Exploration of the lymphadenectomy strategy for elderly pancreatic ductal adenocarcinoma patients undergoing curative-intent resection

Abstract

There has been a long-standing controversy regarding the number of lymph nodes (LNs) examined intraoperatively for accurate lymphatic staging and significantly better survival of patients with pancreatic ductal adenocarcinoma (PDAC), and no consensus has been reached for the elderly with the age of over 75 years. Given these, the present study aims to investigate the appropriate number of examined lymph nodes (ELNs) for elderly patients mentioned above. In this study, population-based data on 20,125 patients in 2000 to 2019 from the Surveillance, Epidemiology, and End Results database were reviewed retrospectively. The eighth edition staging system of the American Joint Committee on Cancer (AJCC) was applied. Propensity score matching (PSM) was performed to reduce the effects of multiple biases. By using binomial probability law and maximally selected rank statistics, the minimum number of ELN (MNELN) for accurate nodal involvement assessment and optimal ELN number for significantly better survival were calculated, respectively. In addition, Kaplan-Meier curves and Cox proportional hazard regression models were constructed for further survival analysis. As a result, 6623 patients were enrolled in total in the study. Elderly patients had fewer lymph node metastases and a smaller lymph node ratio (LNR) (all P<0.05). However, poorer overall survival (OS) and cancer-specific survival (CSS) of elderly patients were observed in each pN stage (all P<0.05), except for CSS in N2. The proportions of N2 and N0 stages increased and decreased respectively with increasing number of ELN significantly. MNELN for accurate nodal assessment was 19 according to binomial probability law, and the optimal ELN number for significantly better survival was 17. Additionally, the number of ELN (<17 or ≥17) was also considered a strong prognostic predictor for elderly PDAC patients (≥75 years) in the Cox proportional hazard regression model (Overall survival: hazard ratio [HR]=0.74, 95% confidence interval [CI]: 0.65-0.83, P<0.001; Cancer-specific survival: HR=0.75, 95% CI: 0.66-0.85, P<0.001). In conclusion, extended lymphadenectomy is suitable for elderly PDAC patients undergoing curative-intent surgery owing to an accurate assessment of nodal status and improved long-term prognosis. However, a random, prospective clinical trial is warranted before the recommendation of extended lymphadenectomy for the elderly.

Keywords: Pancreatic ductal adenocarcinoma; accurate staging; elderly patients; examined lymph node; extended lymphadenectomy; long-term survival.

Figure 1

Flow chart for the patient selection process.

Figure 2

Epidemiological trends for PDAC patients in various age groups. A. Trends for the number of patients. B. Trends for the number of patients with nodal metastasis.

Figure 3

The status of nodal involvement for PDAC patients in different age groups. A. Number of positive nodes in various age groups. B. Lymph node ratio in various age groups.

Figure 4

The status of nodal involvement for PDAC patients. A. Number of positive nodes in patients with ages of <75 and ≥75 years. B. Lymph node ratio of patients in the two age groups. C. Proportions of pN0, pN1, pN2 for patients in different ELN groups.

Figure 5

The distribution of propensity scores. A. Distribution of propensity scores. B. The proportion of propensity scores before and after matching.

Figure 6

OS and CSS for patients in various groups. A, B. OS and CSS for patients with different pN, respectively. C, D. OS and CSS for pN0 patients of the two age groups. E, F. OS and CSS for pN1 patients of the two age groups. G, H. OS and CSS for pN2 patients of the two age groups.

Figure 7

Analysis for optimal ELN number for significantly better survival. A, C. The appropriate ELN number for better OS and CSS. B, D. OS and CSS for patients with ELNs<17 and ≥17.