Prognostic role of minute ventilation/carbon dioxide production slope for perioperative morbidity and long-term survival in resectable patients with nonsmall-cell lung cancer: a prospective study using propensity score overlap weighting

Background: The role of minute ventilation/carbon dioxide production (V ($) over circleE/V ($) over circle CO2) slope, a ventilation efficiency marker, in predicting short-term and long-term health outcomes for patients with nonsmall-cell lung cancer (NSCLC) undergoing lung resection has not been well investigated. Material and Methods: This prospective cohort study consecutively enrolled NSCLC patients who underwent a presurgical cardiopulmonary exercise test fromNovember 2014 to December 2019. The association ofV ($) over circleE/V ($) over circle CO2 slopewith relapse-free survival (RFS), overall survival (OS), and perioperative mortality was evaluated using the Cox proportional hazards and logistic models. Covariates were adjusted using propensity score overlap weighting. The optimal cut-off point of the V ($) over circleE/V ($) over circle CO2 slope was estimated using the receiver operating characteristics curve. Internal validation was completed through bootstrap resampling. Results: A cohort of 895 patients [median age (interquartile range), 59 (13) years; 62.5% male] was followed for a median of 40 (range, 1-85) months. Throughout the study, there were 247 relapses or deaths and 156 perioperative complications. The incidence rates per 1000 person-years for relapses or deaths were 108.8 and 79.6 among patients with high and low V ($) over circleE/V ($) over circle CO2 slopes, respectively [weighted incidence rate difference per 1000 person-years, 29.21 (95% CI, 7.30-51.12)]. A V ($) over circleE/V ($) over circle CO2 slope of greater than or equal to 31 was associated with shorter RFS [hazard ratio for relapse or death, 1.38 (95% CI, 1.02-1.88), P= 0.04] and poorer OS [hazard ratio for death, 1.69 (1.15-2.48), P= 0.02] compared to a lower V ($) over circleE/V ($) over circle CO2 slope. A high V.E/V.CO2 slope increased the risk of perioperative morbidity compared with a low V ($) over circleE/V ($) over circle CO2 slope [odds ratio, 2.32 (1.54-3.49), P< 0.001]. Conclusions: In patients with operable NSCLC, a high V<($)over circle>E/V ($) over circle CO2 slope was significantly associated with elevated risks of poorer RFS, OS, and perioperative morbidity.