Background In recent years, the rising incidence of early-onset pancreatic cancer (EOPC) in patients younger than 50 years has attracted increasing attention. However, there are few studies on the clinicopathological features and treatment strategies of EOPC.

Objective To investigate the clinicopathological characteristics, treatment strategies, and prognostic factors in patients with EOPC.

Methods The clinical and treatment data of patients with EOPC from the First Medical Center of Chinese PLA General Hospital between January 2017 and December 2020 were retrospectively collected. The relationships between clinical features, treatment strategies and survival outcomes were analyzed.

Results A total of 272 patients with EOPC were included in this study. The median age of the overall cohort was 46 years (range, 23-50 years). Among them, male patients, patients with pancreatic head disease, and poorly differentiated adenocarcinoma accounted for 70.6%, 55.9%, and 50.3%, respectively. There were 22.8%, 28.3%, 18.0%, and 30.9% of patients in stage I, II, III, IV, respectively. There were 57%, 86.8%, 27.9%, 38.6%, and 31.6% of patients who underwent primary tumor surgery, chemotherapy, radiotherapy (RT), immunotherapy, and targeted therapy, respectively. The median overall survival (mOS) was 26.5 months (95% CI: 24.2-30.8); the 1-year, 2-year, and 5-year OS were 78.0%, 57.1%, and 24.3%, respectively. In patients with limited disease, the mOS of surgery alone group and adjuvant therapy group was 30.7 and 36.4 months, respectively (P=0.885). In patients with locally advanced disease, the mOS of RT-based comprehensive treatment (RT-based CMT) group, resection group, and chemotherapy alone group was 29.9, 16.9, and 15.7 months, respectively (P=0.207). All patients with metastatic disease received chemotherapy; the mOS of chemotherapy alone, RT, and resection groups was 8.3, 18.8, and 22.5 months, respectively (P=0.109). In patients with postoperative recurrence, the mOS of chemotherapy alone group and RT-based CMT group was 15.9 and 15.4 months (P=0.415), and the median progression-free survival (PFS) was 10.5 and 6.3 months (P=0.204), respectively. Multivariate analysis demonstrated that pathological differentiation (high and moderately vs. poorly; HR=0.66, 95% CI: 0.41-0.95), baseline CA19-9 level (>1 000 U·mL^-1 vs ≤1 000 U·mL^-1; HR=1.80, 95% CI: 1.16-2.81), clinical stage (IV vs I; HR=2.36, 95% CI: 1.12-4.99), surgery (yes vs no; HR=0.39, 95% CI: 0.22-0.69), and the number of chemotherapy cycles (>6 vs ≤6; HR=0.44, 95% CI: 0.29-0.67) were independent prognostic factors.

Conclusion Patients with EOPC exhibit a male predilection, earlier stage, and poor differentiation. There was no significant survival differences between surgery alone and adjuvant chemotherapy in patients with localized disease. RT-based CMT showed a trend towards improved survival in patients with locally advanced and metastatic disease, and RT is associated with better PFS in patients with postoperative recurrence.