The Effect of Advances in Lung-Cancer Treatment on Population Mortality

Abstract

Background: Lung cancer is made up of distinct subtypes, including non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information.

Methods: Using data from Surveillance, Epidemiology, and End Results (SEER) areas, we assessed lung-cancer mortality and linked deaths from lung cancer to incident cases in SEER cancer registries. This allowed us to evaluate population-level mortality trends attributed to specific subtypes (incidence-based mortality). We also evaluated lung-cancer incidence and survival according to cancer subtype, sex, and calendar year. Joinpoint software was used to assess changes in incidence and trends in incidence-based mortality.

Results: 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. In contrast, 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 time frame we examined.

Conclusions: Population-level mortality from NSCLC in the United States fell sharply from 2013 to 2016, and survival after diagnosis improved substantially. Our analysis suggests that a reduction in incidence along with treatment advances - particularly approvals for and use of targeted therapies - is likely to explain the reduction in mortality observed during this period.

Figure 1.. Mortality Estimates Based on Data from Death Certificates and on Incidence among Patients with Lung or Bronchus Cancer.

Shown are the estimates of mortality from lung and bronchus cancer based on data from death certificates (blue line) and the corresponding estimates of mortality based on incidence (red line). In the area to the left of the vertical line at calendar year 2006, the incidence-based mortality underestimates mortality from lung cancer. Results are shown for the Surveillance, Epidemiology, and End Results (SEER) 18-registry database, which includes the following registries: San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, Atlanta, San Jose–Monterey, Los Angeles, Alaska Native, Rural Georgia, California (excluding San Francisco, San Jose–Monterey, and Los Angeles), Kentucky, Louisiana, New Jersey, and Georgia (excluding Atlanta and Rural Georgia). For both measures of mortality, attribution to lung-cancer death is made when the cause of death on the death certificate is stated as lung and bronchus cancer (International Classification of Diseases, 10th Revision, code C34).

Figure 2.. Comparison of Mortality Estimates Based on Data from Death Certificates and on Two Measures of Incidence among Patients with Lung or Bronchus Cancer.

Shown are the estimates of mortality from lung and bronchus cancer determined on the basis of data from death certificates (blue line) and the corresponding incidence-based mortality from lung or bronchus cancer that was linked to patients with a diagnosis of lung cancer (solid red line) or to patients with any cancer diagnosis (i.e., not limited to a lung-cancer diagnosis) (dashed red line). Mortality from lung cancer may be more accurately represented with the incidence-based approach than with the approach based on death-certificate data. Results are shown for the SEER 18-registry database.

Figure 3.. Non–Small-Cell Lung-Cancer (NSCLC) Incidence, Incidence-Based Mortality, and Survival Trends among Men and Women.

Panel A shows age-adjusted incidence (blue) and incidence-based mortality (red) for the NSCLC histologic subtype among men and women. Incidence was adjusted for reporting delays. The line segments of each curve were selected with the Joinpoint program, and the percentage associated with each line represents the annual percentage change during the indicated range of years. Asterisks indicate annual percentage changes that are significantly different from zero (P<0.05). The dashed vertical line indicates calendar year 2013, when epidermal growth factor receptor (EGFR)–directed first-line therapy was approved by the Food and Drug Administration (FDA). For each incidence-based mortality curve, an arrow indicates the point at which there is a change in slope for mortality corresponding with the timing of routine testing for molecular alterations in EGFR and FDA approval for targeted therapy. Panel B shows 2-year lung-cancer–specific survival according to year of NSCLC diagnosis among men and women. Results are shown for the SEER 18-registry database. The following International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3), histology codes were used to define the NSCLC subtype — squamous and transitional cell: 8051, 8052, 8070–8076, 8078, 8083, 8084, 8090, 8094, 8120, and 8123; adenocarcinoma: 8015, 8050, 8140, 8141, 8143–8145, 8147, 8190, 8201, 8211, 8250–8255, 8260, 8290, 8310, 8320, 8323, 8333, 8401, 8440, 8470, 8471, 8480, 8481, 8490, 8503, 8507, 8550, 8570–8572, 8574, and 8576; large cell: 8012–8014, 8021, 8034, and 8082; non–small-cell carcinoma, not otherwise specified: 8046; and other specified carcinomas: 8003, 8004, 8022, 8030, 8031–8033, 8035, 8200, 8240, 8241, 8243–8246, 8249, 8430, 8525, 8560, 8562, and 8575.

Figure 4.. NSCLC Survival Trends among Men and Women According to Race and Ethnic Group.

Results for 2-year lung-cancer–specific survival are shown for the NSCLC subtype according to race and ethnic group among men (Panel A) and women (Panel B). Results are shown for the SEER 18-registry database, excluding data from the Alaska Native registry.

Figure 5.. Small-Cell Lung-Cancer (SCLC) Incidence, Incidence-Based Mortality, and Survival Trends among Men and Women.

Panel A shows age-adjusted incidence (blue) and incidence-based mortality (red) for the SCLC subtype among men and women. Incidence was adjusted for reporting delays. The line segments of each curve were selected with the Joinpoint program, and the percentage associated with each line represents the annual percentage change during the indicated range of years. Asterisks indicate annual percentage changes that are significantly different from zero (P<0.05). Panel B shows 2-year lung-cancer–specific survival according to year of SCLC diagnosis among men and women. Results are shown for the SEER 18-registry database. The following ICD-O-3 histology codes were used to define the SCLC subtype: 8002 and 8041–8045.