Trends in Population-Level Stage Shift and Mortality Among U.S. Patients With NSCLC: 2006–2016

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In a retrospective cohort study reported in JAMA Network Open, Raja Flores, MD, and colleagues found that a population-level shift to earlier-stage diagnosis has been accompanied by a reduction in population-level mortality during recent years in U.S. patients with non–small cell lung cancer (NSCLC).

Raja Flores, MD

Raja Flores, MD

As stated by the investigators, “Early detection by computed tomography and a more attention-oriented approach to incidentally identified pulmonary nodules in the last decade has led to population stage shift for NSCLC. This stage shift could substantially confound the evaluation of newer therapeutics and mortality outcomes.”

Study Details

The study used data from the Surveillance, Epidemiology, and End Results (SEER) registries to assess all patients with NSCLC from 2006 to 2016. Incidence-based mortality was evaluated by year of death. Trends in mortality and stage distribution were evaluated using average annual percentage change.

Key Findings

The total population consisted of 312,382 patients, with the number of diagnoses ranging from 27,883 to 28,887 over the study years. At diagnosis, 88,179 had stage I/II disease, 217,037 had stage III/IV disease, and 7,166 had missing stage. Median age was 68 years (interquartile range [IQR] = 60–76 years), 53.4% were male, 79.7% were White and 12.2% were Black, and 52.3% had adenocarcinoma histology. 

Incidence-based mortality within 5 years of diagnosis decreased from 2006 to 2016, with an average annual percentage change of −3.7 (95% confidence interval [CI] = −4.1 to −3.4). Average annual percentage changes were −4.2 (95% CI = −4.6 to −3.7) among male patients and −3.4 (95% CI = −3.9 to −2.9) among female patients.

The proportions of all diagnoses increased from 26.5% to 31.2% (average annual percentage change [AAPC] = 1.5, 95% CI = 0.5–2.5) for stage I/II disease and decreased from 70.8% to 66.1% (AAPC = −0.6, 95% CI = −1.0 to −0.2) for stage III/IV disease. No significant change over time was observed for missing stage (2.8% in 2006, 1.7% in 2015; AAPC = −1.6, 95% CI = −7.4 to 4.5).

Year of diagnosis was significantly associated with tumor histology (P < .001); the proportion of cases with adenocarcinoma histology increased from 42.9% in 2006 to 59.0% in 2016 (AAPC = 3.4, 95% CI = 2.9–3.9).

Among all patients, median follow-up was 61 months (IQR = 21–95 months). Median overall survival was 57 months (IQR = 18 months–not reached) among patients diagnosed with stage I/II disease, 12 months (IQR = 4–34 months) for those with stage III disease, 5 months (IQR = 1–13 months) for those with stage IV disease, and 10 months (IQR = 2–28 months) for those with missing stage.

Patients with stage I/II disease had significantly better survival vs those with stage III/IV or missing stage (P < .001). Survival duration for those without stage information was between that of patients with stage III and patients with stage IV disease.

The investigators concluded, “This cohort study found that population-level mortality for NSCLC has decreased from 2006 to 2016. Although advances in treatments, particularly targeted therapeutics, have played a role in affecting mortality, our analysis suggests that decreased mortality is also associated with a diagnostic shift from later- to earlier-stage lung cancer and a histology shift to adenocarcinoma. Studies investigating the population impact of treatment on lung cancer mortality must take into account the confounding association of stage shift with survival and mortality outcome.”

Dr. Flores, of the Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, is the corresponding author for the JAMA Network Open article.

Disclosure: For full disclosures of the study authors, visit

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