Screening for Lung Cancer in Never-Smokers 'Feasible'

Liam Davenport

February 02, 2021

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

"Lung cancer in never-smokers is a global rising threat," said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

Crucially, the incidence of lung cancer ― in particular, adenocarcinoma ― is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the recent World Conference on Lung Cancer (WCLC) 2020, Yang presented new results which show that "LDCT screening for never-smokers with high risk may be feasible."

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55 to 70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease, passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0–I in 95% of cases.

Interestingly, the lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.

Interesting; More Research Needed

The TALENT study "provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia," commented the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan, Italy.

However, he said that "more research is needed on lung cancer biology in nonsmokers."

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, DC, said that although family history "emerges" from the study as a potential risk factor for lung cancer, "this analysis would be much more insightful with genomic analyses of these cancers."

https://twitter.com/StephenVLiu/status/1355294055870193665?s=20

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, commented that the study is "interesting," given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a "robust" study of the biology of lung cancer in this population.

https://twitter.com/DevikaDasMD/status/1355296210924544001?s=20

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said that the study "provides new evidence" on lung cancer risks.

"As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope," she said.

https://twitter.com/ProjectBreath/status/1355297667350335490?s=20

Details of TALENT Findings

The TALENT study recruited individuals aged 55 to 70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

  • Family history of lung cancer in up to third degree relatives, in which case younger patients could be recruited

  • Environmental (passive) tobacco smoking history

  • Chronic lung disease, namely, tuberculosis or chronic obstructive pulmonary disease

  • A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking

  • Cooking without ventilation

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules >6 mm in diameter or pure ground-glass nodules >5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled; of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2%. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Yang said that LDCT results were were positive for 17.4% of patients; 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%); of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were of stage 0–I; the majority were of stage IA, "which is higher than in other studies that have focused on heavy smokers," Yang commented. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient's relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Eli Lilly, Roche, Merck, GSK, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma and Lin BioScience. Pastorino has disclosed no relevant financial relationships.

World Conference on Lung Cancer (WCLC) 2020: Abstract PS01.02. Presented January 30, 2021.

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