Overview: How Sex and Obesity Interact in Pancreatic Cancer Surgery
Obesity is an escalating global health issue, intertwined with cancer risk and outcomes. A new observational study published in Cancer examines how biologic sex and obesity together shape liver recurrence and overall survival (OS) in patients who underwent upfront surgical resection for pancreatic ductal adenocarcinoma (PDAC). The findings point to a striking interaction: obese women fared best, while men with obesity showed the poorest survival among the groups studied. This has implications for prognostication, patient counseling, and future research into the biology of liver metastasis in pancreatic cancer.
Study Design and Population
The research analyzed 939 patients treated at Memorial Sloan Kettering Cancer Center from 2012 to 2022 who had resected PDAC and underwent a surgery-first approach. Patients were categorized by sex (male or female) and by body mass index (BMI) into six levels: underweight, normal, overweight, and three obesity classes (I–III). The primary outcomes were liver recurrence at 12 and 24 months after surgery and overall survival from the date of surgery. The analysis used univariate and multivariable models, adjusting for adjuvant therapy, vascular and perineural invasion, tumor stage, surgical margins, and comorbidity burden.
Key Findings: Obesity and Sex Modulate Liver Recurrence and OS
In this surgery-first cohort, female patients with obesity demonstrated the most favorable prognosis. They had a median OS of 37 months and the lowest liver recurrence rates at 12 months (13%) and 24 months (15%). In contrast, other groups—females without obesity and males with or without obesity—had comparatively higher recurrence and shorter survival. A univariate analysis found that male sex was associated with worse OS (hazard ratio [HR] 1.24; P = .007). In multivariate models, the adverse association persisted primarily in male patients with obesity (HR 1.56; 95% CI 1.12–2.18; P = .009) when compared with obese females.
The authors hypothesized that protective factors in the obese female liver or related metabolism might limit metastatic engraftment, suppress metastatic cell growth, or enhance the efficacy of systemic chemotherapy. Hormonal mechanisms are also considered potential drivers of these sex- and weight-related differences in recurrence and survival.
Why This Matters: Potential for Personalized Prognostication
The findings suggest that a patient’s sex and obesity status could refine prognosis after surgical resection for PDAC. If confirmed in further studies, clinicians could incorporate sex- and obesity-based risk stratification into postoperative plans, follow-up intensity, and adjuvant treatment decisions. This work also opens avenues for laboratory studies to uncover biologic pathways that govern liver metastasis in the context of obesity and sex hormones, with the goal of developing targeted interventions.
Limitations and Considerations
As a retrospective study, the analysis is subject to inherent biases, including possible selection bias and incomplete data. Notably, the study did not have prediagnosis BMI data, which could influence interpretation since weight loss is common with pancreatic cancer. To reduce confounding from preoperative fitness, researchers excluded patients who received neoadjuvant chemotherapy. While this strengthens the focus on a surgery-first population, residual confounding remains a possibility, and external validation is warranted.
Future Directions
Researchers emphasize the need for prospective studies to verify sex- and obesity-related differences in liver recurrence and survival after PDAC surgery. Elucidating the biological mechanisms behind these associations—such as adipose-tissue–driven hormonal effects, liver microenvironment, and chemotherapy interactions—could inform precision medicine approaches for pancreatic cancer. In the meantime, clinicians should consider sex and BMI as part of holistic decision-making and patient counseling after upfront surgery.
Clinical Takeaways
– Among patients undergoing upfront surgery for PDAC, obese females showed the best OS and the lowest liver recurrence at 12 and 24 months.
– Male sex was linked to worse OS, with obesity amplifying the risk.
– The study highlights opportunities for personalized prognosis and motivates mechanistic research into sex- and obesity-related biology in pancreatic cancer.
