Elderly patients with pancreatic ductal adenocarcinoma: clinical features, perioperative outcomes, genomic landscape, and survival

The proportion of elderly patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC) is increasing as the global population ages. However, the clinical and molecular characteristics of elderly patients with PDAC remain incompletely understood. We retrospectively analyzed 3414 patients who underwent pancreatic resection for PDAC between January 2012 and December 2024. Elderly patients (≥ 70 years, n = 956, 28.0%) were compared with non-elderly patients (< 70 years, n = 2458). Clinical characteristics, perioperative outcomes, genomic profiles, laboratory parameters, inflammatory indices, and survival outcomes were assessed. Somatic alterations were analyzed in a subset of 452 patients with available sequencing data. Elderly patients presented less frequently with abdominal pain (44.5% vs. 49.9%, p = 0.004) and had higher rates of peripancreatic fat infiltration (88.4% vs. 83.7%, p < 0.001). They had significantly lower albumin, prealbumin, hemoglobin, and lymphocyte counts, and higher C-reactive protein, resulting in worse Glasgow Prognostic Score, Systemic Inflammation Score, and Prognostic Nutritional Index (all p < 0.05). Adjuvant chemotherapy (51.0% vs. 63.8%, p < 0.001), adjuvant radiotherapy (6.8% vs. 9.6%, p = 0.010), and neoadjuvant chemotherapy (8.8% vs. 15.1%, p < 0.001) were used less frequently in elderly patients. Despite lower treatment intensity, elderly patients had lower rates of clinically significant postoperative pancreatic fistula (5.1% vs. 7.3%, p = 0.023) but longer hospital stays (≥ 10 days: 48.8% vs. 43.9%, p = 0.010) and a trend toward higher severe complications (Clavien-Dindo III-V: 9.8% vs. 7.7%, p = 0.054). Somatic mutation frequencies in key driver genes were comparable between groups, with no difference reaching statistical significance after multiple testing correction. Survival outcomes were significantly worse in elderly patients, with median overall survival of 21.1 months (95% CI 19.8–22.4) compared to 25.1 months (95% CI 23.7–26.5) in non-elderly patients ( p < 0.001), and median disease-free survival of 13.5 months (95% CI 12.6–14.5) compared to 14.3 months (95% CI 13.5–15.1) in non-elderly patients ( p = 0.007). Elderly patients with PDAC represent a distinct clinical population characterized by poorer nutritional and inflammatory status, lower treatment intensity, and significantly worse survival compared to non-elderly patients. These findings support age-appropriate surgical and oncologic management while recognizing the limited role of routine genetic testing in elderly patients without strong family histories. The survival disadvantage in elderly patients highlights the need for optimized perioperative care and treatment strategies tailored to this vulnerable population.