Lung cancer screening in patients with COPD ‘is complex’
Key takeaways:
- There is uncertainty surrounding the link between COPD and lung cancer.
- Selecting patients who should undergo lung cancer screening is challenging in the presence of COPD.
PHILADELPHIA — Performing spirometry in patients with COPD before lung cancer screening could help identify those who would benefit most from screening, according to a presentation at the 2024 GOLD COPD International Conference.
“[Lung cancer] is the most common cause of cancer death throughout the world, with an estimated 1.8 million individuals dying from lung cancer in 2022, and by 2040, an estimated 2.5 million people succumbing to this disease,” M. Patricia Rivera, MD, the C. Jane David and C. Robert Davis Distinguished Professor in pulmonary medicine, chief of the division of pulmonary diseases and critical care medicine and associate director of diversity and inclusion at the Wilmot Cancer Institute at University of Rochester Medical Center, said during her presentation.
As Healio previously reported, research presented at ESMO Congress revealed a substantial overlap between patients with COPD and patients referred to undergo lung cancer diagnostics.
When thinking about causes of lung cancer, Rivera, also co-director of the North Carolina Lung Screening Registry, said the most common one is tobacco smoking, but individuals also may develop lung cancer due to radon exposure, asbestos exposure, silica exposure, family history, history of prior cancer or an underlying lung disease.
Among patients with COPD, studies have found that the risk for lung cancer is elevated in the presence of smoking, Rivera said.
“Individuals who smoke and have COPD are reported to have a sixfold increase incidence of lung cancer compared to individuals who smoke and do not have evidence of obstructive lung disease,” Rivera said.
Rivera also highlighted paraseptal emphysema as a risk factor for lung cancer but noted some “conflicting data” on the factor.
“There are studies that have shown that while airflow obstruction is associated with an increased risk of lung cancer, paraseptal emphysema actually reduces the risk,” Rivera said.
Patients with obstruction and worsening obstruction have been shown to face a heightened risk for lung cancer, but Rivera followed this up by noting there are also data suggesting a potential benefit of the COPD inflammatory environment.
“COPD is associated with a poor prognosis in lung cancer, but interestingly, COPD with inflammatory component or inflammatory environment may result in better [response] to immunotherapy in patients with lung cancer treated with these drugs,” Rivera said.
At the present, there is uncertainty surrounding the link between COPD and lung cancer, and Rivera said this may be due to great reliance on self-reported data, emphysema reported by radiologists and spirometry when studying the diseases.
“We know that these results can have reporting biases, observer error, as well as operator error, so it’s been really difficult to get to the bottom of the link between these two diseases,” Rivera said.
Notably, epithelial mesenchymal transformation, chronic inflammation, oxidative stress and DNA damage are pathogenic mechanisms involved in both COPD and lung cancer, according to Rivera.
“In patients with COPD, there is chronic, ongoing inflammation typically in lower airways, and this chronic inflammatory response leads to increased cytokine release, which then recruit and turn on neutrophils, macrophages as well as B and T lymphocytes,” Rivera said.
“This chronic, ongoing inflammatory process is a pro-tumor inflammatory microenvironment that leads to DNA damage, genetic mutations and then the downstream effects resulting in tumor formation.”
Reflecting on lung cancer screening, Rivera noted that factors for determining eligibility — age and total pack-years — are possibly “very simplistic” and suggested use of risk-based strategies.
“Using risk assessment may be very helpful in that it allows us to select high risk, high benefit individuals, so that the efficiency of screening is improved,” Rivera said. “You have to do less low-dose CTs to prevent one cancer death.”
Rivera outlined that these individuals could include current smokers, low-intensity current smokers and former smokers who quit at least 15 years ago.
Importantly, “when you use risk assessment, you’re always at the risk of identifying older individuals, as well as individuals with more comorbidities,” Rivera said.
As Healio previously reported, patients with COPD often have other diseases/conditions in addition to the lung disease, including pulmonary hypertension, type 2 diabetes and osteoporosis.
“COPD is a double-edged sword when we think about lung cancer screening,” Rivera said. “Again, these patients are at increased risk for lung cancer, but they’re also at increased risk of significant comorbidities and the risk of dying from other diseases rather than lung cancer.
“Screening patients with advanced COPD is complex,” Rivera added.
To demonstrate this point, Rivera shared findings from a study published in Thorax in 2023 that included 18,463 individuals from the National Lung Screening Trial. Pre-bronchodilator spirometry was taken before screening to group individuals by GOLD grade. Compared with individuals with non-COPD, GOLD 1 or GOLD 2, the prevalence of non-lung cancer deaths was significantly higher in individuals with GOLD 3 to 4.
With this finding and the idea that COPD may negatively impact the typical gains obtained with lung cancer screening in mind, Rivera said performing spirometry before an individual gets screened “may be very helpful.”
“We may be able to identify individuals with very mild disease and airflow obstruction who are at increased risk for lung cancer, and also perhaps identify individuals who have very severe obstructive lung disease who may not likely benefit from lung cancer screening,” Rivera said.