Overview: A Novel Look at Sex, Obesity, and Pancreatic Cancer Outcomes
A recent observational study published in Cancer highlights how biologic sex and obesity may shape liver recurrence and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo upfront surgical resection. Analyzing a large cohort treated at Memorial Sloan Kettering Cancer Center from 2012 to 2022, researchers found that female patients with obesity demonstrated the most favorable outcomes, including longer median OS and lower liver recurrence at key checkpoints after surgery.
Key Findings: Who Fares Best and Why
Among 939 patients who had surgery-first management for resected PDAC, females with obesity showed the strongest survival advantage. Their median OS reached 37 months (95% CI, 30–46), and they exhibited the lowest rates of liver recurrence at 12 and 24 months post-surgery (13% and 15%, respectively; 95% CIs 7.2–20% and 8.7–23%). In contrast, other groups—females without obesity, and males with or without obesity—experienced comparatively higher recurrence and shorter survival, underscoring a potential interaction between sex and obesity in determining post-surgical trajectories.
In univariate analyses, male sex was associated with worse OS (hazard ratio [HR] 1.24; 95% CI, 1.06–1.44; P = .007). Multivariate analyses sharpened the finding: only males with obesity had significantly worse OS (HR 1.56; 95% CI, 1.12–2.18; P = .009) when compared with females with obesity, suggesting a protective element linked to female biology in the context of obesity.
Potential Mechanisms and Hypotheses
The authors speculate that a protective factor may exist within the obese female liver or metabolism, which could limit metastatic engraftment, slow metastatic cell growth, or enhance chemotherapy efficacy. Hormonal influences are also considered as possible drivers of the observed sex- and obesity-related differences in recurrence and survival. While the study does not establish causation, it raises compelling questions about host biology and tumor dynamics that warrant further investigation in preclinical models and prospective studies.
Study Design and Population
The objective was to assess how obesity and biologic sex relate to liver recurrence and OS in patients undergoing upfront surgical management for PDAC. This retrospective analysis drew on data from a single high-volume center, MSKCC, including patients treated between 2012 and 2022. All participants had a final pathologic diagnosis of PDAC and underwent upfront surgery, with a median age of 70 years and predominantly pancreaticoduodenectomy (approximately 73%).
Researchers categorized patients by sex and stratified BMI according to CDC/WHO standards into underweight, normal, overweight, and obesity classes I–III (BMI ranges provided in the study). They employed univariate models to explore associations with OS and built multivariable models adjusting for known prognostic factors, such as vascular and perineural invasion, pathologic T/N stage, surgical margins, and comorbidity burden. To ensure comparability, adjuvant therapy use was used to stratify baseline hazards.
Limitations and Considerations
As with all retrospective analyses, the study is subject to potential selection bias and unmeasured confounders. Notably, prediagnosis BMI data were unavailable, and weight loss common in pancreatic cancer could affect BMI categorization. The authors mitigated some confounding by excluding patients who received neoadjuvant chemotherapy, aiming to study individuals in comparatively good physical condition. Despite these caveats, the findings illuminate an intriguing interaction between sex and obesity in shaping liver recurrence and survival after surgery for PDAC.
Clinical and Research Implications
The study’s implications are twofold. Clinically, it introduces the possibility of personalized prognostication based on a patient’s sex and obesity status, potentially guiding post-surgical surveillance and adjuvant therapy choices. From a research perspective, the results justify exploring the underlying biology of liver metastasis in the context of sex hormones, adiposity, and metabolic state. Preclinical models and prospective trials could investigate how obesity-related factors influence hepatic metastasis and chemotherapy response in PDAC.
Conclusion: A Step Toward Personalized Prognosis in PDAC
Judge and colleagues’ work adds a meaningful dimension to PDAC management by highlighting how biologic sex and obesity interact to shape outcomes after upfront surgery. The observation that obese females may experience the most favorable prognosis prompts further investigation into sex-specific biology, metabolic influences, and the liver’s role in PDAC metastasis. As research advances, these insights could translate into tailored follow-up strategies and therapeutic approaches that improve survival for all patients facing pancreatic cancer.
References
Judge SJ, Manin E, Chou J, et al. Influence of biologic sex and obesity on liver recurrence and survival in patients undergoing upfront surgery for pancreatic adenocarcinoma. Cancer. 2025;131(18). doi:10.1002/cncr.70088
