Female Sex Is Associated With Improved Outcomes After Surgery for Pancreatic Neuroendocrine Neoplasms

Background Sex-related differences in oncologic outcomes are well established in pancreatic adenocarcinoma, but evidence in pancreatic neuroendocrine neoplasms (pNEN) remains limited. This study analyses the association of female sex and pre-menopausal status with perioperative outcomes and long-term survival after resection of non-functioning pNEN. Methods Patients who underwent pancreatic surgery for pNEN at Heidelberg University Hospital between 2001 and 2023 were analyzed. Outcomes included perioperative morbidity, disease-free survival (DFS) and overall survival (OS). Subgroups were stratified by age (<50, 50–65, >65 years) as a surrogate for menopausal status. Survival was estimated by Kaplan–Meier analysis and Cox regression was used to evaluate associations with OS. Results A total of 591 patients were included, of whom 257 (43.5%) were female. Age and ASA class were similar between sexes, while females had a lower BMI (24.6 vs 26.3 kg/m 2 , p<0.001). Resection types did not differ, but operative time was shorter in females (240 vs 265 min, p=0.003). Major complications were comparable (CDC ≥3a: 30.7% vs 34.1%, p=0.426), whereas severe complications (CDC ≥3b) occurred less often in females (9.7% vs 15.3%, p=0.048). TNM stage was similar, although males had more G3 tumors (15.9% vs 8.2%, p=0.019). Females had longer DFS (129.4 vs 75.5 months, p=0.006) and increased OS (5-year: 85.7% vs 70.5%; 10-year: 72.2% vs 61.1%; p=0.002). This effect was driven by patients <50 years, indicating a pre-menopausal survival advantage, as females had markedly better outcomes than age-matched males (p=0.022). On multivariable cox-regression analysis, female sex, age, grading and M-status remained independently associated with OS. Conclusions Female sex is associated with improved perioperative outcomes and increased long-term survival after resection in non-functioning pNEN. The survival benefit was largely determined by pre-menopausal patients, highlighting sex and menopausal status as relevant prognostic factors.