Dr. Rachel Sanborn, Providence Thoracic Oncology Program, discusses the reasons behind using adjuvant chemotherapy for early stage NSCLC  patients.  Clinical studies have shown that adding chemotherapy after surgery for lung cancer can indeed improve survival. 

Adjuvant Chemotherapy for Early Stage NSCLC Patients

(Part 1)

Rachel Sanborn, MD, Medical Oncologist and Co-Director,

Providence Thoracic Oncology Program

TRANSCRIPT

Although the most important part of a curative approach for lung cancer, if at all possible, is having a lung cancer removed with surgery, even in the best of situations, a patient still has a risk of the cancer coming back. The reason is that even despite the best technology that we have, microscopic cancer seeds may have spread in the body and have not been detectable at the time of surgery which, if left there untreated will grow and show up later. When that happens, although a cancer may be treatable at that time, the lung cancer in general would no longer be curable. So that’s why we consider adding chemotherapy immediately after surgery, if a person has an early stage lung cancer removed, trying to kill off those microscopic tumor deposits and trying to improve the chance of cure at that time.

There have been multiple clinical studies that have shown that adding chemotherapy after surgery for lung cancer can indeed improve survival, although the majority of this evidence is for people who have had larger tumors, tumors with more lymph node involvement. The dilemma comes more when we think about what do we do to try to help a person with an earlier stage cancer, a smaller tumor that does not have the lymph nodes involved. That’s where the data gets a little more difficult to interpret.

There have been previous studies that looked at different types of chemotherapy, one of those, a CALGB trial, looked at carboplatin with taxol and included people who had stage I lung cancers. That trial eventually was negative, which means that no benefit was seen. However, when they looked back over time at the people that received chemotherapy in that study, what was shown was that, for people who had lung cancers that were at least four centimeters in size or greater, those people may have had a benefit from chemotherapy.

There was a different study run by the NCI Canada that looked at cisplatin with a different chemotherapy called navelbine that evaluated this chemo after surgery. What was shown in that study was that people did indeed have a benefit, but when that trial looked back over time, the benefit was in people who had lymph node involvement, and those people who did not, those people with stage I lung cancers, did not get a benefit from chemotherapy. So we have conflicting data.

There was a very large meta-analysis done, called the LACE meta-analysis, that evaluated more than 4500 people in different clinical trials getting adjuvant chemotherapy. In that study, what they saw was that for people with the smallest lung cancers, those with stage Ia lung cancer, meaning three centimeters or smaller in size at the time, there was actually a trend toward harm getting chemotherapy, whereas people with slightly bigger stage I lung cancers, stage Ib, may have had a benefit but it was not significant. So in that group of people, the question was still open. It did confirm that for people with lymph node involvement of their cancers, there was indeed a benefit with chemotherapy. Again, we’re stuck in a gray zone with slightly larger tumors, but there is concern that for those people with the smallest lung cancers, the risk of the chemotherapy itself becomes higher than the benefit a person could get. That’s the reason why the next versions of adjuvant clinical trials only allowed for people who had lung cancers at least four centimeters in size.

In general, when I think about adding adjuvant chemotherapy for an early stage lung cancer, then I would consider that for a person who has a lung cancer four centimeters or greater but not smaller than that. In general, the considerations to discuss, or the considerations to evaluate, would be to make sure that a person has recovered very well after the surgery, that they have a good overall health status, that they’re able to be up and active through their day. What we want to do is make sure that the risks of toxicity are as low as they possibly can be, but we also have a long and very frank discussion about the fact that chemotherapy can be considered in those situations, but there is not the same proof of survival benefit as there is in larger tumors, that there’s not the same proof of survival benefit as there is in cancers that have lymph node involvement. So it’s important to have a very informed discussion with the patients who are considering adjuvant chemotherapy in that setting.