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Pulmonary Function at Time of Lung Cancer Diagnosis Has Prognostic Value

Key findings

  • This study examined the role of spirometry in predicting the long-term overall survival of 2,805 patients at the time of diagnosis with non–small-cell lung cancer
  • Forced expiratory volume in one second (FEV1), percent predicted FEV1, forced vital capacity (FVC), and percent predicted FVC were all associated with overall survival in a dose-dependent manner, even after adjustment for other prognostic factors
  • Spirometry-determined chronic obstructive pulmonary disease (COPD) and more advanced stages of COPD at lung cancer diagnosis were associated with worse lung cancer survival
  • Spirometry should be routine when a patient is diagnosed with lung cancer, regardless of stage, for risk stratification that can inform clinical decision-making

Preoperative spirometry has been shown to predict postoperative mortality in patients with lung cancer, but its association with long-term survival is inconclusive. Most studies have been conducted on small populations.

Ting Zhai, of the Harvard T.H. Chan School of Public Health, David C. Christiani, MD, MPH, director of the Christiani Lab in the Division of Pulmonary and Critical Care Medicine at Massachusetts General Hospital, and colleagues recently reviewed data on 2,805 adults with newly diagnosed lung cancer who participated in the Boston Lung Cancer Study at Mass General starting in 1992.

They state in Cancer Medicine that poorer pulmonary function test (PFT) results at diagnosis were associated with overall worse survival and may therefore be suitable prognostic biomarkers.

Methods

The study participants included in this analysis had non–small-cell lung cancer (NSCLC), had follow-up through at least July 2020, and had at least one PFT performed before they started lung cancer treatment. The PFTs of interest were forced expiratory volume in one second (FEV1), percent predicted FEV1 (FEV1%), forced vital capacity (FVC), and percent predicted FVC (FVC%).

Chronic obstructive pulmonary disease (COPD) was diagnosed if FEV1 and FVC was <70%. Using the 2020 GOLD criteria, COPD was staged as 1, 2, 3, or 4 if FEV1% was ≥80%, 50%–79%, 30%–49%, or <30%, respectively.

Overall Results

Pre-bronchodilator raw values of FEV1 and FVC were associated with overall survival but not in a dose-dependent manner because of the impacts of outliers. However, after categorizing the PFT values, in univariate models and compared with the highest quartile (75%–100%), the lower quartiles of FEV1, FEV1%, FVC, and FVC% were significantly associated with higher mortality. There was a "dose-dependent" relationship (i.e., larger PFT values were tied to better survival).

The associations remained true after adjustment for age, sex, body mass index, smoking status, clinical stage, and lung cancer treatment and were stratified on NSCLC histological subtypes.

To validate the associations, the researchers re-analyzed the data using post-bronchodilator spirometry results available on 43.5% of the cohort. Those showed similar dose–response relationships as the pre-treatment tests.

COPD-related Results

Among 1,275 patients diagnosed with COPD, median lung cancer survival was 76 months. More advanced stages predicted poorer survival: for stages 1 to 4, median survival was 69 months, 59 months, 38 months, and 30 months, respectively.

The risk of mortality was significantly higher in stages 2 to 4:

  • Stage 1—HR, 1.08 (95% CI, 0.92–1.27)
  • Stage 2—HR, 1.30 (95% CI, 1.15–1.46)
  • Stage 3—HR, 1.79 (95% CI, 1.53–2.09)
  • Stage 4—HR, 2.26 (95% CI, 1.59–3.22)

Advice for Clinicians

Spirometry should be routine when a patient is diagnosed with lung cancer, regardless of stage, for risk stratification that will inform decisions about treatment and care. Spirometry may particularly benefit patients in advanced disease stages since more personalized treatment might more markedly improve their survival.

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