While there are good reasons to not pursue chemo after surgery for stage I NSCLC, there are several factors that argue at least for strong consideration of adjuvant chemotherapy for higher risk patients. Because stage IB generally has a less favorable prognosis than stage IA, it’s not suprising that the debate about which patients should or should not be receiving post-op chemo has centered more on the stage IB population, which have much more commonly been included in trials testing the value of adjuvant chemotherapy. Now we’ll focus on why tumor size has emerged as probably the most important factor in borderline cases where we might consider adjuvant chemotherapy but aren’t definitely convinced.
In my last post I enumerated reasons to not pursue adjuvant chemo for stage I patients, in whom the separation between T1 cancers and T2 cancers is usually the size, with a cutoff of greater or less than 3 cm (involvement if the pleural lining on the outer edge of the lung can also make a smaller tumor a T2 lesion). In that post, I described several positive adjuvant chemotherapy trials that did include stage IB patients, including the IALT trial (abstract here), Canadian BR.10 trial (abstract here), and the ANITA trial (abstract here), but in all of these cases, the stage I patients showed little or no benefit while the benefits were much greater for stage II and IIIA patients. And then there is the very important CALGB 9633 trial (preliminary 2004 abstract here, revised 2006 abstract here) that randomized over 300 patients, all with resected stage IB NSCLC, to 4 cycles of carbo/taxol or observation alone. As described in detail in my prior post, the preliminary results of the trial were positive overall, with a 12% improvement in overall survival at four years in recipients of carbo/taxol, but the curves came together and were not significantly different for overall survival (but were better for progresison-free survival) for those receiving adjuvant chemotherapy. But at the time that the revised negative results for the overall study were presented, Dr. Strauss presented an analysis of his trial outcomes that showed that the stage IB patients who had cancers of 4 cm or larger had a significant benefit from chemotherapy, while there was no benefit from the patients with tumors that were less than 4 cm:
(Click to enlarge images)
Interestingly, although this hasn’t been published yet to my knowledge, my understanding is that the BR.10 trial that showed no separation of the curves for stage IB cancers actually shows the same result, with better results for chemo recipients in the patients who had tumors of 4 cm or greater.
Intuitively, this makes sense, since the risks of chemo are the same whether you have little to gain or a lot to gain from more treatment, and we also know that the risks of recurrence and death increase as the size of the tumor increases (abstract here):
While most of us might have presumed this, it’s still helpful to see the actual data from lung cancer cases bear this out. And because of these, many experts recommend post-operative chemotherapy very rarely for people with stage I NSCLC tumors smaller than 4 cm but are much more likely to recommend it for a patient with a larger cancer.
There are a few additional factors that are worth considering for patients and oncologists weighing the pros and cons of adjuvant chemotherapy, and I’ll cover some of those extras soon. But tumor size has thus far been the most dominant factor in question of whether to pursue chemo in the stage I setting.