A significant reduction in mortality from lung cancer in the US general population, mainly due to a rapid decline in mortality from non-small cell lung cancer (NSCLC) was reported on 13 August 2020 in The New England Journal of Medicine by Dr. Nadia Howlader of the Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute in Bethesda, MD, USA and colleagues. Population level mortality from NSCLC in the US fell sharply from 2013 to 2016, along with substantial improvement of survival after diagnosis. The analysis suggests that a reduction in incidence along with the treatment advances, in particular approval and use of targeted therapies during the study period is likely to explain the reduction in mortality observed.
The authors wrote in the study background that is important to assess trends in mortality from lung cancer according to subtype because the potential adoption of lung cancer screening coupled with reductions in smoking are likely to influence future mortality from lung cancer differentially according to histologic subtype.
Major improvements have been made in last years in NSCLC treatment with introduction in the practice of targeted therapies and immunotherapies. However, treatment for small cell lung cancer (SCLC) has shown limited improvements in efficacy in same timeframe.
To understand lung cancer mortality trends and the effect of preventive interventions as compared with treatment interventions, it is important to assess the individual contributions of NSCLC and SCLC to overall lung cancer incidence and mortality trends. Overall, mortality from lung cancer has been decreasing among men and women. However, this overall trend cannot be separated directly into subtype specific trends, because death certificates in the US do not record the cancer subtype.
To address this data limitation, the US Surveillance, Epidemiology, and End Results (SEER) Program has linked mortality records to incident cancer cases. In particular, the study team applied the incidence-based mortality method to SEER data to evaluate population level US mortality trends, according to sex, attributable to NSCLC and SCLC from 2001 through 2016. Since mortality captures the combined effects of lung cancer incidence and survival after diagnosis, they also assessed the contributions of lung cancer incidence and lung cancer specific survival to these trends. They also evaluated lung cancer incidence and survival according to cancer subtype, sex, and calendar year.
The study team found that mortality from NSCLC decreased even faster than the incidence of this subtype, and this decrease was associated with a substantial improvement in survival over time that corresponded to the timing of approval of targeted therapy.
Among men, incidence-based mortality from NSCLC decreased 6.3% annually from 2013 through 2016, whereas the incidence decreased 3.1% annually from 2008 through 2016. Corresponding lung cancer specific survival improved from 26% among men with NSCLC that was diagnosed in 2001 to 35% among those in whom it was diagnosed in 2014. This improvement in survival was found across all races and ethnic groups. Similar patterns were found among women with NSCLC.
However, mortality from SCLC declined almost entirely as a result of declining incidence, with no improvement in survival. This result correlates with limited treatment advances for SCLC in the timeframe of this study.
The authors concluded that they found a significant reduction in mortality from lung cancer in the US general population, mainly due to a rapid decline in mortality from NSCLC. They explained that the faster decreases in mortality from NSCLC as compared with the incidence of NSCLC are probably driven by improvements in survival, which are potentially driven by dissemination of targeted therapies for NSCLC. The survival benefit for patients with NSCLC treated with targeted therapy has been shown in clinical trials, but this study highlights their possible effect at the population level. The authors anticipate that incidence-based mortality methods will be valuable for evaluating trends in subtype specific mortality in the future, as additional new lung cancer treatments, as well as screening are penetrated in the population.
Howlader N, Forjaz G, Mooradian MJ, et al. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med 2020;383:640-9.