Histologic shift to adenocarcinomas during this time also played a role

From 2006 to 2016, deaths from non-small cell lung cancer (NSCLC) decreased, and researchers suggest that—along with a myriad of treatment advances—a diagnostic shift from later to earlier stage lung cancer and a histologic shift to adenocarcinoma are to thank. They published their results in JAMA Network Open.

“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 non–small cell lung cancer (NSCLC). This stage shift could substantially confound the evaluation of newer therapeutics and mortality outcomes,” wrote researchers led by Raja Flores, MD, of the Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York.

“To better understand the association of early detection with lung cancer mortality, it is pertinent to evaluate the extent of stage shift in the last decade and its effect in contributing to NSCLC incidence-based mortality. We hypothesize that lung cancer early detection by CT, both intentional and nonintentional (back-alley screening), such as cardiac CT angiograms screening for coronary disease, and a more attention-oriented approach to incidentally identified pulmonary nodules, is associated with a stage shift and subsequent decreased mortality from earlier surgical intervention,” they added.

Thus, using SEER registry data, Flores and colleagues identified and assessed 312,382 patients with NSCLC (median age: 68 years; 53.4% male; 12.2% Black; 79.7% White) from 2006-2016. They assessed incidence-based mortality; shifts in diagnostic characteristics, clinical stage, and histology distribution; and overall survival according to stage.

Year-of-diagnosis, noted Flores and fellow researchers, was evenly distributed, with about 9% diagnosed each year of the study. Significant associations were found between year-of-diagnosis and tumor histology (χ2: 8,990.0; P<0.001), and researchers discovered significant increases in adenocarcinoma, from 42.9% in 2006 to 59.0% in 2016 (AAPC: 3.4; 95% CI: 2.9-3.9); and in squamous cell carcinoma, from 23.7% in 2006 to 26.0% in 2016 (AAPC: 1.2; 95% CI: 1.1-1.4). They did find, however, a significant decrease in patients diagnosed with other NCSLC histologies, from 33.4% in 2006 to 14.4% in 2016 (AAPC: −8.4; 95% CI: −10.5 to −6.4).

In all, 28.2% of the sample were diagnosed at stage I/II, 69.5% at stage II/IV, and 2.3% were missing staging information. Most patients had adenocarcinoma histology (52.2%), 13.3% had a tumor size <2 cm, 26.9% tumor size ≥5 cm, and 20.3% were missing tumor size information.

Researchers found a decrease in incidence-based mortality within 5 years of diagnosis between 2006 and 2016 (AAPC: −3.7; 95% CI: −4.1 to −3.4). Upon gender-based analyses, Flores and colleagues found greater declines in the incidence of NSCLC in men compared with women. For both men and women, incidence-based mortality declined at a greater rate than the incidence. In men, the AAPC of incidence-based mortality from 2006 to 2016 was −4.2 (95% CI: −4.6 to −3.7), and for women, −3.4 (95% CI: −3.9 to −2.9).

Researchers also observed significant associations between year-of-diagnosis and clinical stage in their analysis of stage shifts. Diagnoses of stage I/II diseases increased from 26.5% to 31.2% (AAPC 1.5; 95% CI: −0.5 to 2.5), while stage III/IV diagnoses significantly decreased, from 70.8% to 66.1% (AACP: −0.6; 95% CI: −1.0 to −0.2).

Median survival was as follows for the various stages:

  • Stage I/II: 57 months.
  • Stage III/IV: 7 months.
  • Missing stage: 10 months.

Most patients missing staging information were male (51.8%) and White (77.5%), and more common in the earlier years of the study. Compared with the entire cohort, fewer patients in this group had adenocarcinoma (41.9%), squamous cell histology (26.8%), and other NSCLC histologies (31.3%). In this group, 86.7% did not undergo surgery as first-line treatment, while only 20.4% received chemotherapy, and 13.4%, external beam radiotherapy. Patients without stage information also had significantly worse survival compared with patients with stage I/II disease, and it was comparable to those with stage III and stage IV disease (log-rank χ2: 8,7125.0; P<0.001).

“Over the last decade, lung cancer population mortality has decreased. This decline has been driven by many factors, including smoking cessation, medical therapies, CT screening, and earlier therapeutic interventions,” wrote Flores and colleagues.

“Our findings in context with these prior studies seem to suggest that awareness of CT lung cancer screening is associated with an earlier detection of NSCLC (back-alley CT screening). The greater decline in incidence-based mortality compared with the incidence of NSCLC over the past decade may be partially explained by stage and histology shifts. We realize that patient adherence to lung cancer screening with low-dose CT remains limited. According to the National Cancer Institute (NCI), uptake of CT screening has been limited and stable since 2010, with 4.5% and 5.9% of adults aged 55 to 80 years in 2010 and 2015 respectively, who met the USPSTF criteria for lung cancer screening, received a CT scan within the prior year. Thus, we cannot only attribute the trends in NSCLC incidence and incidence-based mortality over the past decade to purposeful lung cancer screening with CT,” they concluded.

According to Claudia Henschke, MD, PhD, who leads one of the largest lung cancer screening programs in the U.S. at the Icahn School of Medicine at Mount Sinai, these results from Flores et al highlight the importance of ensuring screening in patients who are eligible, as well as expanding eligibility in nonsmoking patients who develop lung cancer, in whom the cancer is usually found later.

“If all people who were eligible to be screened received the low-dose CT scan, which has a dose of radiation comparable to an annual mammogram, we could save up to 80% of those people,” Henschke said in a press statement. “Our lung cancer screening program is open to all people at risk of lung cancer, anyone who is 40 and older whether they are never-smokers, current smokers or former smokers.”

Study limitations include its retrospective nature, lack of data for characteristics such as smoking status, family history, occupational exposure to carcinogens, driver variations, and diagnostic methods. Researchers also noted the number of patients who were unstaged or had no information.

  1. Population-level mortality for NSCLC decreased from 2006 to 2016, according to a large retrospective analysis of SEER data.

  2. In addition to advances in treatment, shifts in diagnoses from later to earlier stage lung cancer and a histologic shift to adenocarcinoma are also associated with this decrease in mortality.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

Flores reported no disclosures.

Cat ID: 24

Topic ID: 78,24,730,24,192,65,925