Abstract
Background/Objectives: Neoadjuvant therapy (NAT) improves surgical outcomes in pancreatic cancer, but its role in elderly patients remains unclear. Due to comorbidities and lower chemotherapy tolerance, assessing NAT's benefits and risks in this population is essential. This systematic review assesses the impact of NAT on overall survival (OS), surgical resection rates, and treatment-related toxicities(G3-4) in elderly patients with resectable, borderline, or locally advanced pancreatic cancer. Methods: A systematic search was conducted in PubMed, MEDLINE, EMBASE, Scopus, and Cochrane databases according to PRISMA guidelines. Studies reporting that NAT outcomes in elderly patients (≥70 years) were included. The Newcastle-Ottawa scale was used to assess study quality. Subgroup analyses compared NAT versus upfront surgery and outcomes in elderly versus younger patients. Results: Twelve studies (four prospective and eight retrospective) including 11,385 patients met the inclusion criteria. Among 9580 elderly patients, only 24% underwent NAT. NAT significantly improved R0 resection rates compared to upfront surgery (p < 0.001), and elderly patients receiving NAT had a median OS of 26.5 (range 15.7-39.1) months versus 20.3 months (range 11.5-23.8) of upfront surgery and versus 36.2 months (range 23.6-43.0) of NAT in young patients. Elderly patients experienced higher rates of major toxicities (17-57.5%). Personalized regimens, such as gemcitabine/nab-paclitaxel, were better tolerated than FOLFIRINOX. Conclusions: NAT is associated with improved survival and surgical outcomes in elderly pancreatic cancer patients, despite a higher risk of adverse events. Patient selection based on performance status rather than age alone is essential to optimize treatment benefits. Further prospective trials are needed to refine treatment approaches in this population.