Early onset pancreatic Cancer: epidemiology, molecular features, and clinical outcomes

Background Early onset pancreatic cancer (EOPC), defined for the primary analysis as pancreatic ductal adenocarcinoma (PDAC) diagnosed before the age of 50 years, is an increasingly recognised clinical and epidemiological entity. Because published studies use heterogeneous age thresholds, the present review prespecified <50 years as the main definition and interpreted studies using other cutoffs in sensitivity or narrative analyses. Methods We systematically searched PubMed, EMBASE, and the Cochrane Library for studies published between January 1990 and December 2024 that reported outcomes specific to EOPC. Search terms were reformatted with standard quotation marks and included "pancreatic cancer", "pancreatic adenocarcinoma", "pancreatic ductal adenocarcinoma", "early onset", "young onset", "young adult", "age < 50", "age less than 50", and "premature". Meta-analytic procedures and epidemiological interpretation were re-reviewed with statistical/epidemiological input. Results 40 studies encompassing more than 285,000 patients were included. Global incident EOPC cases increased from 24,480 (1990) to 42,254 (2021), representing a 72·6% rise. Age-standardised prevalence rate increased by 17·0% (1·65 per 100,000 in 2021). EOPC patients have a 3·08% per year increase in the youngest age group (20-29 years) over 2010-2021. Germline pathogenic variants were identified in 17·3% of EOPC patients (vs 6·4% in older cohorts; OR 2·41, 95% CI 1·87-3·11). EOPC patients were more likely to receive treatment (OR 2·95, 95% CI 2·54-3·43; I² = 13%) and showed modestly improved overall survival (pooled HR 0·89, 95% CI 0·80-0·99; I² = 16%) compared with average or late onset disease. Conclusions EOPC is an increasingly recognised and clinically challenging subset of PDAC. The substantial hereditary and potentially actionable molecular burden supports universal germline testing and comprehensive tumour genomic profiling, particularly in younger patients and in KRAS wild-type disease. PARP inhibitors should be described as improving progression-free survival or disease-control outcomes in selected BRCA-mutated metastatic PDAC rather than as having established a statistically significant overall survival benefit.