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.
posted by Dr. West @ 9:22 am link to this post
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November 20th, 2006 at 6:09 pm
I had stage 1A squamous cell carcinoma also emphysema and barrett esoghagus. Even though my cancer was caught early would follow up treatment had made chances of recurrence safer?
November 21st, 2006 at 3:18 pm
Bonnie,
There is very little evidence to suggest that stage IA patients are likely to benefit from post-operative chemotherapy, or radiation for that matter. Very few of the post-op treatment trials have included them, since the prognosis is good enough that we think it’s likely that the risks of treatment, even if small to modest, may be equal to or outweigh the little benefit that treatment could provide over the already good prognosis. A “meta-analysis”, which pools results from multiple trials to try to get a signal of what each trial individually might not be able to show, suggested that there may actually be a detrimental effect of chemo (with cisplatin, which has generally been one of the key drugs used post-oepratively), compared to no further chemo.
Overall, there are still questions about stage IB NSCLC, where many of us could go either way depending on the health of the patient, the size of the tumor, etc., but I would say that the clear and probably vast majority of lung cancer experts would not recommend post-operative chemo for stage IA cancer, because the prognosis is too good without chemo to realistically improve much on that.
December 21st, 2006 at 6:58 pm
Dear Dr. West,
You answered my post on another web site, which I really appreciate, and I came to your web site to read your archives.
My husband was just diagnosed as Stage I B. He did not have any lymph node involvement, but his tumor was 4 cm. He had a lobectomy on 12/6, very successful, and after only 15 days, he is walking 2 miles a day and feeling pretty good. (He felt great before surgery, just a cough, but a CAT scan showed the questionable mass)
Now, this is the question: should a Stage I B who did not have any lymph node involvement get chemo to kill any stray cancer cells? Between the bronchoscopy, the mediascopy and the lobectomy, they tested a lot of lympn nodes, and they were all clear.
Would chemo help my husband to become one of those 15% who get a complete cure?
Thank you for you input.
December 21st, 2006 at 10:42 pm
A few points to clarify. The cure rate is considerably higher for stage I patients, more in the range of 70-75% for stage IB. The 15% is the higher end estimate of the proportion of patients for whom chemo can be the difference between being cured and not. The added benefit of chemo is likely to be smaller if the patient already has a high likelihood of cure, which is why there’s such debate about stage IB. The cure rate is already high enough that the added benefit of chemo is probably closer to 5% (and could be less).
Right now, there’s much more consensus about recommending chemo for stage II or IIIA than stage IB. There was actually an analysis of one pivotal stage IB study, the CALGB 9633 trial, in which there was a significant benefit only for tumors of 4 cm or greater, but not for smaller ones.
My general rule is that I will be inclined to recommend chemo for healthier patients with stage II and IIIA NSCLC after surgery, and for the motivated and fitter ones with larger (4 cm or greater) tumors and IB disease. It sounds like your husband fits into that category, with his excellend recovery, but I would not expect the marginal benefit of chemo to be as great as in patients with a higher risk of recurrence than he has.
December 22nd, 2006 at 5:55 am
Dr. West thank you for your response. You are so experienced and knowledgeable, but for most of us, it’s a crash course in uncharted waters. It’s very difficult for my husband and I to know how to proceed. His case is on the bubble….his tumor was exactly 4 cm. The path. report states: “bronchioloalveolar, mucinous variant and invasive acinar component.” All his lymph nodes and margins were clear. Would you get chemo if you were in his situation? He’s 66; he quit smoking 10/06 after smoking heavily for years. But, he’s a young 66…very active & robust. The side effects of chemo are frightening…One other question….how soon after surgery should the chemo start if we decide on that route. It has only been 16 days since his lobectomy. Thank you….
December 22nd, 2006 at 12:20 pm
We generally target getting chemo started somewhere in the range of 5-7 weeks after surgery. I have almost never started someone less than 4 weeks out, since people need to recover, but the studies generally start by 6-7 weeks after surgery, and a longer wait could potentially (at least theoretically) be associated with a higher risk of metastatic spread over time. I wouldn’t be very concerned if it was 7.5 or 8 weeks after surgery, but if 3-4 months go by, I wouldn’t presume that chemo would definitely have the same degree of benefit.
-Dr. West