CORRESPONDENCE Minimal Survival After Chemoradiation Therapy for “Non-Bulky” Stage IIIA NSCLC: What Are the Implications? To the Editor: Cerfolio and colleagues [1] presented provocative results of surgical treatment in an important subset of stage IIIA nonsmall cell lung cancer (NSCLC) patients with clinically evident, but “non-bulky,” and potentially resectable N2 disease. I am puz- zled why the authors do not appear to trust their findings and are hesitant to explore the implications of their data. Their survival curve of 253 patients treated with chemoradia- tion alone seems to show that all patients died. The curve reaches baseline at zero just beyond 6 years. This is a startling result. Prospective, randomized series suggest that long-term survival in stage III patients treated with chemoradiation should be approximately 15%, and this study reports a highly selected, favorable prognosis subset, with “bulky” N2 patients excluded. Why did nonsurgical patients in this series die? Are they doing something wrong in Alabama? I can’t credit this possibility. The University of Alabama is an excellent comprehensive cancer center and Dr Cerfolio has a long and distinguished record of excellence in thoracic surgery. Patients received standard chemotherapy regimens and aggressive radi- ation therapy. All surgical patients had systematic mediastinal node dissection. When new results do not support old beliefs, it is time to question those assumptions. Is it possible that stage IIIA guideline recommendations based on prior multimodality treatment protocols get it wrong? I have previously com- mented that two prior prospective, neoadjuvant randomized trials showed early promise, but did not achieve statistically significant improvement with long-term follow-up [2]. An alternative hypothesis might be that neoadjuvant chemother- apy or definitive chemoradiation therapy for stage III NSCLC delay progression and recurrence, but do not cure. This hypothesis could be tested by extended follow-up of survival in prior research studies. In my opinion, the survival of Cerfolio and colleagues’ surgical patients in this report, and in his earlier series on resection of N2 disease in cN0 patients [3], in addition to data from recent publications from Riquet and colleagues [4] and Edelman and colleagues [5], prompt a critical appraisal of guideline recommendations against surgical treatment of stage IIIA NSCLC [6]. Furthermore, if resection for patients with potentially resect- able stage III disease is beneficial, is preoperative mediastinos- copy advisable or might it be causing harm by disruption of planes of surgical resection and spillage of tumor cells? If mediastinoscopy is harmful, then survival after subsequent surgery should be better in patients resected without prior N2 biopsy or after preoperative ultrasound-guided needle biopsy rather than mediastinoscopy. Because Cerfolio and colleagues’ [1] team used these two different biopsy schemas, they might answer this question by review of study data to see if survival differed with mediasti- noscopic versus ultrasound-guided endoscopic needle techniques. A final question for Dr Cerfolio is proposed: Given his large experience in resection of N2 disease, with and without prelim- inary mediastinoscopy, and with neoadjuvant therapy, can he comment on whether mediastinal node dissection is different in these groups? Does previous mediastinoscopy followed by che- motherapy and radiation therapy make it more difficult to achieve R0 resection of residual mediastinal node metastases? Frederic W. Grannis, Jr, MD Department of Thoracic Surgery City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 e-mail: fgrannis@coh.org References 1. Cerfolio RJ, Maniscalco L, Bryant AS. The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives. Ann Thorac Surg 2008;86:912–20. 2. Grannis FW Jr. Comment on Rosell et al, Roth et al, and Gandara et al. Lung Cancer 2000;28:247– 8. 3. Cerfolio RJ, Bryant AS. Survival of patients with unsuspected N2 (stage IIIA) nonsmall-cell lung cancer. Ann Thorac Surg 2008;86:362– 6. 4. Riquet M, Bagan P, Le Pimpec, et al. Completely resected non-small cell lung cancer: reconsidering prognostic value and significance of N2 metastases. Ann Thorac Surg 2007;84: 1818 –24. 5. Edelman MJ, Suntharalingam M, Burrows W, et al. Phase I/II trial of hyperfractionated radiation and chemotherapy fol- lowed by surgery in stage III lung cancer. Ann Thorac Surg 2008;86:903–11. 6. Grannis FW Jr. Is primary resection of stage IIIA lung cancer futile? Ann Thorac Surg 2008;86:353– 4. Reply To the Editor: We thank Dr Grannis [1] for his letter and for his interest in our recent article [2]. Grannis has posed several interesting ques- tions and we are happy to respond to them all. His first question is: “Why we do not appear to trust {our own} findings?” I remain unsure as to how he arrived at such a conclusion. There is no evidence that suggest a “lack of trust” that I can see, and I can assure him that we trust our data and results just fine. Perhaps it is better to state that we urge caution to anyone who reads or writes an article that is retrospective and contains data from a single institution. One should not make irresponsible sweeping conclusions. Although some may label this “mistrust,” we believe it is better labeled as “good judg- ment.” We stand by the data and the study, but as stated in the discussion section, there are important limitations to this study and thus to its conclusions. Second, Grannis asks why there were no survivors in the 253 patients who did not receive surgery but underwent chemoradio- therapy alone. Again, I am puzzled about this question as well, because I do not know where he got such a figure. As shown in Figure 2 of our article [2], there were 13 patients alive at 5 years (5% survival) and 6 alive at 6 years (2.4%), and the curve does not reach zero, so there are some projected survivors after 6 years. Moreover, Table 3 reports the survival of several nonoperative groups and none are reported as 0. Perhaps he is asking why the survival is so low in the patients that did not have surgery. This may be due to the careful and complete follow-up of the patients and also due to the fact (as described in the “Methods” section) that states that those lost to follow-up were censored. Grannis’ next question is: “Are {they} doing something wrong in Alabama?” We believe the answer is no, at least not that to which we are aware. Moreover, because many of the patients in © 2009 by The Society of Thoracic Surgeons Ann Thorac Surg 2009;87:1320 – 6 • 0003-4975/09/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2008.09.059 MISCELLANEOUS