A study reveals that obesity and sex significantly influence liver recurrence and survival rates in pancreatic cancer patients post-surgery.

As the incidence of obesity continues to rise nationally and globally, a new observational study published in Cancer reports that liver recurrence and survival outcomes in patients with pancreatic adenocarcinoma (PDAC) after upfront surgical resection appeared to differ by biologic sex and obesity.¹

In a cohort of patients with PDAC who underwent a surgery-first (upfront) approach, females with obesity were observed to have the most favorable outcomes, exhibiting superior overall survival (OS) (median OS, 37 months; 95% CI, 30–46 months) and the lowest cumulative incidence of liver recurrence at 12 (13%; 95% CI, 7.2%–20%) and 24 months (15%; 95% CI, 8.7%–23%; P =.027) post-surgery compared with those of their female counterparts without obesity and males with and without obesity.

Further, a univariate model revealed a significant association between male sex and OS (HR, 1.24; 95% CI, 1.06–1.44; P =.007); a multivariate model found that only males with obesity had significant worse OS (HR, 1.56; 95% CI, 1.12–2.18; P =.009) compared with females with obesity.

“We infer therefore that there is something protective within the obese female liver or metabolism that may limit engraftment of metastatic disease, inhibit metastatic cell growth within the liver, or augment the antitumor effects of systemic chemotherapy,” hypothesized the authors, Judge et al, on the findings.¹ The authors also pointed to possible hormonal mechanisms driving disease recurrence.

As a retrospective study, there is an inherent potential for selection bias, as well as a lack of available information in medical records. For instance, the study did not account for prediagnosis BMI as this information was not available in the dataset, which may have altered the study cohort as weight loss is common with pancreatic cancer diagnoses. Acknowledging this limitation and the potential confounding influence of weight loss, the investigators excluded patients who received neoadjuvant chemotherapy, increasing the likelihood that patients would be in good physical condition.

Nevertheless, the differences uncovered by this study highlight a novel interaction between sex and obesity in shaping outcomes, lending to future inquiries into host biology, as well as the noteworthy impact of sex and obesity on recurrence in the liver, a common site of PDAC recurrence associated with the poorest survival outcomes.

“The impact of obesity and sex on liver recurrences may allow for personalized prognostication among patients with resected pancreatic cancer, and provides a framework for preclinical investigations into the mechanism of liver metastasis formation on the basis of clinically relevant variables, including biologic sex and obesity status,” added the investigators.

Couresy: Targetted Oncology