We all know now that lung cancer, and in particular NSCLC, sits atop the list of cancer killers in the United States and western world. We also have been having extensive discussions on this site about all these great new treatment modalities: better staging (i.e. PET), better surgeries (i.e. VATS), radiosurgery (i.e. gamma knife), better radiation (i.e. IMRT), and better chemotherapy or targeted agents. But have all of these advancements done anything other than raise the cost of healthcare so much that Medicare is in danger of going broke paying for $100,000 Avastin-containing regimens?
In this month’s Journal of Thoracic Oncology, a group of cancer epidemiologists published a study looking at the survival of almost 11,000 patients with lung cancer over the 20 year period from 1985 to 2004, looking at the contributions of surgery, radiation, and chemotherapy and how the survival changed over that period. All of the patients were treated in Manitoba, Canada, so they can be considered to have received standard treatment for the time period and I think these patients can be compared to lung cancer patients anywhere in the developed world.
The first thing that jumped out from this study was that the rate of patients receiving surgery fell over time. Most people don’t realize that CT scans were not widely available in the early to mid-1980s, so many patients with metastatic (incurable) disease were going to the operating room when their chest x-rays incorrectly suggested they had curable disease. It makes perfect sense that fewer patients are having inappropriate surgery these days, now that staging is better in the CT and more recently the PET era.
The next interesting thing from this study, and the main point of this post, was that the authors found that overall survival in all NSCLC patients began to improve starting in 1997, and has been increasing by about 2 weeks every year between 1997 and 2004. Added together, this is about 3.5 months in improved survival over this period.
Not only did survival improve overall, it improved for early-stage patients receiving primary surgery, for locally advanced (stage III) patients getting chemotherapy and radiation, and for incurable patients treated with chemotherapy alone. The improvement in surgery is almost certainly because the staging has improved dramatically, so that only true early stage patients are getting surgery these days. Put another way, when large numbers of more advanced patients receive surgery but are not cured (because surgery does not cure stage 3 and 4 NSCLC by itself), the overall group looks like it has poor survival. So by only doing the surgery in the right patients, the overall group ends up having better survival.
The improvement in locally advanced and metastatic NSCLC survival also makes sense. Again, I doubt most people realize this today, but until 1995 there was no real evidence that chemotherapy helped anyone live longer with NSCLC. In 1995, a large meta-analysis of prior trials showed that platinum-based chemotherapy regimens did have an impact in lung cancer survival, and modern chemo began to be used much more often.
So many of you may be thinking that 3.5 months doesn’t seem like a big deal, but I would argue that it is a big deal. Keeping in mind that the average survival for patients with advanced lung cancer in 1997 was about 9 months, this represents a 39% improvement in survival in only 7 years!
I think one of the most encouraging things about this study is that this improvement in survival took place before the treatments that I mentioned above: before extensive use of IMRT or radiosurgery, before the common usage of targeted agents like Avastin or Tarceva, even before the common use of adjuvant chemotherapy after surgery, which began in 2004 and clearly is improving survival in early stage patients. I think there is a good chance that our most recent advances may actually be advancing the survival of patients at an even faster rate than described in this study.
I know that everyone secretly hopes for a dramatic cure of lung cancer. When new studies come out that show a 5 week or 2 month improvement in survival, there can be a collective yawn from the world at large. But I would argue that this is how it really works in the world of oncology, in incremental little advancements that build up over time. Colon cancer used to have an average survival very similar to lung cancer, but over 10-12 years the survival has more than doubled with the addition of several incremental advancements, each only adding 2-4 months but together helping move average survival from 10 months in the 1990s to >24 months today. It is my hope that NSCLC is well on its way!
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Posted on April 18, 2009 at 9:49 am
Though I don’t think that our desire for a dramatic cure is secret at all, I do agree that many developments that add a modest but real benefit of 1-4 months can amount to a very meaningful improvement when added together. It was only 10-12 years ago that the debates in the oncology community were about whether there was value in treating metastatic lung cancer at all, and now not only first line but second and third line therapies are increasingly established. And as real as out improvements are in median survival, I think the most impressive difference is that we now see so many more survivors two years or further out that we can clearly see a minority of patients doing far better than they did just a few years ago.
That’s in the advanced disease setting, and in the curative disease setting we now see more people living 5 years and likely cured of their disease. The establishment of post-operative chemo for early stage, resected NSCLC has improved long-term survival by 5-10% in this population. Not enough to be haughty, but a true blessing if you are one of the beneficiaries. Locally advanced disease has also been associated with an improvement in median survival from about 14 months 8-10 years ago to 20-24 months in many of the more recent trials, and the widespread use of chest radiation and concurrent radiation doubled the long term survival. While that change has been from about 10% to 20%, and not the higher numbers we’d love to see, it’s still a meaningful step.
I strongly suspect that we’ll add incrementally yet again in the next 5 years by learning more about how to optimize the exact treatment to offer based on more precise clinical and molecular profiling.
One of our remaining tasks is to improve results in small cell lung cancer, for which our treatments in 2009 are remarkably similar to those from 10 or more years ago. That hasn’t been for a lack of trying to improve our approaches, but SCLC has been a very hard nut to crack. Of course, we still have hope that amrubicin, picoplatin, and other investigational approaches can ultimately break our streak.
-Dr. West