Risk Factors for Early Disease-Related Mortality Among Patients with Localized Pancreatic Cancer Resected After Neoadjuvant Treatment.

[BACKGROUND] Following neoadjuvant treatment (NAT) and resection with radical intent, not all patients with pancreatic ductal adenocarcinoma (PDAC) seem to achieve a meaningful survival benefit, as some experience very-early recurrence and succumb shortly thereafter. This study aimed to identify preoperative risk factors of mortality within 1-year after NAT and surgery.

[PATIENTS AND METHODS] Retrospective analysis of all patients who underwent radical resection for PDAC after at least 3-months of NAT between January 2015 and March 2023. Early-death (ED) was defined as disease-related mortality within 12-months of surgery, excluding surgery-related mortality. Receiver operating characteristic (ROC) curve analysis was used to determine statistically derived thresholds for continuous variables. Multivariable logistic regression was conducted to identify factors associated with ED, which were subsequently evaluated in an external cohort.

[RESULTS] Overall, 418 patients were included. After a median follow-up of 37 months (95%CI 34-39), 44 patients (10.5%) experienced ED, with a median survival from diagnosis of 17 months (95%CI 15-18) and a disease-free survival of 4 months (95%CI 3-4). Radiological tumor size ≥ 25 mm (OR 3.81, 95%CI 1.84-7.91, p < 0.001) and CA19-9 ≥ 100 U/mL (OR 2.93, 95%CI 1.41-6.05, p = 0.004) were independently associated with ED. These associations were confirmed in the external cohort of 473 patients (OR 3.93, 95%CI 2.39-6.45, p < 0.001 and OR 1.81, 95%CI 1.08-3.03, p = 0.023, respectively).

[CONCLUSIONS] In this study, post-treatment CA19-9 ≥ 100 U/mL and tumor size ≥ 25 mm were associated with an increased risk of early-death after resection following NAT, representing warning signs in surgical decision-making and preoperative counselling.