Ann Thorac Surg 2003;76:1864-1865
© 2003 The Society of Thoracic Surgeons
Invited commentary
Cameron Wright, MD
Massachusetts General Hospital, Blake 1570, 55 Fruit St, Boston, MA 02114, USA
e-mail: wright.cameron{at}mgh.harvard.edu
Doctors Kondo and Monden have organized a large contemporary database to see if the TNM staging system would fit thymic epithelial tumors. After a careful review of their data I believe the answer to be no for thymoma and maybe for thymic carcinoma. A staging system is valuable to estimate prognosis, decide on therapy and to compare results. Most would agree that simplicity and clinical validity are the two cardinal features of a successful staging system. Unnecessary subdivisions of tumor characteristics result in survival curves that do not separate well (and hence reduce the statistical difference between groups of patients) and make the system needlessly complex and difficult to remember. Clinical validity relates to the most important tumor variables (proven prognostic factors derived from large high quality databases utilizing multivariate analysis) for that specific tumor. For example, in soft tissue sarcoma, the histologic grade of the tumor is by far the most important prognostic variable while the lymph node status is not really relevant. The art of designing and comparing tumor staging schemes is complex and not standardized. A recent paper examining this problem in detail using thymoma as a model is worth reviewing to understand the uncertainties even our biostatistician colleagues have in this very complex area [1].
Less than 2% of patients with thymomas have nodal metastases. Only 1% of patients with thymoma have distant metastases. The rarity of this biologic behavior indicates that the N factor would not be a good candidate for stratifying survival in a staging system. This is emphasized by the p value in the multivariate analysis indicating a modification of the Masaoka system (stage 1, 2 vs 3, 4) was far superior (p < 0.001) to nodal metastases (p < 0.053) for predicting survival. While the Masaoka staging system is widely used, most agree it could be improved upon as there is no difference between stage 1 and 2 in almost all modern reports, stage 3 is heterogeneous and the new WHO histologic grading system is not used (most reports indicate the histologic type of thymoma stratifies survival, as well as the Masaoka stage, and is independently predictive of survival). I do not think the TNM system would be appropriate for thymoma given the information in this report.
In thymic carcinoma lymph node metastases are relatively common (27% of cases) and there is a difference in survival between node negative and positive patients. This finding is confirmed in multivariate analysis and is the only tumor factor predictive of survival. As in other recent reports, the Masaoka staging system (which was formulated only for thymoma, not thymic carcinoma) was not independently predictive of survival in thymic carcinoma. The stratification of the different lymph groups was not fully significantly different and seems needlessly complex to me. It would seem more reasonable, in the absence of more data to just call intrathoracic nodes positive or negative. Extrathoracic nodes are essentially distant metastatic disease (and actually have a worse prognosis than M1 disease comparing Figures 3b and 4b) and should not be labeled as N3. This report supports the concept of using nodal status as a valid discriminator of prognosis in thymic carcinoma. The next step in formulating a TNM type system for thymic carcinoma would be to identify a tumor factor (such as size, depth of invasion, number of involved organs) that would independently stratify survival.
References
- Begg C.B., Cramer L.D., Venkatraman E.S., Rosai J. Comparing tumor staging and grading systems: a case study and a review of the issues, using thymoma as a model. Statist Med 2000;19:1997-2014.
