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Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)

 

What I Really Do: Potentially Resectable Stage IIIA NSCLC
Author
Howard (Jack) West, MD

I've covered stage IIIA NSCLC in several prior posts, mentioning that it's a clinical setting that is among the most controversial, but I don't think I've really described my real world approach. To review, the controversy is that for stage IIIA NSCLC with mediastinal lymph node involvement on the same side as the tumor (N2 nodes), some people would recommend surgery as a main treatment strategy, and others would recommend chemo and radiation without surgery. The trials that have directly compared a surgical to a non-surgical approach have shown no significant survival benefit for either approach. However, one key study demonstrated that patients who underwent surgery had a lower risk of a recurrence of lung cancer, but this was largely offset by a higher risk of treatment complications and even death related to the more aggressive treatment of chemo and radiation followed by surgery (see prior post).

There is also the question for people who are planned to undergo surgery of whether they should start with surgery or receive "induction"/neo-adjuvant therapy beforehand. And if they receive induction therapy, should it be with chemo alone or chemo and radiation together? The typical standard is that for patients who have mediastinal node involvement identified before planned surgery, we usually give chemo with or without radiation as well before surgery. You could make the argument that it's just as good to give it afterward, but stage III NSCLC is a setting in which the risk of recurrence with surgery alone is very high, and I'd feel far more optimistic about getting in chemo +/- radiation as well as surgery by starting with induction therapy and following with surgery, rather than starting with surgery and hoping to get additional therapy post-operatively. Too many patients can't or won't take more treatment after a big lung surgery to really expect that you can deliver it in the adjuvant (post-operative) setting.

There is some evidence that the patients who have bulkier cancer that would require a whole lung to be removed do better with a non-surgical approach, while the patients with less bulky disease may do better with surgery. This isn't perfect data, but it is my preference to pursue a surgical approach for patients with less bulky (<2-3 cm) mediastinal disease, and with just a single lymph node area involved in the mediastinum (midchest). There is really no good evidence to tell us whether to give chemo alone or chemo and radiation before planned surgery (see prior post), but if a patient is healthy enough, I generally recommend pre-operative chemo and radiation together. The best studied chemo approach with concurrent is a cisplatin-based combination like cisplatin/etoposide, and there really isn't any standard combination for pre-operative chemo alone. Of note, I do recommend for patients with very minimal nodal disease or who are more frail and not inclined to pursue chemo/radiation all followed surgery.

One issue that isn't very controversial is that for patients with stage IIIA disease and N2 node involvement, it's important to know whether they have any evidence of residual mediastinal node involvement after induction therapy, whether it's chemo alone or chemo and radiation (see prior post). I and my colleagues at my own institution prioritize doing a mediastinoscopy to determine whether there the mediastinum has been sterilized (cleared of all evidence of disease in the nodes) before proceding with surgery. The evidence strongly suggests that the patients who have no evidence of any residual mediastinal disease do far better after surgery than the ones who continue to have disease involvement: for the latter we generally don't recommend continuing with surgery and instead tend to favor continuing with a chemo/radiation approach, which may or may not be more effective than surgery, but it's probably going to be easier for a patient to get through.

Beyond that, there's the question of what treatment to recommend after surgery. There's essentially no evidence to help us here, but we may try to pursue another couple of cycles of chemo after surgery. In truth, these decisions are very individualized based on how effective the pre-operative treatment was, how much disease was present at the time of surgery, how the patient is doing after surgery, and how motivated they are to continue with treatment vs. stop.

One final point is that I don't generally recommend surgery for patients who are anticipated to need a pneumonectomy (removal of an entire lung), more frail patients, or those with multiple areas of mediastinal lymph node involvement and/or very bulky mediastinal disease. As noted above, I don't recommend surgery for patients who continue to have lymph node involvement after induction therapy. But it's important to remember that we definitely see patients with bulky stage IIIA and IIIB NSCLC who are cured with chemo and radiation alone, and that the cure rates with a non-surgical approach are in the same ballpark as the results with surgery for patients of the same stage. So chemo/radiation isn't an awful consolation prize.

That said, I do think that healthier patients with less bulky stage IIIA NSCLC may be better served by an aggressive approach of induction chemo, potentially also with radiation, followed by surgery, and even potentially more treatment after that. It's a lot for a patient to get through, but it's certainly worth it if it delivers a cure.

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