Women are more likely to survive cancer than men, but face a higher risk of serious and adverse side effects from treatment, according to a landmark international study. Published by Chhetri et al in the Journal of the National Cancer Institute, the research identified consistent differences between male and female patients with cancer in both survival and treatment toxicity.
Female patients had a 21% lower risk of death compared with male patients, yet a 12% higher risk of severe toxicities.
These sex-based differences were largely consistent across 12 advanced solid tumor types as well as treatment modalities including chemotherapy, targeted therapies, and immunotherapy, suggesting they stem from underlying biological mechanisms, not just drug-specific effects.
Importantly, rather than focusing on how specific cancer treatments affect men and women differently—the traditional approach—the study looked at whether sex itself predicts survival and toxicity, regardless of treatment type.
Lead author Natansh Modi, PhD, of Adelaide University, said the study provides some of the clearest evidence yet that sex is a key predictor of outcomes in cancer care.
“Sex is a fundamental biological factor that influences immune function, drug metabolism, body composition, and tumor biology,” he stated. “Yet despite longstanding recommendations from regulatory and funding bodies to report outcomes by sex, it is still treated as an afterthought in many trials and is rarely factored into baseline risk or used to personalize treatment decisions.”
“Our study addresses this by looking at whether sex itself predicts survival and toxicity across a wide range of cancers and therapies. The results were clear: women had a 21% lower risk of death compared to men, but they also faced a 12% higher risk of severe side effects. Women demonstrated a survival advantage, but at the cost of increased severe toxicity,” he concluded.
The study analyzed data from more than 20,000 patients across 39 clinical trials supporting U.S. Food and Drug Administration oncology drug approvals between 2011 and 2021, and spanned 12 advanced solid tumor types, including lung, colorectal, skin, and breast cancers.
The findings have important implications for how drugs are evaluated and prescribed, strengthening the case for routinely reporting and acting on sex-specific evidence in clinical research.
Researchers are now calling for sex to be recognized as a core prognostic factor in oncology—both in clinical trials and everyday cancer care.
“This is about improving outcomes for every cancer patient,” Dr. Modi said. “If women are living longer but experiencing more severe side effects, we need to acknowledge that and respond to it. At the same time, we need to better understand why male patients appear to have poorer survival.”
The team says further research is needed to understand the biological mechanisms driving these differences, including drug exposure, immune regulation, hormonal influences, and body composition.
DISCLOSURE: For full disclosures of the study authors, visit academic.oup.com/jnci.
