Nuances in Which Patients Should Receive Adjuvant Chemothera

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Nuances in Which Patients Should Receive Adjuvant Chemotherapy for Node-Negative Resected NSCLC

May 11th, 2012 - by Dr. Jack West

http://blog.lungevity.org/2012/05/11/nu ... ted-nsclc/

Last weekend, I participated in a debate on the question of whether people who had undergone a resection of a node-negative early stage non-small cell lung cancer (NSCLC) should ever be candidates for adjuvant (post-operative) chemotherapy. I had been assigned the side of there being a role for adjuvant therapy “sometimes”, as opposed to “never”. Besides the truism that always and never are very rarely the right answer in medicine (can’t say these are never the right answer), I also had been assigned an easier task because I would say that the evidence does favor the concept that there aren’t ironclad rules about which patients are better served by pursuing adjuvant chemotherapy and which ones may well do better without it.

The basic principle is this: we know that people who undergo surgery for lung cancer remain at some risk for the cancer recurring. The stage of the cancer provides a pretty good approximation of the prognosis, which is really primarily the likelihood of the cancer recurring and the patient dying from the cancer. The lower the stage (from Ia on the low end to IVb on the high end), the better the prognosis. In the world of resectable, curable NSCLC, patients who have stage II or IIIa NSCLC are the group of surgery patients who have the strongest evidence to support additional therapy after surgery, and the results are much more equivocal for patients with stage Ib NSCLC (in the slightly outdated staging system that was used in these trials, these were primarily people with a cancer larger than 3 cm or with a smaller one but pleural lining involved by tumor, and no lymph nodes involved).

Chemotherapy, typically 3-4 cycles of a platinum-based doublet combination, has been shown to reduce the risk of the cancer recurring, thereby improving survival, in higher risk patients. How much of a benefit it provides depends on how great the risk is that the cancer will recur: it is relative to the risk of recurrence. What this means is that for people with a very high risk of recurrence, like 50-75% with surgery alone, that reduction in absolute terms may be pretty substantial, in the range of a 20% reduction. In contrast, if a person has a very low risk of recurrence, such as 10% for a very small and well-behaved cancer, the absolute reduction might be more like 1-2%. In contrast, the detrimental effect of chemotherapy, in terms of both acute challenges and potential long-term risks, are the same whether someone has a more threatening or a less threatening cancer. The detrimental effects are more related to the health of the patient.

What all of this means is that whether the benefits of treatment exceed the risk for an individual patient depends on the threat of the cancer along with the fitness of the patient to tolerate chemotherapy safely. While stage captures a fair amount of the threat posed by the resected cancer, there are actually several others that are not captured. The National Comprehensive Cancer Network (NCCN), which produces the most widely used guidelines for clinical oncology practice, has noted that chemotherapy is a consideration for patients with node-negative NSCLC that is identified as higher risk not only based on size of the cancer, where a cut-off of 4 cm or greater has been the primary consideration as a threshold marking higher risk that would justify chemotherapy, but several other factors that are also correlated with higher risk of recurrence, including each of the following:

visceral pleural invasion

tumor grade (particularly poorly differentiated cancers)

vascular invasion

wedge resection

absence of lymph nodes removed during surgery

All of these have been studied and shown to be correlated with survival, even if they don’t have a clear rule for a cut-off to follow. Over the next few weeks, I’ll provided a discussion of each of these variables in more detail.

What we come away with is a sense that there are several important factors that might lead us to modify our level of concern about an individual patient, aside from surgical stage alone. The decision of whether to recommend chemotherapy ultimately emerges as a very personal discussion that includes not only a focus on the stage of the cancer, but also integration of factors such as the bulleted list noted above, the patient’s health and ability to tolerate rigorous chemotherapy safely, and their own preferences and motivation.

This was just the top level view, but I’ll cover these issues more thoroughly in upcoming posts.