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J Thorac Cardiovasc Surg 2003;126:1665-1666
© 2003 The American Association for Thoracic Surgery

Letters to the editor

Reply to the editor

^a Division of Thoracic Surgery and Endoscopy, Ruhrlandklinik, Essen, Germany

Reply to the Editor:

We are glad to respond to the questions of Margaritora and colleagues, as they come from a thoracic surgical group with an established experience in the multimodality treatment of lung cancer.

The results of our study show that pN1 non–small cell lung cancer (NSCLC) could not be considered an "early stage" disease, because as many as 45% of patients at the time of diagnosis and treatment had occult disease beyond the boundaries of the lobe of origin, if we consider that even a locoregional recurrence develops outside the margins of "radical" surgical resection.

Another finding is that N1 NSCLC behaves heterogeneously, with two extremes: a population of patients with hilar lymph node metastases prognostically comparable to "limited" N2 disease and, on the other side, a more favorable subgroup of cases with N1 disease by direct infiltration of pulmonary lymph nodes. This difference involves also the pattern of tumor relapse. In fact, we have observed rates of cancer recurrence of 41% at distant sites and of 12% locoregionally for the hilar N1 group and of 24% and 17%, respectively, for the N1 group by direct invasion. It is therefore our opinion that the optimal treatment of all these patients mandates multimodality approaches, which should be appropriately investigated by means of randomized clinical trials.

In the adjuvant setting, in all N1 subgroups the risk of distant metastases overwhelms that of locoregional recurrence. This evidence represents a rationale to use systemic therapy (eg, chemotherapy) after surgical resection, although the role and effectiveness of adjuvant chemotherapy in early stage NSCLC are still controversial.^1,2 Radiotherapy seems to be less mandatory, because adequate surgery is able to achieve long-term local control in as many as 85% of patients and chemotherapy may also contribute to reduce locoregional failures. Nevertheless, the cited phase III study on patients with N0 NSCLC suggests that modern radiation therapy improves local control with an acceptable toxicity.^3,4 Further randomized trials are needed to define the role of radiotherapy in N1 NSCLC. Interesting data could be obtained from the forthcoming publication of the results of the International Adjuvant Lung Cancer Trial (EORTC Trial CT0142), which in stages I to IIIA NSCLC compares different adjuvant chemotherapy regimens (cisplatin plus VP16 or cisplatin plus vinca alkaloids) against control, with radiotherapy being optional.

In the neoadjuvant setting, preoperatively scheduled chemotherapy, alone or in combination with radiotherapy, provides survival advantages in locoregionally advanced NSCLC, as shown by many clinical trials.^5-7 Phase II studies of patients with early-stage NSCLC treated with induction chemotherapy have had encouraging results, but randomized trials are needed to clarify whether a multimodality approach could protect the patients against tumor recurrence.

The main problem of designing randomized trials with neoadjuvant treatment for patients with N1 NSCLC is how to obtain an accurate lymph node staging with the available diagnostic tools. Whereas cervical mediastinoscopy is highly sensitive and specific to exclude N2 as well as N3 status, computed tomographic scan of the chest does not allow detection of lymph node metastases in the stations 10 to 14 in most cases. The simultaneous combination of positron emission tomography and computed tomographic scan, as well as endoscopic ultrasonography, could afford further information about N1 nodes but are not yet considered for routine use. We agree with Margaritora and coauthors that is difficult to achieve the histologic or cytopathologic assessment of N1 disease and that more invasive diagnostic procedures (eg, video-assisted thoracoscopy or thoracotomy) are to be considered improper for routine clinical staging. Therefore, phase III studies on neoadjuvant chemotherapy or chemoradiotherapy in early stage NSCLC could actually be designed only by excluding patients with N2 and N3 disease and enrolling patients with true N1 and true N0 disease together.

References

1. Wagner H. Postoperative adjuvant therapy for patients with resected non-small cell lung cancer: still controversial after all these years. Chest. 2000;117(4 Suppl 1):110S–118S[Abstract/Free Full Text]
   
2. Non–Small Cell Lung Cancer Collaborative Group. Chemotherapy in non–small cell lung cancer: meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ. 1995;311:899–909[Abstract/Free Full Text]
   
3. Granone P, Trodella L, Margaritora S, Cesario A, Corbo GM, Mantini G, et al. Radiotherapy versus follow-up in the treatment of pathological stage Ia and Ib non–small cell lung cancer. Early stopped analysis of a randomized controlled study. Eur J Cardiothorac Surg. 2000;18:418–424[Abstract/Free Full Text]
   
4. Trodella L, Granone P, Valente S, Valentini V, Balducci M, Mantini G, et al. Adjuvant radiotherapy in non–small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Radiother Oncol. 2002;62:11–19[Medline]
   
5. Rosell R, Gomez-Codina J, Camps C, Maestre J, Padille J, Canto A, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med. 1994;330:153–158[Abstract/Free Full Text]
   
6. Roth JA, Fossella F, Komaki R, Ryan MB, Putnam JB Jr, Lee JS, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst. 1994;86:673–680[Abstract/Free Full Text]
   
7. Eberhardt W, Wilke H, Stamatis G, Stuschke M, Harstrik A, Menker H, et al. Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non–small cell lung cancer: mature results of a phase II trial. J Clin Oncol. 1998;16:622–634[Abstract]
   

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Georgios Stamatis Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Marra, A. Articles by Stamatis, G. Search for Related Content PubMed Articles by Marra, A. Articles by Stamatis, G. Related Collections Lung - cancer Related Article