The cornerstone of treating early NSCLC (stage I, II, and sometimes stage IIIA) is surgery, at least if a patient is able to tolerate that. While many patients can be cured after surgery alone, patients remain at risk for both local recurrence near where the original cancer was, and also distant spread. The latter is caused by micrometastases, circulating tumor cells that cannot be detected on scans or blood tests at this time, that can grow to produce visible disease recurrence months or years after surgery. Unfortunately, we can’t detect who has micrometastases and who doesn’t, so we don’t know who is still at risk and who is cured.

So with a risk of circulating tumor cells, the treatment approach that we hope would be helpful is chemotherapy, which also circulates throughout the body to potentially eradicate any stray tumor cells that may remain after surgery. Early studies of chemo after surgery, known as adjuvant chemotherapy, were too small, and the earlier chemo approaches not quite effective enough, to show significant reductions in the risk of NSCLC recurring after surgery. Putting the results of a large number of these trials together in what is called a meta-analysis (pooling trials with similar design to see if all of them put together gives a clear signal of the effect) showed an approximately 13% lower risk of lung cancer returning. But the effect of chemo was not clear enough, and still with too many side effects, that this was not considered the standard thing to do.

Over the last several years, however, multiple larger trials with more current chemo demonstrated a statistically significant reduction in risk of the NSCLC returning after surgery. The first was published in the New England Journal of Medicine (known as the IALT trial) and considered to be a potential new standard of care. However, the improvement only translated to a 4% higher chance of being alive at 5 years after surgery if you took chemo after surgery. At the same time, the chemo used had significant side effects, and only approximately 2/3 of patients could get through most or all of the planned chemo. So many patients and oncologists felt that the results were not clinically significant enough, even if statistically significant. Some additional trials over the last 3 years have confirmed the benefit of chemo after surgery, and importantly have shown a greater degree of benefit. One, also recently published in the New England Journal by Winton and colleagues (BR.10 trial abstract), showed an improvement in 5-year survival of as much as 15%. Others showed a survival benefit at 5-years after surgery somewhere between 4% and 15%. This isn’t for every patient, as some patients have such a low risk of recurrence that the potential benefit of chemo is minimal, but the risks of chemo are no lower. Also potentially important is the fact that the median age of the adjuvant chemo trials is in the range of 59-62, which is much lower than the median age of NSCLC in the US (now over 70 at diagnosis). For many patients, risks of kidney damage, hearing loss, nausea/vomiting, and other anticipated side effects make it a questionable or perhaps poor choice, but it is often worth discussing. Other posts will cover the considerations of which chemo to use after surgery, which stages of patients are most likely to benefit, and the question of whether pre-operative chemo (also known as neoadjuvant chemo) might be an equal or better choice for patients.