One of the things we learn when studying the clinical research in lung cancer is that "global studies" often include patients with locally advanced (stage III) NSCLC along with those who have advanced (stage IV) NSCLC. Part of the confusion has been the ungainly status of stage IIIB NSCLC with a malignant pleural effusion -- historically termed "wet IIIB disease" -- in the IIIB camp but not having the curability of patients with "dry IIIB disease" --unresectable locally advanced NSCLC without a malignant pleural effusion. But while North American (at least US) trials over the past 10-15 years that are meant for patients with incurable advanced NSCLC have nearly always included only patients with wet stage IIIB disease (now moved to stage IV in the newest and most accurate lung cancer staging system) and stage IV NSCLC, trials done in other parts of the world, and especially in Europe, have often allowed patients with unresectable dry stage III NSCLC to be included as well. In their trials, patients with stage III NSCLC typically comprise only about 10-15% of the overall trial population, but I must confess that I've gone from just shrugging my shoulders and saying to myself, "I guess that's how they do it", to a perspective where I'm more inclined to articulate that this is inappropriate and objectionable, for two reasons.

The first is a relatively minor one, and that is that it makes it hard to compare results from one trial to another. The experts always say that you can't really compare results across different trials, because the people enrolled on different trials and subtle differences in the practices of the participating doctors/centers may present clinically relevant differences. There is good reason to believe this when comparing trials from US-based cooperative groups to global trials, since the latter may include a minority of patients with a better prognosis because of the more liberal eligibility requirements. So outcomes may be different, and survival may well be better, in global or European trials simply because the patient population is adulterated with participants who would be deemed to have too good a prognosis for the US-based trials.

The bigger issue, however, is that this practice consigns potentially curable patients to substandard treatment that would not be considered as potentially curative: it's essentially giving up the opportunity to cure a population that has long odds but could feasibly have a chance to be cured with multimodality treatment -- most commonly chemo and radiation, often concurrently -- by including only a systemic therapy. There may be some extenuating reasons to say that a few of these patients are not curable, but 10% of the patients on global trials is too many patients to presume that none of them could actually be cured. And while you might say that some couldn't tolerate concurrent chemo and radiation, radiation tends to be the most well tolerated modality of therapy; these patients would almost certainly still be candidates for potentially curative sequential chemo and radiation, even if they couldn't receive the most aggressive concurrent multimodality approach.

I don't mean to suggest that US-based trials all represent the pinnacle of great trial design. There have been times when I have felt as if the US-based system of getting trials completed, and the lack of American patients to accept being randomized or receive placebos, leaves us dependent on studies outside of the US to learn far too much. But I do think that the practice of undertreating potentially curable patients with locally advanced NSCLC simply because the system in which they're being treated simply accepts this injustice is unacceptable. As often as possible, I think the trials that allow this should be called out and not accepted by the better medical journals, because having them published in our more respected journals will only perpetuate this practice. I think it's time to say that it's time to give every potentially curable patient with lung cancer their best opportunity.