Impact of Increasing Age on Cause-Specific Mortality and Morbidity in Patients With Stage I Non-Small-Cell Lung Cancer: A Competing Risks Analysis

Abstract

Purpose To perform competing risks analysis and determine short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who had undergone resection for stage I non-small-cell lung cancer (NSCLC). Patients and Methods Of 5,371 consecutive patients who had undergone curative-intent resection of primary lung cancer at our institution (2000 to 2011), 2,186 with pathologic stage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were included in the analysis, specifically, Charlson comorbidity index, predicted postoperative (ppo) diffusing capacity of the lung for carbon monoxide, and ppo forced expiratory volume in 1 second. Cause-specific mortality analysis was performed with competing risks analysis. Results Of 2,186 patients, 1,532 (70.1%) were ≥ 65 years of age, including 638 (29.2%) ≥ 75 years of age. In patients < 65, 65 to 74, and ≥ 75 years of age, 5-year lung cancer-specific cumulative incidence of death (CID) was 7.5%, 10.7%, and 13.2%, respectively (overall, 10.4%); noncancer-specific CID was 1.8%, 4.9%, and 9.0%, respectively (overall, 5.3%). In patients ≥ 65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer-specific CID; the higher noncancer-specific, early-phase mortality was enhanced in patients ≥ 75 years of age than in those 65 to 74 years of age. Multivariable analysis showed that low ppo diffusing capacity of lung for carbon monoxide was an independent predictor of severe morbidity ( P < .001), 1-year mortality ( P < .001), and noncancer-specific mortality ( P < .001), whereas low ppo forced expiratory volume in 1 second was an independent predictor of lung cancer-specific mortality ( P = .002). Conclusion In patients who undergo curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with an increasing impact as patient age increases.

Fig 1.

CONSORT diagram. The study cohort included all consecutive patients who underwent R0 resection for pathologic stage I non–small-cell lung cancer (NSCLC). R0, microscopically margin-negative resection.

Fig 2.

Lung cancer–specific and noncancer-specific 5-year cumulative incidence of death (CID) by age-group. (A) Up to approximately 1.5 years after surgery, noncancer-specific CID was higher than lung cancer–specific CID. After 1.5 years, lung cancer–specific CID surpassed noncancer-specific CID (N = 2,186). (B) The higher noncancer-specific CID observed in the early postoperative phase increased in patients ≥ 75 years of age, in whom noncancer-specific mortality was higher than lung cancer–specific mortality until approximately 2.5 years postsurgery (n = 638). (C) In patients 65 to 74 years of age, the difference between curves was similar to that for the total cohort (n = 894). (D) In patients < 65 years of age, lung cancer–specific mortality was higher than noncancer-specific mortality during most of the postoperative period (n = 654).

Fig 3.

Estimated 5-year lung cancer–specific and noncancer-specific Charlson Comorbidity index (CCI). The mean for each variable was summarized and fitted by using cubic B-splines for graphic representation. Along the x-axis, each group interval was represented as the middle number, such as 55 for 51-60 in panel A. (A) Lung cancer–specific cumulative incidence of death (CID) is highest (approximately 15%) at the lowest predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) and decreases linearly as ppo FEV1 increases. Noncancer-specific CID plateaus when ppo FEV1 is ≥ 65% (61%-70%) but increases precipitously as ppo FEV1 decreases below that point. (B) Lung cancer–specific CID gradually decreases as ppo diffusing capacity of lung for carbon monoxide (DLCO) increases, but the gradient is more gradual than that for ppo FEV1. By contrast, noncancer-specific CID decreases linearly from approximately 11%-1% as ppo DLCO increases. (C) Noncancer-specific and lung cancer–specific CID increase as CCI increases from 0 to 1 but essentially plateaus when CCI increases to > 1.