Sex and Gender Influence Outcomes in Colorectal Cancer

BARCELONA, SPAIN — Not all patients with colorectal cancer are the same, and more research is needed to examine differences between patients according to their sex, gender, and even menopause status, according to experts speaking here at the European Society for Medical Oncology (ESMO) Annual Meeting 2024.

“The concepts of gender and sex are not at all new in oncology, but what is needed is a renewed focus on them and the prospective collection of data in this regard,” said Kathrin Heinrich, MD, from the LMU University Hospital in Munich, Germany, speaking to Univadis Italy, a Medscape Network Platform.

Sex and Gender: What’s New? 

Speaking at the conference, Heinrich cited a 2020 study published in The Lancet that stated, “Sex and gender are the foundation of precision medicine, and their differences should guide decision-making processes to promote gender equity.”

Sex differences have clear biological and pathophysiological consequences in oncology. Available data show differences between men and women in terms of gene expression, epigenetics, metabolomics, tumor microenvironment, immune system, and microbiome. These are all critical for understanding tumor biology and identifying new treatments.

Colorectal cancer provides an excellent example of how sex differences can influence treatment outcomes.

From an incidence perspective, the numbers reported by the large epidemiological GLOBOCAN study are quite similar between the two sexes, with men accounting for 56% of patients and women for 44%.

However, there are noticeable differences in tumor characteristics, with women more frequently presenting with right-sided colon tumors and BRAF mutations; both features associated with a worse prognosis.

Sex also affects body composition, influencing the percentage of metabolically active body mass, which can alter the effectiveness and distribution of a drug and the necessary dose to achieve the desired effect.

“Despite this evidence, clinical practice often overlooks differences between the sexes when planning therapies,” Heinrich said, also recalling how in many cases the side effects of treatments — from chemotherapy to immunotherapy — differ in intensity and type between men and women.

Towards a More Targeted and Inclusive Approach

Sex is a well-defined concept from a biological standpoint and, consequently, the differences between the sexes are easy to identify. Analyzing gender differences is much more complex.

“It is not enough to tick the male or female box on a questionnaire. It is necessary to consider more complex aspects to measure, such as identity, role, and gender relations,” Heinrich said, also presenting a list of specific questionnaires to assess these components.

In today’s oncology, however, such questionnaires are mainly used to analyze secondary outcomes such as quality of life, while examples from other areas of medicine, particularly cardiology, show how questionnaires on gender can predict some clinical outcomes better than those on sex alone and that studies considering sex and gender are feasible.

Gender identity influences many aspects of health, such as attitudes towards prevention, the seeking of information and medical care, and risk behaviors. “The new approach to discussing sex and gender in oncology is to consider these factors in therapeutic decisions,” Heinrich told Univadis Italy. “I hope that within a few years this will be fully achievable, thanks to the inclusion in our studies of gender scores, ad hoc patient-reported outcomes, and information related, for example, to menopausal status or the number of pregnancies,” she added.

To harness the differences between sex and gender in favor of the patient, however, it is also necessary to change the approach to clinical studies. Currently, data on these aspects are typically collected retrospectively. However, they should be integrated prospectively from the study’s beginning.

“We look at increasingly smaller subgroups of patients, at mutations affecting 1%-2% of our patients, but we do not collect data on sex or menopausal status, which are actually extremely simple to record,” Heinrich said, calling for more inclusive studies, especially involving the LGBTQI+ community, traditionally excluded from clinical trials and many services.

“Fortunately, we live in an era in which sensitivity towards this community is continuously increasing. We must gather information on this population, which fully belongs to what we scientifically define as the ‘real-world’ approach.”

Heinrich declared honoraria, consulting and advisory roles, and travel support from several companies, including Amgen, BMS, Merck, MSD, Roche Janssen, Taiho, Servier, and streamed up.

Cristina Ferrario is a molecular biologist and former researcher in molecular oncology at three institutes in Milan. She has a master’s degree in communication and health from the University of Milan and a master’s degree in cancer genetics from the University of Pavia. She has worked as a science journalist for more than 20 years.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.