor prognosis. Does this mean that they have less metastatic potential than those found in higher stages? What is the possible influence of the patients own immune defence on these cells? Will any treatment in these CK+ patients influence prognosis? Further research is necessary to answer these questions.
On the other hand, the presence of CK+ cells was detected in 15.7% of lymph nodes in stage I patients (pN0), which was an independent prognostic factor in a multivariate analysis. This means that once metastatic cells invade lymph nodes the prognosis becomes poor even when routine histological examination shows these nodes to be pN0. What are the precise therapeutic implications of these findings? Is there a possible role for adjuvant chemotherapy in CK+ patients? Could we enlarge our indications for induction chemotherapy when mediastinal lymph nodes biopsied at mediastinoscopy contain CK+ cells? How will the response be determined? These will be difficult questions to answer as they require well-designed large multicenter randomized trials.
The authors have shown nicely that CK+ cells in the lymph nodes have a definite prognostic value and that anatomical staging alone is not sufficient to determine ultimate prognosis. Detection of micrometastases is one intriguing way to improve our staging system. How this will influence our treatment strategies and the ultimate prognosis of our patients remains to be determined, however.
