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Ann Thorac Surg 2000;70:1453-1454
© 2000 The Society of Thoracic Surgeons
a Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Address reprint requests to Dr Ginsberg, Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, #C-881, New York, NY 10021
In this issue of The Annals, the Osaka group reports their experience with 91 patients undergoing pulmonary resection for small cell lung cancer (SCLC) based on the new 1997 TNM staging system [1]. These results mimic those already seen in the literature using the 1987 TNM classification. Although not conclusive, it does appear that perioperative chemotherapy, either preoperative, postoperative or both, improves survival as long as a complete course (four cycles or more) of chemotherapy is administered. The significance of this has to be the recommendation that for those patients operated upon without a diagnosis and found to have small cell lung cancer (and 
of the patients in this series are included in this group) postoperative chemotherapy is likely to improve survival despite one report to the contrary [2]. Not addressed is the question as to whether a surgical approach is appropriate for all patients preoperatively diagnosed with early stage (1 & 2) SCLC versus a primary chemoradiation approach.
Frequently, in our own experience with SCLC, needle aspiration biopsies can be inaccurate and patients with atypical carcinoid tumors are treated inappropriately with chemotherapy based on the cytology obtained from such a biopsy of a peripheral nodule. We believe that peripheral stage 1 tumors even when proven on needle biopsy to be small cell lung cancer should be offered a surgical approach since many of these will prove not to be SCLC and it does appear that the results of surgical resection for stage I disease are excellent.
In the recent report of a radiotherapy intergroup trial, chemoradiation in limited SCLC achieved a 20% 5-year survival [3]. Most of these patients probably were not the "very limited" disease [4] that surgeons operate upon (T1-2N0-1) but more advanced disease (N2,3). Unfortunately, clinical TNM staging was not used in this study. For this reason, we have no idea the cure rate in patients clinically staged T1 or 2 N0 with chemoradiation as the primary treatment. For the moment, therefore, surgery must be considered the treatment of choice in such patients. We must encourage our radiation and medical oncology colleagues to use TNM staging for limited SCLC so that in the future we can compare results.
If a diagnosis of this "very limited" SCLC is made clinically and a surgical approach is being considered, I believe mediastinoscopy is mandatory to rule out N2 disease. The results of surgery in patients with significant N2 disease whether or not they receive induction chemotherapy or postoperative chemotherapy appear no better than those seen using standard chemoradiation approaches. A Lung Cancer Study Group randomized trial confirmed this conclusion [5].
The role of salvage surgery following failure of chemoradiation with only local recurrence present is undefined but, certainly, occasional patients have been cured in this manner [6]. Reinduction of radiation or chemotherapy alone cures few if any patients with local recurrent disease. Some of these patients will have had "mixed" tumors and demonstrate persisting non-small cell disease rather than SCLC in the locally recurrent area. The authors of this paper do not mention how many patients in their series had these mixed tumors.
The greatest problem facing surgeons today is the new 1999 World Health Organization (WHO) pathologic classification for SCLC [7]. Pathologists differ in their interpretation of what this disease is. In the past, two variants of small cell lung cancer were accepted—oat cell carcinoma and intermediate cell carcinoma. Presently, pathologists define SCLC similar to that previously described as oat cell carcinoma with no intermediate cell variant but they also describe a variant of non-small cell disease termed "large cell neuroendocrine tumor", many of which would have been previously called "intermediate cell variant" and treated as such. They certainly appear to have the same very poor prognosis [8, 9]. Other pathologists insist that this is a totally different entity. Adding to the confusion is another variant called "large cell carcinoma with neuroendocrine features." This latter type is not a neuroendocrine tumor and does not stain as such but, is indeed, a non-small cell lung cancer. It is my own belief that in many cases those now diagnosed as "large cell undifferentiated neuroendocrine tumors" are indeed one of the varieties previously included in the small cell classification as "intermediate cell" variant (even though the cells are large!). If this tumor is found at the time of surgery, I believe adjuvant chemotherapy is warranted much like SCLC. Unfortunately, these are beliefs that have not as yet been verified since pathologists cannot agree on the classification! In a recent issue of The Annals, Garcia-Yuste and colleagues [9] use the classification proposed by Dresler and associates [8] which includes carcinoids, atypical carcinoids, large cell neuroendocrine and small cell tumors as a spectrum of "neuroendocrine lung tumors." This would eliminate the small cell versus non-small cell classification we have become so used to in treating our patients and change it to neuroendocrine versus nonneuroendocrine treatment groups. This has caused significant problems for the clinician. There is an urgent need to reassess the results of surgery for this newly defined subset and assess the role of chemotherapy, no matter the stage, when this subset is found. Better yet, we and our pathologists had better get together!
References
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