Noncancer-specific mortality increases with age in patients with stage I NSCLC

Noncancer-specific mortality may be a competing event for lung cancer–specific mortality, particularly with increasing age, in patients who undergo curative-intent resection of stage I non–small cell lung cancer, according to a competing risks analysis.

Thus, cause-specific outcome analyses may better stratify patients with stage I than OS or EFS.

“In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors — specifically, comorbidities associated with increasing age — contribute to the risk [for] death,” Prasad S. Adusumilli, MD, FACS, deputy chief of thoracic services at Memorial Sloan Kettering Cancer Center, and colleagues wrote.

However, no comprehensive analyses have been published to include short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who underwent resection for stage I NSCLC.

Therefore, Adusumilli and colleagues performed a competing risks analysis of 5,371 consecutive patients who underwent curative-intent resection of primary lung cancer from 2000 to 2011 at Memorial Sloan Kettering Cancer Center.

A majority of the 2,186 patients with pathologic stage I NSCLC were women (59.1%), former or current smokers (84.2%), had no history of chronic obstructive pulmonary disease (75.3%) or cardiovascular disease (81.0%), had a Charlson comorbidity index of 1 or more (59.1%), were diagnosed with adenocarcinoma (79.8%) and had stage IA disease (71.0%).

More than 70% of patients (n = 1,532) were aged 65 years or older — including 29.2% (n = 638) who were aged 75 years or older. Most patients underwent lobectomy (73.7%).

Postoperative severe morbidities developed in 167 patients (7.6%), including 114 (68.3%) respiratory morbidities and 31 (18.6%) cardiovascular morbidities. Severe and respiratory morbidities were more common in those who underwent lobectomy of the lower right side.

Median follow-up was 4.2 years (range, 0.01-14.4).

Cardiorespiratory disease was the most frequent cause of death at 30 days (mortality rate, 0.7%) and 90 days (mortality rate, 1.2%).

The 1-year mortality rate was 4.1% (n = 90). Noncancer-specific mortality was the leading cause of death at 1 year (50%), followed by lung cancer–specific death (27.8%) and other cancer–specific death (13.3%).

The 5-year mortality rate was 19.9% (n = 436), which included lung cancer–specific (41.5%), noncancer-specific (22.2%) and other cancer–specific (14.4%) deaths.

Overall 5-year lung cancer–specific cumulative incidence of death was higher than noncancer-specific cumulative incidence of death (10.4% vs. 5.3%).

Lung cancer–specific cumulative incidence of death was greater than noncancer-specific cumulative incidence of death for patients aged younger than 65 years (7.5% vs. 1.8%), 65 to 74 years (10.7% vs. 4.9%) and 75 years or older (13.2% vs. 9%).

Cumulative incidence of death from noncancer-specific causes was greater for up to 1.5 years after resection, at which time lung cancer–specific causes surpassed noncancer causes. However, in patients aged 75 years or older, noncancer-specific mortality was greater for 2.5 years postsurgery.

“The higher incidence of short-term noncancer-specific mortality was enhanced in the older cohort and diminished in the younger cohort, which underscores the clinical significance of assessing noncancer-specific mortality as a competing event in older patients,” the researchers wrote.

Multivariable analysis demonstrated 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).

“Compared with the common approach of OS or EFS, cause-specific outcome analysis better stratifies patients with stage I NSCLC according to their risk for cancer morality relative to noncancer competing causes of death,” the researchers wrote. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.” – by Kristie L. Kahl

Disclosure: Adusumilli reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.