# Residual Volume and Total Lung Capacity at Diagnosis Predict Overall Survival in Non‐Small Cell Lung Cancer Patients

## TL;DR

Higher residual volume to total lung capacity ratio at diagnosis is linked to worse survival in non-small cell lung cancer patients, regardless of cancer stage or spirometry results.

## Contribution

Identifies RV/TLC as a novel prognostic factor in NSCLC beyond traditional spirometry measures.

## Key findings

- Higher RV/TLC ratio is associated with increased mortality risk in NSCLC patients.
- Lung volume measurements provide prognostic information beyond standard spirometry.
- RV/TLC shows significant association with overall survival after covariate adjustment.

## Abstract

Residual volume (RV) / total lung capacity (TLC) ratio has been found to better predict functional impairments than spirometry and is associated with mortality in chronic obstructive pulmonary disease; however, it is rarely studied in lung cancer. Our previous work established spirometry as a prognostic factor for lung cancer, and we aimed to further investigate the prognostic value of TLC and RV in lung cancer patients.

We identified newly diagnosed non‐small cell lung cancer (NSCLC) patients who underwent static lung function tests prior to any cancer therapy between 1992 and 2020 in a longitudinal cohort of lung cancer patients: the Boston Lung Cancer Study. Cox proportional‐hazards model was used to estimate the association between each lung volume test with overall survival.

Among 2348 NSCLC patients, 57.2% were diagnosed at stage I and 63.8% underwent surgery, with 1352 deaths observed over a median survival of 66.9 months. Higher RV, RV%, and lower TLC, TLC% were associated with worse overall survival marginally; RV/TLC was associated with overall survival as a quantitative trait, with one standard deviation (11.24%) increase in RV/TLC associated with 19.2% higher risk of mortality (HR = 1.192 [95% CI: 1.114, 1.277]) after covariate adjustment. Statistically significant interactions were found between RV/TLC and spirometry, and higher mortality risks were found with higher RV/TLC in patients across spirometry status and cancer stages.

NSCLC patients with higher RV/TLC ratios at diagnosis had worse overall survival, even when spirometry was within the predicted range. These findings suggest that lung volume measurements provide prognostic information beyond standard spirometry, supporting the need for further mechanistic and interventional studies to determine their clinical utility.

Lung volume as a part of pulmonary function test is often underrepresented in prognostic lung cancer research. In this longitudinal lung cancer patient cohort, higher residual volume to total lung capacity (RV/TLC) ratio upon diagnosis was associated with worse overall survival regardless of spirometry results or cancer stage. The findings provide first‐line evidence for the prognostic value of lung volume measurements and lay the groundwork for future studies to clarify their role in lung cancer prognosis.