Women beat cancer better than men, but face severe reaction to treatment – study

Women with advanced cancer are living longer than men, but they are also paying a heavier price during treatment, according to a global study that is challenging how care is approached.

The research, published in the Journal of the National Cancer Institute and led by Australian researchers alongside an international team, is one of the largest efforts yet to understand how biological sex affects cancer outcomes, regardless of the drugs used.

By analysing data from more than 20,000 patients across 39 clinical trials that supported approvals by the United States Food and Drug Administration between 2011 and 2021, researchers found women had a 21 per cent lower risk of death compared to men.

But that advantage did not come easily.

Women were also 12 per cent more likely to experience severe side effects—classified as grade three or higher—which are serious enough to require hospital care or intensive treatment.

“The observation that females experienced a survival advantage despite higher toxicity has implications for trial design and for more individualised patient discussions regarding treatment risks and long-term care,” the researchers state in the report. 

The trend was consistent across 12 types of advanced solid tumours, including lung, colorectal and melanoma.

It also remained the same whether patients were treated with chemotherapy, targeted therapy or immunotherapy, suggesting the difference is rooted in biology rather than the type of treatment.

Researchers say one possible explanation is that women may be exposed to higher effective doses of cancer drugs.

Many treatments are given in fixed amounts, without adjusting for differences in body composition, kidney function or enzyme activity.

Because of this, women may end up with higher concentrations of the drugs in their bodies than men.

Unlike most clinical trials, which focus on how different groups respond to specific treatments, this study looked at whether sex itself can predict outcomes.

It found that being male or female may influence survival regardless of the therapy used.

The researchers caution that while the findings are clear at a population level, differences between tumour types and individual patients mean they should be applied carefully in clinical settings.

Still, poorer outcomes among men point to the need to better understand the biological, behavioural and social factors behind the gap.

“The consistently poorer prognosis among men underscores the need to investigate biological, behavioural, sociological and treatment-related drivers of this disparity,” the report states. 

The study’s design allowed scientists to isolate the effect of sex with a high level of accuracy.

Using individual patient data from industry-sponsored trials shared through data platforms, they were able to adjust for factors such as age, weight and overall health.

The findings raise important questions for cancer care.

If women are living longer but experiencing more severe side effects, there may be a need to rethink how treatments are dosed and how patients are supported during care.

At the same time, the lower survival rates seen in men suggest there is more to learn about how their cancers develop and progress.

Researchers say biological sex should be considered a key factor in cancer prognosis and in the design of future clinical trials.

They are calling for more studies into the underlying causes of these differences, including the role of hormones, the immune system and body composition, with the aim of improving care for both men and women.

They add that the finding that women live longer despite facing more toxicity could help guide more honest conversations with patients about the risks of treatment and what to expect over the long term.