Association of Adjuvant Chemotherapy in Patients With Resected Pancreatic Adenocarcinoma After Multiagent Neoadjuvant Chemotherapy

Abstract

Importance: The total number of patients with pancreatic ductal adenocarcinoma (PDAC) who receive neoadjuvant chemotherapy (NAC) is increasing. However, the added role of adjuvant chemotherapy (AC) in these patients remains unknown.

Objective: To evaluate the association of AC with overall survival (OS) in patients with PDAC who received multiagent NAC followed by curative-intent surgery.

Design, setting, and participants: This retrospective, matched-cohort study used data from the National Cancer Database and included patients with PDAC diagnosed between 2010 and 2018. The study included patients at least 18 years of age who received multiagent NAC followed by surgical resection and had available records of the pathological findings. Patients were excluded if they had clinical or pathological stage IV disease or died within 90 days of their operation.

Exposures: All included patients received NAC and underwent resection for primary PDAC. Some patients received adjuvant chemotherapy.

Main outcomes and measures: The main outcome was the OS of patients who received AC (AC group) vs those who did not (non-AC group). Interactions between pathological findings and AC were investigated in separate multivariable Cox regression models.

Results: In total, 1132 patients (mean [SD] age, 63.5 [9.4] years; 577 [50.1%] male; 970 [85.7%] White) were included, 640 patients in the non-AC group and 492 patients in the AC group. After being matched by propensity score according to demographic and pathological characteristics, 444 patients remained in each group. The multivariable Cox regression model adjusted for all covariates revealed an association between AC and improved survival (hazard ratio, 0.71; 95% CI, 0.59-0.85; P < .001). Subgroup interaction analysis revealed that AC was significantly associated with better OS (26.6 vs 21.2 months; P = .002), but the benefit varied by age, pathological T category, and tumor differentiation. Of note, AC was associated with better survival in patients with any pathological N category and positive margin status.

Conclusions and relevance: In this cohort study, AC following multiagent NAC and resection in patients with PDAC was associated with significant survival benefit compared with that in patients who did not receive AC. These findings suggest that patients with aggressive tumors may benefit from AC to achieve prolonged survival, even after multiagent NAC and curative-intent resection.

Figure 1.. Flowchart of Study Cohort

AC indicates adjuvant chemotherapy; CA 19-9, carbohydrate antigen 19-9; NAC, neoadjuvant chemotherapy; PDAC, pancreatic ductal adenocarcinoma.

Figure 2.. Overall Survival Stratified by Adjuvant Chemotherapy (AC) in Matched Patients

Survival time was measured from 3 months after surgery. HR indicates hazard ratio.

Figure 3.. Forest Plot of the Association of Adjuvant Chemotherapy (AC) With Mortality in Subgroup Analyses

Median survival time was measured from 3 months after surgery. The position of each square represents the point estimate of the association of AC. All interactions were tested in 1 model adjusted for age, sex, facility type, Charlson-Deyo comorbidity index, year of diagnosis, tumor location, carbohydrate antigen 19-9 level, pathological TN stage, margin status, tumor differentiation, neoadjuvant radiotherapy, adjuvant radiotherapy, and AC. Adjusted hazard ratios (aHRs) are estimated for each interaction coefficient using the non-AC group as the reference. NA indicates not applicable.