Systemic neoadjuvant chemotherapy in modern pancreatic cancer treatment: a systematic review and meta-analysis

Abstract

Background: Pancreatic ductal adenocarcinoma remains a disease with a poor prognosis despite advances in surgery and systemic therapies. Neoadjuvant therapy strategies are a promising alternative to adjuvant chemotherapy. However, their role remains controversial. This meta-analysis aims to clarify the benefits of neoadjuvant therapy in resectable pancreatic ductal adenocarcinoma.

Methods: Eligible studies were identified from MEDLINE, Embase, Web of Science and the Cochrane Library. Studies comparing neoadjuvant therapy with a surgery first approach (with or without adjuvant therapy) in resectable pancreatic ductal adenocarcinoma were included. The primary outcome assessed was overall survival. A random-effects meta-analysis was performed, together with pooling of unadjusted Kaplan-Meier curve data.

Results: A total of 533 studies were identified that analysed the effect of neoadjuvant therapy in pancreatic ductal adenocarcinoma. Twenty-seven studies were included in the final data synthesis. Meta-analysis suggested beneficial effects of neoadjuvant therapy with prolonged survival compared with a surgery-first approach, (hazard ratio 0.72, 95% confidence interval 0.69-0.76). In addition, R0 resection rates were significantly higher in patients receiving neoadjuvant therapy (relative risk 0.51, 95% confidence interval 0.47-0.55). Individual patient data analysis suggested that overall survival was better for patients receiving neoadjuvant therapy (P = 0.008).

Conclusions: Current evidence suggests that neoadjuvant chemotherapy has a beneficial effect on overall survival in resectable pancreatic ductal adenocarcinoma in comparison with upfront surgery and adjuvant therapy. Further trials are needed to address the need for practice change.

Keywords: Cancer; Neoadjuvant; Pancreas; Surgery.

Figure 1

PRISMA flowchart of search strategy and results.

Figure 2

Forest plot of survival rates following neoadjuvant chemotherapy compared with surgery first (top) and adjuvant compared with no adjuvant therapy (bottom).

Figure 3

Forest plot of negative (R0) resection margins for patients receiving neoadjuvant chemotherapy compared with surgery first (CI, confidence interval; RR, relative risk).

Figure 4

Forest plot of morbidity rates for neoadjuvant chemotherapy compared with surgery first.

Figure 5

Funnel plot of hazard ratios for overall survival comparing neoadjuvant chemotherapy with surgery first (HR, hazard ration; SE, standard error).

Figure 6

Kaplan–Meier survival curve for overall survival for neoadjuvant chemotherapy and surgery first for patients with pancreatic ductal adenocarcinoma with number at risk values (P = 0.008).