Lymph Node Metastatic Patterns and Survival Predictors Based on Tumor Size in Pancreatic Ductal Adenocarcinoma

Abstract

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Its larger mass size is widely acknowledged to be associated with increased lymph node (LN) metastatic potential. However, the quantitative relationships between tumor size and LN metastasis or survival remain unclear. Thus, this study aims to quantitatively identify the objective relationship between tumor size and prevalence of LN metastases across primary tumor size spectrums. METHODS: 9,958 resected PDAC patients without distant metastasis were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The prevalence of LN metastases, LN ratio (LNR) and N2/N1 ratio were assessed amongst different tumor sizes, and the relationships were depicted by matched curves.RESULTS: In the enrolled cohort, age, tumor site, grade, American Joint Committee on Cancer (AJCC) 8th node staging, tumor size, chemotherapy and radiotherapy were identi ed as signi cant independent predictors for overall survival (OS) and cancer-speci c survival (CSS). For tumors within 1-40 mm in size, the prevalence of node positive disease is closely modelled using a logarithmic formula [0.249×ln (size) + 0.452] × 100%, and then uctuated between 70.0% and 80.0% when beyond 40 mm. The mean LNR increased in a stepwise manner as tumor size increased from 1-5 mm (LNR=0.024) to 41-45 mm (LNR=0.177); then, beyond 45 mm, it plateaued near 0.170. N2/N1 ratio gradually increased along with tumor size from 1-5 mm (N2/N1=0.286) to 41-45 mm (N2/N1=1.016), and when tumor size reached to 41-45 mm or more, the ratio stabilized around 1.000. CONCLUSION: Regional LN involvement demonstrated a logarithmic growth with increasing tumor sizes in resectable PDAC patients. The probability of metastasis in each regional LN for resectable PDAC patients with tumors greater than 40 mm in size was near 17.0% and their overall prevalence of LN metastasis was 70%-80%. Among which, 50% of patients had an N2 stage.

KRAS mutant–driven SUMOylation controls extracellular vesicle transmission to trigger lymphangiogenesis in pancreatic cancer

“…Lymphangiogenesis is well characterized as an essential step in LN metastasis in various cancers ( 37 ). Clinical evidence has shown that a high density of lymphatic vessels in PDAC is associated with increased LN metastasis and decreased OS ( 38 , 39 ). Currently, the universally acknowledged mechanism for lymphangiogenesis mainly focuses on the VEGF-C–mediated lymphatic pathways ( 3 , 40 ).…”

Extensive lymphadenopathy leading to cancerous pericardial effusion and tamponade in a T1 pancreatic head adenocarcinoma: a case report

“…The peripancreatic regional lymph nodes are frequently involved by disease (8). Larger tumor size (T stage) is widely acknowledged to be associated with increased lymph node metastasis (7,9). Resectable pancreatic cancers are typically in the earliest stages of the disease (stage 1A, 1B or 2A) and any nodal involvement outside the field of disease indicates unresectable disease (6).…”

Clinical value of extended lymphadenectomy in radical surgery for pancreatic head carcinoma at different T stages

“…Muralidhar et al [ 35 ] reported that lymph-node metastasis was more likely to occur in patients with larger pancreatic tumors at advanced T stages, illustrating the potential correlation between the T stage and lymph-node metastasis. Pu et al [ 10 ] found that the lymph-node metastasis rate reached a plateau of 70%-80% in patients with pancreatic tumors of > 40 mm diameter, and that about 50% of patients with stage-T3 pancreatic carcinoma and lymph-node metastasis were categorized as stage N2. After researching the mode of lymph node metastasis in pancreatic carcinoma patients, Kanda et al [ 11 ] reported that distant lymph-node metastasis was seen only in stage-T3- and -T4 pancreatic carcinoma, with station-16 metastasis observed in 10.7% and 33.3% of cases, respectively.…”

“…In our study, the positive lymph node count and long-term prognosis after ELD were not improved in patients with stage-T1 and -T2 disease. Radical resection can be achieved with SLD in these patients due to the relatively low lymph-node metastasis rate and absence of distant lymph-node metastasis[ 10 , 11 ], which may explain the limited benefit of ELD in these cases. The clinical value of ELD in patients with stage-T1 and -T2 PHC needs to be analyzed further.…”

“…Song et al [ 9 ] reported that patients with higher T-stage gastric cancer tend to have higher lymph-node metastasis rates, and confirmed the potential beneficial effect of extensive station-7 lymph-node resection. Considering the positive correlation between the lymph-node metastasis rate and tumor size in patients with PHC, as well as the tendency for distant lymph-node metastasis in advanced PHC[ 10 , 11 ], the selective performance of ELD in patients with PHC of higher T stages may improve the PHC prognosis. In this study, we evaluated the effect of ELD on the long-term prognoses of patients with PHC of different T stages, and the potential clinical value of this procedure.…”