Pattern Of reCurrence after pancreatEctoMy and ONcological treatment (POCEMON) for pancreatic ductal adenocarcinoma

Comprehensive Cancer Network (NCCN) guidelines, with the surgical goal of achieving complete macroscopic tumor removal through R0 or R1 resection. Neoadjuvant treatment consisted of modern chemotherapy regimens with or without radiotherapy. Postoperative surveillance included clinical assessment, cross-sectional imaging, and serial CA19-9 monitoring. Recurrence was classified according to anatomical site, timing, and modality of detection, including both radiological recurrence and biochemical recurrence defined by isolated CA19-9 elevation. The primary endpoint of the study was the characterization of recurrence patterns. Secondary endpoints included overall survival (OS), recurrence-free survival (RFS), post-recurrence survival (PRS), time to recurrence, and survival outcomes according to recurrence type and treatment strategy. Statistical analyses were performed using Kaplan-Meier methods and Cox proportional hazards regression models. The overall study cohort comprised approximately 2500 patients from international centers. A total of 1176 patients who underwent curative-intent resection for pancreatic ductal adenocarcinoma (PDAC) between 2015 and 2023 were included in the preliminary POCEMON cohort analysis. During follow-up, recurrence developed in more than half of the patients, with liver recurrence representing the most frequent pattern, followed by locoregional and pulmonary recurrence. Significant differences emerged among recurrence types in terms of timing, CA19-9 levels, treatment allocation, and survival outcomes. Pulmonary recurrence was associated with the longest recurrence-free interval, lower tumor marker levels at relapse, and the most favorable prognosis, particularly in patients eligible for local treatment strategies. In contrast, liver recurrence was characterized by earlier relapse, higher CA19-9 levels, and significantly poorer survival outcomes, reflecting a more aggressive biological behavior. Peritoneal and multi-site recurrences were similarly associated with diffuse disease and limited survival. Local treatment strategies, including surgery and stereotactic body radiotherapy, were more commonly adopted in selected patients with lung and locoregional recurrence and were associated with prolonged post-recurrence survival compared with systemic therapy alone. However, multivariable analysis suggested that treatment selection and underlying tumor biology played a major role in determining prognosis. Recurrence after curative-intent resection for PDAC is characterized by marked biological and prognostic heterogeneity according to recurrence pattern. Pulmonary recurrence appears to represent a distinct and more indolent disease phenotype associated with improved survival outcomes and greater applicability of aggressive local treatment strategies, whereas liver and disseminated recurrences remain associated with poor prognosis and predominantly systemic disease behavior. These findings support the concept that recurrent PDAC should not be managed as a single clinical entity and highlight the importance of integrating recurrence pattern, disease-free interval, CA19-9 levels, disease burden, and patient performance status (ECOG) into post-recurrence therapeutic decision-making. Although systemic chemotherapy remains the standard treatment for most patients, selected local therapies may provide meaningful survival benefit in highly selected cases within a multidisciplinary and biologically informed treatment strategy. Further prospective studies are needed to refine recurrence-pattern-specific management algorithms and improve patient selection for aggressive post-recurrence interventions.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and lethal malignancies worldwide, with extremely poor long-term survival despite continuous advances in surgical and oncological treatment. Even after curative-intent resection, recurrence develops in up to 80% of patients within the first two years following surgery, representing the main determinant of prognosis. Patterns of recurrence after PDAC resection are highly heterogeneous and appear to reflect different biological behaviors of the disease. Liver metastases, which occur in approximately 30–50% of patients, are the most common form of relapse and are generally associated with aggressive disease progression and poor survival outcomes. Lung metastases, observed in around 10–20% of cases, are increasingly recognized as a distinct subgroup characterized by a slower disease course and improved post-recurrence survival, especially in selected patients eligible for surgery or stereotactic body radiotherapy (SBRT). Locoregional recurrence, involving the retroperitoneum or pancreatic bed, occurs in approximately 20–30% of patients and is associated with technically challenging management and limited survival. Peritoneal and multi-site recurrence typically indicate diffuse systemic disease and carry the poorest prognosis. An additional clinical challenge is represented by biochemical recurrence, defined as a progressive increase in tumor markers in the absence of radiological evidence of disease. Although this pattern is increasingly recognized in clinical practice, its optimal management remains poorly standardized. The growing adoption of neoadjuvant therapy has also modified recurrence dynamics and may influence both recurrence timing and metastatic distribution, although its overall impact on recurrence biology remains incompletely understood. In this context, a better understanding of recurrence patterns and post-recurrence management strategies is essential to improve patient selection and optimize therapeutic decision-making. This retrospective multicenter study investigates recurrence patterns and management strategies following curative-intent resection for pancreatic ductal adenocarcinoma (PDAC), with particular focus on recurrence site, timing, biological behavior, and therapeutic approaches adopted in clinical practice. A comparative analysis between patients treated with neoadjuvant therapy and those undergoing upfront surgery was performed in order to evaluate potential differences in recurrence dynamics and survival outcomes. Particular attention was dedicated to post-recurrence management, including systemic therapy, surgery, stereotactic radiotherapy, and other local treatment strategies, as well as to challenging scenarios such as biochemical recurrence without radiological evidence of disease. The primary objectives of the study were to characterize recurrence patterns and evaluate treatment strategies and outcomes after recurrence. Secondary objectives included the comparison of recurrence patterns between treatment groups, the analysis of survival according to recurrence type, the evaluation of biochemical recurrence management, and the identification of factors associated with aggressive post-recurrence treatment. This retrospective multicenter observational cohort study was conducted according to the STROBE guidelines and included patients treated at high-volume pancreatic cancer centers. Patients who underwent curative-intent resection for histologically confirmed pancreatic ductal adenocarcinoma (PDAC) between January 2015 and December 2023 were considered eligible, proved they had no metastatic disease at the time of surgery, available baseline imaging and CA19-9 measurements, and at least 18 months follow-up. Patients were stratified according to treatment strategy into neoadjuvant therapy and upfront surgery groups. Tumor resectability was assessed by institutional multidisciplinary teams (MDTs) according to National