This year’s annual release of cancer statistics generated more buzz than usual. Perhaps the most publicized finding in the Cancer Facts & Figures 2020 report was the 2.2% decline in overall cancer deaths from 2016 to 2017, the last year for which we have final statistics. That was the largest ever single-year drop in cancer deaths. Improvement in lung cancer — which accounts for more deaths than breast, prostate, and colorectal cancers combined — was credited with driving the decline.
It wasn’t entirely clear what accounted for the improvement. Of course, tobacco control has been an important contributor: The reduction in smoking in the U.S. has been associated with a large decrease in lung cancer deaths, beginning around 1990 in men and around 2000 in women. But the recent decline in these deaths struck many of us involved in cancer research as being too fast to be explained solely by tobacco control.
An important statistic that deserves more attention is the pattern of declines in new cases of cancer (known as cancer incidence), and its comparison with declines in cancer-related deaths. Another report on cancer statistics, the Annual Report to the Nation on the Status of Cancer, has indicated that death rates for men and women with lung cancer have been declining even faster than its incidence since about 2011. We are seeing a similar pattern for melanoma: Mortality is declining rapidly, while incidence has been flat to increasing.
What has uncoupled mortality and incidence for these two important cancers?
To better understand these patterns, researchers at the National Cancer Institute worked with collaborators at other institutions to take a deep dive into lung cancer incidence and mortality, examining patterns across the two major subtypes of lung cancer. Their findings, published this week in the New England Journal of Medicine, suggest that decades of biomedical research in cancer are paying off — and in a big way.
For this analysis, researchers compared incidence and mortality from non-small cell lung cancer (NSCLC), which accounts for 76% of lung cancers in the U.S., and small cell lung cancer (SCLC), which accounts for 13%. Though they affect the same organ, they are different types of cancer. Both are mainly caused by smoking, although a significant fraction of NSCLC occurs in nonsmokers.
In recent years, the researchers found, deaths from non-small cell lung cancer have decreased much more quickly than new cases, whereas small-cell lung cancer deaths have decreased at about the same rate as incidence.
If declining tobacco use was responsible for all of the improvements in these types of cancer, we might expect two things to be true: Declines in deaths would parallel declines in incidence, and declines would be consistent across different cancer subtypes that are caused by smoking. Since that isn’t the pattern we are seeing, something in addition to tobacco control must be at play.
It is possible that screening — testing people without symptoms to see if they might have hidden lung cancer — is detecting NSCLC at earlier stages, when it is more treatable. However, only a small portion of lung cancer diagnoses in the U.S. currently result from screening.
My colleagues and I at the National Cancer Institute believe that advances in the treatment of non-small cell lung cancer are responsible for a substantial portion of the recent declines in lung cancer mortality.
In the last decade, older therapies like surgery, radiation, and chemotherapy for non-small cell lung cancer have improved, and many new treatments for this disease have become available. These include small molecule inhibitors that target genetic changes seen in some NSCLC tumors, and immune checkpoint inhibitors that help the immune system better attack these tumors. In contrast, there have been only minimal treatment advancements for small cell lung cancer over the last 30 years.
Similar improvements in therapy for melanoma may explain why mortality is dropping faster than incidence for that cancer as well.
Even better, we can expect further declines in deaths due to non-small cell lung cancer in the years ahead. Immune checkpoint inhibitors are quite effective in some patients with NSCLC, but they came into widespread use for the disease only recently, so national mortality figures, using data through 2016, don’t fully reflect their positive impact. Continued efforts to reduce tobacco use will likely also yield further declines in lung cancer incidence and mortality.
Increased uptake of screening, which is currently underused, can further reduce deaths from lung cancer. Current guidelines recommend annual screening for adults aged 55 to 80 years who have a 30-pack-year smoking history and currently smoke or have quit smoking within the past 15 years. Those recommendations are currently being revisited, to potentially include more current and former smokers.
At the start of my career as an oncologist, advanced melanoma and lung cancer were mostly a death sentence, and there seemed to be little hope on the horizon. That we now see treatments effective enough to shift national death trends in these cancers is worth celebrating. At the same time, analyses like these point us toward vital work that remains: We still have little to offer people diagnosed with small cell lung cancer, and the treatments we have for non-small cell lung cancer aren’t right for everyone with it.
Nevertheless, the progress made in NSCLC illustrates what is possible, even for a cancer that has long had a poor prognosis for most patients. It turns out that what we can achieve is better than many of us imagined even a decade ago.
The national investment in cancer research has made possible painstaking work spanning basic science, translational research, and clinical trials. These efforts are being translated into better diagnosis and treatment, which in turn produce more years of life for people diagnosed with cancer. That’s why we’re working to make sure that encouraging trends continue.
Norman E. Sharpless is an oncologist and director of the National Cancer Institute.