| Small pancreatic ductal adenocarcinoma (≤ 2 cm): different imaging and clinicopathologic features according to extrapancreatic extension
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer, ranking among the top causes of cancer-related death worldwide, with a 5-year survival rate of approximately 12%. The prognosis remains poor, mainly due to late diagnosis, and only a small percentage of cases are deemed operable at the time of detection. While early detection and surgical resection can significantly improve outcomes, diagnosing small PDAs measuring 2 cm or less is particularly challenging, as they often do not present as distinct masses on imaging. The American Joint Committee on Cancer (AJCC) 8th Edition revised the tumor (T) staging criteria to be based solely on tumor size, excluding the concept of extrapancreatic extension (EPE), defined as the invasion of peripancreatic soft tissues (mesenteric fat, mesocolon, greater and lesser omentum, peritoneum), the extrapancreatic biliary system, the ampulla of Vater, or the duodenum. However, there has been debate over this decision, as some studies suggest that EPE remains an important prognostic factor that influences survival outcomes. This retrospective study examines the characteristics of small pancreatic ductal adenocarcinomas (s-PDA) in relation related to EPE and tries to identify significant imaging and clinicopathologic features that could predict cancer recurrence after surgical resection, to assess whether EPE in small tumors should still be considered clinically relevant. This study included 142 patients with surgically resected s-PDA, identified from a hospital database spanning from 2004 to 2021. Tumor size was ≤2 cm, fulfilling the AJCC 8th Edition T1 criteria. Preoperative imaging, with CT or MRI, was reviewed by two abdominal radiologists, who evaluated tumor size, diameter of the main pancreatic duct (MPD) and common bile duct (CBD), tumor-vessel relationships, the presence of extrapancreatic neural invasion (EPNI), metastatic lymph nodes (LNs), and resectability. Two expert pathologists retrospectively reviewed the gross and microscopic descriptions of the resected specimens, collecting data regarding the diagnosis, differentiation, location of tumor, size of tumor, depth of invasion, presence of venous invasion, presence of perineural invasion, tumor (T) and nodal (N) status according to AJCC 8th Edition staging system, and resection status according to the International Union Against Cancer. Patients were followed postoperatively to assess recurrence and recurrence-free survival (RFS). Of 142 patients with s-PDA, 78,2% (111/142) were found to have extrapancreatic extension, even though the tumor sizes were small. This challenges the notion that small tumor size alone implies early or localized disease. Imaging findings of s-PDA according to EPE Tumor size on CT was larger in cases with EPE (18,2 mm vs. 14,3 mm, p = 0,01). Abutment or encasement of the superior mesenteric vein (SMV) was more frequent in patients with EPE (40,9% vs. 13,8%, p = 0,02). Although EPE was present in most cases, only a small portion of tumors were visible as distinct hypoattenuating or hypointense masses on imaging, with many appearing isoattenuating or iso-intense, making detection difficult. In these cases, secondary signs such as duct dilatation were essential for diagnosis. Dilation of the main pancreatic duct or the common bile duct was common (CT: 75,4%; MRI: 82,6%), though not significantly different between groups. | Recurrence and Prognostic Indicators The recurrence rate was notably higher in patients with EPE (53,2%) compared to those without (32,3%), and the median recurrence-free survival was significantly shorter (24 months vs 102 months). Among the CT findings, only the vessel relationship of the SMV was significant in the univariate Cox regression analysis. Tumor size (both pathologic and on MRI) and EPNI were independent predictors of recurrence. Specifically, EPNI observed on MRI had a high hazard ratio (HR 3,341, p = 0,002), indicating a strong correlation with cancer recurrence. While imaging-detected EPNI was present in only a small fraction of cases (around 8-13%), pathological examination revealed a much higher rate (59,2%), highlighting the limitations of imaging in detecting EPNI and emphasizing the need for radiologists to look for secondary signs and known nerve invasion pathways. The study results raise important concerns about the current staging system for pancreatic cancer. Although the AJCC 8th Edition excludes EPE from T staging, this study, supported by a few other larger studies, suggests that EPE is highly prevalent even in small tumors and is strongly associated with worse outcomes. This implies that excluding EPE from staging criteria may overlook an essential prognostic factor. Furthermore, the study highlights the critical role of preoperative imaging, not just in detecting the tumor itself, but in evaluating features that correlate with aggressive disease, such as vessel involvement and EPNI. Despite the technical challenges, particularly in identifying isoattenuating tumors, imaging remains a key tool for assessing resectability and potential prognosis. This study concludes that extrapancreatic extension is common and clinically significant even in small (≤ 2 cm) pancreatic ductal adenocarcinomas. Tumors with EPE are generally larger and more aggressive, with a significantly higher chance of recurrence after surgery. Therefore, imaging findings, especially tumor size and SMV involvement, are essential for preoperative evaluation and prognosis. EPNI remains a challenging imaging finding, difficult to differentiate, even though several other studies, in addition to this one, have reported that EPNI represents a significant prognostic factor in pancreatic cancer. The authors suggest that reconsidering the role of EPE in staging systems could improve prognostic accuracy and patient management strategies. Dr. Irene Panozzo is a third-year Radiology resident at the University of Verona, Italy. She completed her undergraduate medical degree at the University of Padua. She has taken interest in both diagnostic and interventional radiology, with particular focus on abdominal imaging. |