Patients with non-small cell lung cancer, or NSCLC, who have preexisting COPD have shorter survival in early stages of lung cancer, according to findings of a study. Prior chronic bronchitis showed worse prognosis compared to emphysema.


 

Non-small cell lung cancer (NSCLC) and COPD rank among the leading causes of morbidity and mortality throughout the world. Previous research has suggested that COPD is a risk factor for NSCLC, and some data have shown that air flow obstruction among people with NSCLC was the most common cause of death. “A key factor that influences survival in lung cancer is selecting an appropriate course of therapy based on risk assessments,” says Shweta Shah, PhD. “However, the selection of therapy is currently based on cancer stage alone and does not consider the contribution of other factors to survival.”

Although COPD has been consistently linked to the development of lung cancer, the association between preexisting COPD and its phenotypes—chronic bronchitis and emphysema—among patients with NSCLC across different lung cancer stages is unclear. “A clearer understanding of this relationship would be useful in the early detection of NSCLC, disease progression, survival outcomes, and treatment selection in early and advanced cancer,” says Dr. Shah.

 

New Data

For a study published in the International Journal of Chronic Obstructive Pulmonary Disease, Dr. Shah and colleagues investigated the impact of preexisting COPD and its subtypes (chronic bronchitis and emphysema) on overall survival (OS) in elderly patients with different stages of NSCLC. They analyzed SEER-Medicare data on patients diagnosed with NSCLC at any disease stage between 2006 and 2010. The authors identified 66,963 patients with NSCLC, about one-third of which had documented COPD before their NSCLC diagnosis. For the COPD subtype analysis, approximately 19% of patients with lung cancer with preexisting COPD had chronic bronchitis and nearly 6% had emphysema.

For each stage of NSCLC, the study team observed marked OS differences in early-stage lung cancer. “When compared with patients with NSCLC who did not have preexisting COPD, those with preexisting COPD had marked decreases in OS from Stage I to Stage IV NSCLC,” Dr. Shah says (Table). “We also found that patients with chronic bronchitis had shorter OS at every stage of NSCLC when compared with emphysema, including Stage I and II NSCLC. After multivariable adjustment, patients in the preexisting COPD group had an 11% shorter time to death when compared with the non-COPD group.”

 

Big Implications

According to the Dr. Shah, results of the study have clinical implications for the early identification of those at greater risk of NSCLC prognosis and for those who will benefit from more optimal targeted treatment in both early and advanced stages of cancer. There is growing evidence suggesting that altered DNA methylation and chronic mucous hypersecretion in association with chronic bronchitis pathogenesis plays a role in promoting lung carcinogenesis.

“To our knowledge, our study is the first to individually assess the impact of chronic bronchitis and emphysema on the prognosis of NSCLC,” says Dr. Shah. “Our results showed that patients with pre-existing chronic bronchitis have worse survival outcomes in early stages of NSCLC (I and II) when compared with emphysema. These data are important given that clinical guidelines for NSCLC treatment provide clinicians with little guidance in caring for patients with pre-existing COPD.”

Dr. Shah notes that it can be challenging to determine who should be screened for lung cancer. “While low-dose CT is effective for early detection in high-risk patients, it is more difficult to determine which patients should be screened in the primary care setting,” Dr. Shah says. “Results from our study indicate that screening for NSCLC in patients diagnosed with prior COPD may have an excellent risk-benefit ratio for early lung cancer detection. Furthermore, COPD screening should be initiated in patients with NSCLC as early as possible to help identify mortality risks across all stages of lung cancer.”

 

More to Come

The investigators noted that future studies should validate data from the current study and seek to identify shared genetic and epigenetic risk factors and biomarkers for COPD development. “Ultimately, we want to establish target populations for chemo-prevention,” says Dr. Shah. There is also a great need for comparing and sharing data to better inform our understanding of disease progression and the impact of COPD on survival in people with NSCLC.”

References

Shah S, Blanchette CM, Coyle JC, Kowalkowski M, Arthur ST, Howden R. Survival associated with chronic obstructive pulmonary disease among SEER-Medicare beneficiaries with non-small-cell lung cancer. Int J Chron Obstruct Pulmon Dis. 2019;14:893-903. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503488/.

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