SCLC incidence has also decreased, but survival post-Dx is not improved

Non-small cell lung cancer (NSCLC) mortality saw a sharp decline from 2013 to 2016, which can be attributed to declining incidence as well as better survival after diagnosis. Small-cell lung cancer (SCLC), however, saw a decline in incidence, but there was no improvement in survival for those diagnosed.

Nadia Howlader, PhD, from the Surveillance Research Program, Division of Cancer Control and Population Sciences at the National Cancer Institute, Bethesda, Maryland, and colleagues, noted in The New England Journal of Medicine that the decline in NSCLC post diagnosis is likely due to improved therapies, specifically targeted therapies.

“Over the past decade, the treatment paradigm for advanced NSCLC has evolved dramatically,” Howlader and colleagues wrote. “The identification of ’druggable’ oncogenes (i.e., EGFR and ALK) has provided new, effective treatment targets, improving survival significantly among patients harboring the corresponding driver mutation. More recently, immune-based therapies — specifically, programmed cell death protein 1–programmed death ligand 1 (PD-1– PD-L1) inhibitors — have substantially improved outcomes of NSCLC treatment.”

They noted that immunotherapy with single-agent PD-1 inhibitors nivolumab, pembrolizumab, and atezolizumab showed improved survival results over single agent docetaxel in patients without EGFR and ALK mutations, with about 20% of patient having a durable response. “The approval and adoption of these agents over the past 5 to 10 years has undoubtedly contributed to the decline we observed in incidence-based mortality,” they wrote.

In contrast, the decline in SCLC mortality may be associated with decreased incidence, but “this result correlates with the limited treatment advances for SCLC over the same period. Studies have shown some promising immunotherapy strategies for the treatment of this recalcitrant disease; however, the long-term effect of these agents is unknown.”

In their study, Howlader and colleagues cited the statistics from the Annual Report to the Nation on the Status of Cancer, which showed that mortality has decreased faster than incidence for both lung and bronchus cancer — “for men, a −2.6% mean annual change in incidence from 2011 through 2015, as compared with a −4.3% mean annual change in mortality from 2012 through 2016; for women, a −1.2% mean annual change in incidence and −3.1% mean annual change in mortality during these same periods.”

But lung cancer is a catch phrase for both subtypes of cancer — NSCLC and SCLC — and progress in incidence and mortality has differed, so “to understand lung-cancer mortality trends and the effect of preventive interventions as compared with treatment interventions,” Howlader and colleagues had to assess each individual disease subtype.

In their analysis, Howlader and colleagues used data from Surveillance, Epidemiology, and End Results (SEER) Program to assess lung-cancer mortality and deaths from lung cancer linked to incidence cases in the cancer registries.

“This allowed us to evaluate population-level mortality trends attributed to specific subtypes (incidence-based mortality),” the study authors wrote. “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.”

Of note, Howlader and colleagues found that when using the Center for Health Statistics for death-certificate mortality records versus incidence-based mortality, they found a higher rate lung cancer deaths; however, this could have been “misattribution or overattribution” of deaths from lung cancer, as metastasis to the lungs is common in other cancers.

“For example, 15,866 deaths from lung cancer in the National Center for Health Statistics database did not link to a lung cancer diagnosis, instead being matched to a non–lung-cancer diagnosis in SEER,” they wrote. “Of these 15,866 deaths from lung cancer, 11,078 (approximately 70%) were linked to persons with only one primary diagnosis that was not a lung cancer diagnosis, clearly indicating misattribution. This observation suggests that mortality from lung cancer may be lower than currently reported and may be captured more accurately with the incidence-based mortality approach than with National Center for Health Statistics death certificate data.”

That said, looking at mortality trends in lung cancer and separating according to subtype and sex, they found the following:

  • NSCLC in men decreased 6.3% annually from 2013 through 2016, whereas the incidence-based mortality decreased 3.1% annually from 2008 through 2016.
  • Lung cancer–specific survival of NSCLC improved from 26% among men diagnosed in 2001 to 35% for those diagnosed in 2014.
  • The improvement in survival was found across all racial and ethnic groups.
  • NSCLC incidence in women was flat from 2001 to 2006 but decreased 1.5% annually from 2006 to 2016. Incidence-based mortality decreased by 2.3% annually from 2006 through 2014 and accelerated to 5.9% from 2014-2016.
  • SCLC in both men and women decreased similar to incidence in both sexes. “For example, among men, incidence-based mortality decreased by 4.3% annually (95% CI, 3.7 to 4.3), whereas the incidence declined by 3.6% annually (95% CI, 3.3 to 3.9),” the study authors wrote.
  • The relative survival curve for SCLC was “more or less flat, indicating a lack of improvement during this period.” Similar patterns were seen among women.

Limitations of the study included the study’s methodology of using incidence-based mortality.

  1. While non-small cell lung cancer mortality saw a sharp decline from 2013 to 2016, which can be attributed to declining incidence as well as better survival after diagnosis, small-cell lung cancer saw a decline in incidence but no improvement in survival.

  2. The decline in NSCLC post-diagnosis is likely due to the improved therapies, particularly targeted therapies.

Candace Hoffmann, Managing Editor, BreakingMED

Howlader had no disclosures.

Cat ID: 24

Topic ID: 78,24,730,24,935,192,195,65