Biological Sex Influences Cancer Outcomes and Treatment Side Effects, Australian Study Finds

An Australian-led study has identified significant differences in cancer outcomes and treatment-related side effects based on biological sex. The research indicates that women with advanced-stage cancers exhibit a lower risk of death and disease progression but a higher risk of experiencing severe side effects from cancer treatments compared to men.

Key Findings on Sex-Based Disparities

The study reported the following distinctions, observed across numerous advanced solid tumor types (11 to 12 types) and various treatment modalities including chemotherapy, targeted therapies, and immunotherapy:

• Female cancer patients had a 21% lower risk of death from cancer compared to male patients.
• Women also showed a 16% lower risk of disease progression.
• However, women experienced a 12% higher risk of severe side effects or toxicities from cancer treatments.

While the lower death risk for female participants was largely consistent, researchers noted that better overall survival rates for female patients were not statistically significant in five specific cancer types.

Methodology

The research, led by Adelaide University and published in the Journal of the National Cancer Institute, analyzed data from 39 clinical trials conducted between 2011 and 2021. The extensive dataset included 20,806 participants diagnosed with advanced-stage cancers, whose treatment evaluations were approved by the U.S. Food and Drug Administration (FDA). Tumor types examined included lung, colorectal, melanoma, and breast cancers.

Biological Sex as a Predictive Factor

Dr. Natansh Modi, lead author and lecturer at Adelaide University, highlighted the fundamental role of biological sex:

"Biological sex is a fundamental factor influencing immune function, drug metabolism, body composition, and tumor biology, positioning it as a predictor of outcomes in cancer care."

The consistency of these disparities across various tumor types and treatment modalities suggests that underlying biological mechanisms contribute to these differences, rather than solely drug-specific effects.

Implications for Cancer Care and Future Research

Dr. Modi noted that despite recommendations from regulatory and funding bodies, outcomes are not consistently reported by sex or factored into personalized treatment decisions. The findings imply a need for routinely reporting and acting on sex-specific evidence in clinical research, which could influence how drugs are evaluated and prescribed.

Associate Professor Magdalena Simonis, a GP and researcher with the University of Melbourne, recognized the observed differences and suggested that men might be disadvantaged due to a lack of sex-based research.

Simonis also indicated that while it might be premature to use biological sex as a prognostic factor in oncology at present, there is a need for increased funding and research into sex-differentiated studies and clinical trials.

The Adelaide University researchers emphasized that their analysis focused on baseline prognosis rather than sex-specific treatment effects. They concluded that the consistently poorer prognosis among men necessitates further investigation into biological, behavioral, sociological, and treatment-related drivers of this disparity.