Diagnosis of Respiratory Sarcopenia for Stratifying Postoperative Risk in Non–Small Cell Lung Cancer

Importance: Physical biomarkers for stratifying patients with lung cancer into subtypes suggestive of outcomes are underexplored. Objective: To investigate the clinical utility of respiratory sarcopenia for optimizing postoperative risk stratification in patients with non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This retrospective cohort study reviewed consecutive patients undergoing lobectomy and mediastinal lymph node dissection for NSCLC at 2 institutions in Tokyo, Japan, between 2009 and 2018. Eligible patients underwent electronic computed tomography image analysis. Follow-up began at the date of surgery and continued until death, the last contact, or March 2022. Data analysis was performed from April 2022 to March 2023. Main Outcomes and Measures: Respiratory sarcopenia was identified by poor respiratory strength (peak expiratory flow rate) and was confirmed by a low pectoralis muscle index (PMI; pectoralis muscle area/body mass index). Patients with poor peak expiratory flow rate but normal PMI received a diagnosis of pre-respiratory sarcopenia. Short-term and long-term postoperative outcomes were compared among patients with a normal status, pre-respiratory sarcopenia, and respiratory sarcopenia. Group differences were analyzed using the Kruskal-Wallis test and Pearson χ2 test for continuous and categorical data, respectively. Survival differences were compared using the log-rank test. Univariable and multivariable analyses were conducted using the Cox proportional hazards model. Results: Of a total of 1016 patients, 806 (497 men [61.7%]; median [IQR] age, 69 [64-76] years) were eligible for electronic computed tomography image analysis. The median (IQR) duration of follow-up for survival was 5.2 (3.6-6.4) years. Respiratory strength was more closely correlated with PMI than pectoralis muscle radiodensity (Pearson r2, 0.58 vs 0.29). Respiratory strength and PMI declined with aging simultaneously (both P for trend < .001). Pre-respiratory sarcopenia was present in 177 patients (22.0%), and respiratory sarcopenia was present in 130 patients (16.1%). The risk of postoperative complications escalated from 82 patients (16.4%) with normal status to 39 patients (22.0%) with pre-respiratory sarcopenia to 39 patients (30.0%) with respiratory sarcopenia (P for trend < .001), as did the risk of delayed recovery after surgery (P for trend < .001). Compared with patients with normal status or pre-respiratory sarcopenia, patients with respiratory sarcopenia exhibited worse 5-year overall survival (438 patients [87.2%] vs 133 patients [72.9%] vs 85 patients [62.5%]; P for trend < .001). Multivariable analysis identified respiratory sarcopenia as a factor independently associated with increased risk of mortality (hazard ratio, 1.83; 95% CI, 1.15-2.89; P = .01) after adjustment for sex, age, smoking status, performance status, chronic heart disease, forced expiratory volume in 1 second, diffusing capacity for carbon monoxide, C-reactive protein, albumin, carcinoembryonic antigen, histology, and pathologic stage. Conclusions and Relevance: This study identified individuals at higher risk of poor outcomes by screening and staging respiratory sarcopenia. The early diagnosis of respiratory sarcopenia could optimize management strategies and facilitate longitudinal care in patients with NSCLC.