Effect of neoadjuvant radiotherapy on survival of non-metastatic pancreatic ductal adenocarcinoma: a SEER database analysis

Abstract

Background: Neoadjuvant radiotherapy has been shown to improve marginal negative resection and local control of Pancreatic Ductal Adenocarcinoma (PDAC). However, whether it improves overall survival (OS) in patients with non-metastatic PDAC remains controversial. Therefore, the purpose of this study was to analyze the benefits of only surgery, neoadjuvant radiotherapy, adjuvant radiotherapy, and surgery plus chemotherapy for OS in patients with non-metastatic PDAC.

Methods: PDAC diagnosed by surgical histopathology in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016 was selected. Kaplan-Meier analysis was used to compare the prognosis of patients with different treatments. Cox proportional risk model was used to analyze independent predictors of OS. Propensity score matching (PSM) was used to analyze the tumor prognosis of different treatment methods.

Results: Before PSM analysis, the OS of surgery plus chemotherapy (HRs = 0.896, 95%CIs, 0.827-0.970; P = 0.007) were significantly better than the other three treatments for stage T1-3N0M0 PDAC patients. For stage T1-3N + M0 patients, adjuvant radiotherapy (HRs = 0.613, 95% CIs, 0.579-0.649; P < 0.001) had significantly better OS than surgery plus chemotherapy and neoadjuvant radiotherapy. For stage T4N0M0 patients, neoadjuvant radiotherapy (HRs = 0.482, 95% CIs, 0.347-0.670; P < 0.001) had significantly better OS than surgery plus chemotherapy and adjuvant radiotherapy. For stage T4N + M0 patients, neoadjuvant radiotherapy (HRs = 0.338, 95% CIs, 0.215-0.532; P < 0.001) had significantly longer OS than adjuvant radiotherapy and surgery plus chemotherapy. Even after PSM, Chemotherapy plus surgery was still the best treatment for T1-3N0M0 patients. Postoperative adjuvant radiotherapy had the best prognosis among T1-3N + M0 patients, and neoadjuvant radiotherapy was the best treatment for T4 patients.

Conclusions: For patients with non-metastatic PDAC, neoadjuvant radiotherapy, adjuvant radiotherapy and surgery plus chemotherapy were superior to only surgery in OS. For patients with stage T4 non-metastatic PDAC, neoadjuvant radiotherapy had the potential to be strongly recommended over adjuvant radiotherapy and surgery plus chemotherapy. However, neoadjuvant radiotherapy failed to benefit the survival of T1-3N0M0 stage patients, and surgery plus chemotherapy was preferred. For T1-3N + M0, neoadjuvant radiotherapy had no obvious advantage over adjuvant radiotherapy or surgery plus chemotherapy in OS, and adjuvant radiotherapy was more recommended.

Keywords: Neoadjuvant radiotherapy; Overall survival; Pancreatic ductal adenocarcinoma; Propensity score matching; SEER.

Fig. 1

Procedures for inclusion and exclusion of PDAC patients

Fig. 2

OS estimated with the Kaplan-Meier method for non- metastatic PDAC. A.OS estimated with the Kaplan-Meier method for PDAC patients with T1-3N0M0 stage receiving different treatment methods (surgery alone versus (vs.) adjuvant radiotherapy: p = 0.223; surgery alone vs. neoadjuvant radiotherapy: p = 0.027; surgery alone vs. surgery plus chemotherapy: p = 0.007;adjuvant radiotherapy vs. surgery plus chemotherapy: p = 0.023). B. OS estimated with the Kaplan-Meier method for PDAC patients with T1-3N + M0 stage receiving different treatment methods (surgery alone versus (vs.) adjuvant radiotherapy: p < 0.001; surgery alone vs. neoadjuvant radiotherapy: p = 0.001; surgery alone vs. surgery plus chemotherapy: p < 0.001;adjuvant radiotherapy vs. neoadjuvant radiotherapy: p = 0.017;adjuvant radiotherapy vs. surgery plus chemotherapy: p < 0.001). C. OS estimated with the Kaplan-Meier method for PDAC patients with T4N0M0 stage receiving different treatment methods (surgery alone versus (vs.) adjuvant radiotherapy: p = 0.353; surgery alone vs. neoadjuvant radiotherapy: p < 0.001; surgery alone vs. surgery plus chemotherapy: p = 0.001;adjuvant radiotherapy vs. neoadjuvant radiotherapy: p < 0.001;adjuvant radiotherapy vs. surgery plus chemotherapy: p < 0.001;neoadjuvant radiotherapy vs. surgery plus chemotherapy: p < 0.001). D. OS estimated with the Kaplan-Meier method for PDAC patients with T4N + M0 stage receiving different treatment methods (surgery alone versus (vs.) adjuvant radiotherapy: p = 0.353; surgery alone vs. neoadjuvant radiotherapy: p < 0.001; surgery alone vs. surgery plus chemotherapy: p < 0.001;adjuvant radiotherapy vs. neoadjuvant radiotherapy: p < 0.001;adjuvant radiotherapy vs. surgery plus chemotherapy: p < 0.001;neoadjuvant radiotherapy vs. surgery plus chemotherapy: p < 0.001)

Fig. 3

The Kaplan-Meier curve of overall survival of PDAC patients after PSM. A.Comparison of OS between the neoadjuvant radiotherapy group and the only surgery group for T1-3N0M0 stage (P = 0.176); B. Comparison of OS between the neoadjuvant radiotherapy group and the adjuvant radiotherapy group for T1-3N0M0 stage (P = 0.125); C. Comparison of OS between the neoadjuvant radiotherapy group and the surgery plus chemotherapy group for T1-3N0M0 stage (P = 0.025); D. Comparison of OS between the neoadjuvant radiotherapy group and the only surgery group for T1-3N + M0 stage (P = 0.036); E. Comparison of OS between the neoadjuvant radiotherapy group and the adjuvant radiotherapy group for T1-3N + M0 stage (P = 0.022); F. Comparison of OS between the neoadjuvant radiotherapy group and the surgery plus chemotherapy group for T1-3N + M0 stage (P = 0.541); G. Comparison of OS between the neoadjuvant radiotherapy group and the only surgery group for T4 stage (P < 0.001); H. Comparison of OS between the neoadjuvant radiotherapy group and the adjuvant radiotherapy group for T4 stage (P = 0.002); I. Comparison of OS between the neoadjuvant radiotherapy group and the surgery plus chemotherapy group for T4 stage (P = 0.028).