Australian study reveals why men have higher risk of dying from lung cancer

Lung cancer

By Michael Woodhead

12 May 2022

Men have a 43% greater risk of dying from lung cancer than women but most of the survival difference can be explained by known prognostic factors, Australian research shows.

Key drivers of sex-related survival disparities in lung cancer mortality included histologic subtype, cancer stage, treatment received and smoking status, according to findings published by researchers from The Daffodil Centre,  Sydney University and Cancer Council NSW.

They said it had long been known that women tended to survive a lung cancer diagnosis longer than men but the factors related to sex-related disparities had remained largely elusive until now.

They therefore investigated lung cancer outcomes and prognostic factors for 488 women and 642 men who were enrolled in the 45 and Up Study between 2006–2009.

During follow up to 2015 they found that overall survival for women was significantly longer than for men (median 1.28 versus 0.77 years; HR for men = 1.43, 95% CI: 1.25–1.64, p < 0.0001).

Their initial findings, published in the Journal of Thoracic Oncology, showed that survival disparity remained when each subgroup of major prognostic factors (histologic subtype, stage at diagnosis, treatment received, and smoking status) was evaluated separately.

On multivariable analysis, treatment-related factors explained half of the survival difference, followed by lifestyle and tumour characteristics (explaining 28%, 26%, respectively). After adjusting for all major known prognostic factors, the excess risk for men was reduced by more than 80%.

The researchers said their findings confirmed and extended those of previous Australian studies into sex disparities in lung cancer survival, providing more robust data based on people in community settings rather than just hospital-based patients undergoing treatment with curative intent.

“We found that approximately half of the observed sex survival disparity was explained by differences in receipt of anticancer treatments within six months after diagnosis. This could partly be due to a lower proportion of men having surgery within six months than women (17% versus 25%), which may be due to patient-related factors that also correlate with poorer survival,” they said.

The finding that the sex disparity remained even among those who did not receive any treatment for their cancer within six months suggested that lung cancer in women may have a different natural history, they added.

Immunologic differences might explain the survival disparity among untreated patients, the researchers said, noting that the densities of anti-tumour memory B cells had been shown to be higher in the lung adenocarcinoma tissues of female patients compared to male patients.

Recent studies had also revealed differences in the expression and mutation rates of several related genes between sexes, including the EGFR, K-ras, and p53.

“These biological differences may be a factor in women’s better response to chemotherapy and radiotherapy for both SCLC  and NSCLC, which in turn may explain some of the sex survival disparity observed in this study,” they said.

Tumour-related factors were also important contributors to the sex disparity in survival, which together explained approximately 26% of the overall sex disparity.

The proportion of cases with adenocarcinoma was higher for women than men in the study (51% versus 33%) and thus the higher survival for those with adenocarcinoma may explain some of the survival disparity between the sexes, the authors suggested.

“An understanding of the drivers of the sex differences in lung cancer survival is critical to the improvement of outcomes for both men and women with lung cancer. Given that treatment differences are an important factor even when adjusting for age and comorbidities, qualitative studies to evaluate the interactive roles of patients’ and family members’ choices and perceptions of treatment could yield some insights on additional drivers for these survival differences,” they concluded.

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