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Dr. Jack West is a medical oncologist and thoracic oncology specialist, and Executive Director of Employer Services at the City of Hope Comprehensive Cancer Center in Duarte, CA.

Balancing Risks of Undertreatment vs. Overtreatment of Locally Advanced NSCLC
Sat, 05/14/2011 - 15:48
Author
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

Our multidisciplinary thoracic oncology tumor board is dynamic and a highlight of the week, facilitated in equal parts by the fact that our group genuinely enjoys each other’s company and that it is the source of some engaging debate about the potential best way to manage several complex scenarios in lung cancer. There are a few that have become recurring debates, among them the question of whether to pursue surgery for a patient with a locally advanced NSCLC, perhaps felt to be unresectable or on the outer limits of resectability, who has undergone chemotherapy and concurrent radiation to a potentially curative dose, has encouraging but ambiguous imaging findings, and is now being considered for surgery. Essentially, this is a troubling struggle of trying to balance our concern for over-treating vs. potentially under-treating this patient.

balanced-scale

The challenge emerges out of the fact that while chemo/radiation delivered to a curative dose can on its own be curative about 20% of the time, and even comparing this strategy to one of chemo/radiation followed by surgery hasn’t shown a statistically significant improvement in survival by adding surgery. At the same time, we know we don’t have a reliable way to say that someone has had a great response to this non-surgical treatment: the first few scans are usually very ambiguous in showing some residual scarring vs. residual cancer even if the overall area of known cancer is much smaller after chemo/radiation. And while surgery is most typically done after a patient has received 45-50 Gray of radiation, (about 5 weeks), a subset of lung surgeons have become experienced and comfortable with doing lung surgery after radiation given to “full” dose RT of 60 Gy or higher (~6.5 – 8 weeks). However, it becomes technically more difficult to do this resection if more than about 6 weeks elapses between the end of radiation and the surgery.

Not surprisingly, even in the absence of clear proof that surgery will improve survival in this situation, many physicians, patients, and caregivers are inclined to pursue surgery if it can be done, on the presumption that removing any potential viable cancer is likely to be beneficial. And sometimes people undergo surgery and have residual cancer resected. In other cases, perhaps about 30% of the time or a little more, the pathology shows that there is no viable cancer, leading us to conclude that the surgery may have actually been unnecessary because they were actually likely to have been cured by the chemo/radiation already.

So we know that an arguable “standard of care” of chemo and full dose chest radiation may potentially be curative but often isn’t – yet we can’t be confident of our ability to tell the difference except with follow-up over many months or years. We can potentially do surgery, and while we would definitely prefer to wait on surgery until we can get a read on whether the risk is increased or not, that optimal window for surgery closes before we have that luxury. Instead, if we decide to pursue surgery, which is pushing the envelope compared with the textbook standard of care, we need to accept that some patients will incur the risks of the side effects of surgery, both short term and long term, potentially even death, despite a subset of them already being cured.

And so, this discussion remains a troubling one for our group, particularly in patients who have had what appears to be a good response after chemo/radiation, because they are more likely to be cured without any further interventions. We consider the health of the patient, the safety of the surgery (is it a lobectomy that would need to be done, or a more extensive and dangerous pneumonectomy?), the probability that there is residual viable cancer (we may be more risk-tolerant in someone who we feel has little to lose by trying a more aggressive approach), and of course the preferences of the patient.

While we hope to get far more information to guide us from the growing experience of more surgeons and multidisciplinary programs pursuing this approach of full-dose chemo/radiation followed by potential surgery, we’ll likely continue to have this debate about the risks of overtreatment vs. undertreatment for a long time to come. In the best case, this aggressive approach may be considered as giving a patient two shots on goal, potentially to be cured with the chemo/radiation or the surgery that follows, but I always wonder how a patient feels if they learn that they had no viable cancer in the resected tissue: relief with a level of assurance for a favorable prognosis, or perhaps regret that a big surgery may not have been needed after all?

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