The observation that women with lung cancer seem to live longer than men can be explained by known prognostic factors, a new study suggests.

“In this first Australian prospective study of lung cancer survival comparing men and women, we found that men had a 43% greater risk of dying from their lung cancer than women,” comments lead author Xue Qin Yu, PhD, the Daffodil Centre, the University of Sydney, Australia, and colleagues.

“[However], when all prognostic factors were considered together, most of the survival differential disappeared,” they add.

“These results suggest that sex differences in lung cancer survival can be largely explained by known prognostic factors,” Yu and colleagues emphasize.

The study was published in the May issue of the Journal of Thoracic Oncology.

The ‘45 and Up’ Study

The findings come from the Sax Institute’s 45 and Up Study, an ongoing trial involving over 267,000 participants aged 45 years and older living in New South Wales, Australia. Patients were recruited to the study between 2006 and 2009. At the time of recruitment, patients were cancer free.

A total of 1130 participants were diagnosed with having lung cancer during follow-up — 488 women and 642 men. Compared with men, women were, on average, younger at the time of diagnosis, had fewer comorbidities, and were more likely to be never-smokers or to have been exposed to passive smoke.

Women were also more likely to be diagnosed with adenocarcinoma than men and to receive surgery within 6 months of their diagnosis.

“Lung cancer survival was significantly higher for women,” the authors report, at a median of 1.28 years versus 0.77 years for men (P < .0001).

Within each subgroup of major prognostic factors — histologic subtype, cancer stage, cancer treatment, and smoking status — women again survived significantly longer than men.

Interestingly, the authors note that “women with adenocarcinoma had significantly better survival than men with adenocarcinoma independent of smoking status,” (P = .0009). This suggests that sex differences in tumor biology may play a role in explaining the sex survival differential between men and women, they commented. That said, never-smokers had a 16% lower risk for lung cancer death than ever-smokers after adjusting for age, the authors point out.

The authors also note that approximately half of the disparity in survival between the sexes could be explained by differences in the receipt of anticancer therapy within 6 months of the diagnosis. “This could partly be due to a lower proportion of men having surgery within 6 months than women,” investigators speculate, at 17% vs 25%, respectively.

Men were also older than women at the time of diagnosis, were less likely to be never-smokers, and had more comorbidities, all of which might also have prevented them from having surgery. Women with lung cancer may also respond better to chemotherapy than men, although the sex disparity in survival persisted even among patients who did not receive any treatment for their cancer within 6 months of their diagnosis, investigators point out.

Furthermore, “smoking history at baseline was identified as a significant contributing factor to the sex survival disparity, explaining approximately 28% of the overall disparity,” Yu and colleagues observe.

Only 8% of men diagnosed with lung cancer were never-smokers, compared to 23% of women. The authors note that never-smokers are more likely to receive aggressive or complete treatment and respond well to treatment.

Similarly, tumor-related factors together explained about one-quarter of the overall sex disparity in survival.

Screening Guidelines

Commenting on the findings in an accompanying editorial, Claudia Poleri, MD, Hospital María Ferrer, Buenos Aires, Argentina, says that this Australian study provides “valuable information.”

“The risk of dying from lung cancer was significantly higher for men than for women,” she writes. “Differences in treatment-related factors explained 50% of the sex survival differential, followed by lifestyle and tumor-related factors (28% and 26%, respectively).

“Nevertheless, these differences alone do not explain the higher survival in women,” she comments.

“Does it matter to analyze the differences by sex in lung cancer?” Poleri asks in the editorial, and then answers herself: “It matters.”

“It is necessary to implement screening programs and build artificial intelligence diagnostic algorithms considering the role of sex and gender equity to ensure that innovative technologies do not induce disparities in clinical care,” she writes.

“It is crucial to conduct education and health public programs that consider these differences, optimizing the use of available resources, [and] it is essential to improve the accuracy of research design and clinical trials,” she adds.

Yu and Poleri declared no relevant financial interests.

Journal of Thoracic Oncology. Published online February 3, 2022. Full text. Editorial.

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