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Division of Cardiothoracic Surgery, University of Alabama at Birmingham, 702 19th St S, Birmingham, AL 35294
(Email: rcerfolio{at}uab.edu).
We thank Dr Grannis [1] for his letter and for his interest in our recent article [2]. Grannis has posed several interesting questions 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 judgment." 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 chemoradiotherapy 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 this study who did not receive surgery had their chemoradiotherapy delivered in many other states beside Alabama, it would have to be a problem that extended outside of our state's limits. As he acknowledges this explanation seems unlikely. We attribute the low rate of survival to the proactive follow-up in our study (ie, actively following-up with patients using computed tomography and searching records as described in the "Methods" section of our article [2]). This type of proactive follow-up is quite different from that used in many large studies that implement cancer registries such as Surveillance Epidemiology and End Results, which reflects passive follow-up data of survival (eg, data reported by physicians or family members).
The next question centers on the guidelines for the treatment of stage IIIA from N2 disease. We agree that this is a very controversial issue. Because N2 disease concerns such a heterogeneous group of patients, only very carefully designed studies with strict staging tests and entry criteria are needed to fully and accurately define meaningful guidelines.
Grannis asks if mediastinoscopy is potentially "harmful by disrupting the planes of surgical resection and spilling tumor cells?" This is an interesting question, but I am not aware of any data that shows that those with N2 disease proven by mediastinoscopy have done worse or have higher local recurrence or lower overall survival than those with N2 disease proven by endoscopic ultrasound and fine needle aspiration or endobronchial ultrasound. We examined our own data and found no significant difference in this study.
He next asks about the technical exercise of removing N2 nodes after induction therapy. The dissection of N2 disease after mediastinoscopy, followed by induction chemoradiotherapy can be very difficult, especially in the lower right paratracheal lymph node (4R) region. If a patient has a right upper lobe tumor, we always ligate the right superior pulmonary vein first, then the anterior apical trunk of the right upper pulmonary artery branch second, and we finish removing the right upper lobe. Then we remove all of the N2 nodes that are often plastered to the pericardium, the trachea, and the superior vena cava. But we remove them all in their entirety. This has to be performed. It can be done safely even after a mediastinoscopy and even after a 2-month to 3-month delay while the patient is getting concurrent chemoradiotherapy up to 72 Gy. The removal of the lobe first affords more room to safely accomplish this mandatory task. Sometimes, but rarely, the azygous vein has to be ligated to help facilitate this important part of the resection. The goal is to remove all of these nodes as well as all of the other N2 lymph nodes. But it is more difficult after a mediastinoscopy than after a endoscopic ultrasound and fine needle aspiration or endobronchial ultrasound.
In conclusion, I greatly appreciate the Grannis' letters and his interest in N2 disease. We are aware of the American College of Chest Physicians' guidelines on the role of surgery for those with biopsy-proven N2 disease. However, we remain resolute that there is an important and meaningful role for surgical resection in properly selected patients with a subset of N2 disease. I believe that in this regard, Grannis and I agree because he himself states in his previous letter in The Annals of Thoracic Surgery in 2008 [3] that: "Primary surgical resection of carefully selected cases of N2 [nonsmall cell lung cancer] NSCLC is not futile and ‘thought leaders’ must stop saying that it is."
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