Neoadjuvant treatment versus upfront surgery in borderline resectable and resectable pancreatic ductal adenocarcinoma: meta-analysis

Abstract

Background: Pancreatic cancer prognosis remains poor despite advances in adjuvant treatment. Neoadjuvant treatment may improve survival and disease-free survival. This meta-analysis evaluates the outcomes for patients with borderline-resectable (borderline-resectable pancreatic cancer) or resectable disease (resectable pancreatic cancer) in randomized trials of neoadjuvant therapy versus upfront surgery.

Methods: The review was performed according to PRISMA guidance. Articles were included from the start of the database until 1 May 2024. The primary outcome was overall survival. Secondary outcomes were progression-free survival, resection rate, R0 rate, N0 rate, vascular resection rate, surgical complications, significant adverse events and rates of adjuvant therapy. Data was collected from study manuscripts or through individual patient-level data extraction. Meta-analysis was performed using a random-effects model with subgroup comparisons for resectability status (resectable pancreatic cancer versus borderline-resectable pancreatic cancer) and treatment modality (chemotherapy versus chemoradiotherapy).

Results: Nine trials were included representing 1194 patients. Four trials recruited borderline-resectable pancreatic cancer, four resectable pancreatic cancer and one both. Four trials reported chemotherapy, four chemoradiotherapy and one both treatments. Neoadjuvant treatment improved overall survival (HR 0.73, 95% c.i. 0.55 to 0.98; P = 0.001) and progression-free survival (HR 0.80, 95% c.i. 0.65 to 0.99; P = 0.041). Subgroup analysis demonstrated neoadjuvant treatment improved overall survival for borderline-resectable pancreatic cancer (HR 0.60, 95% c.i. 0.38 to 0.96) but not resectable pancreatic cancer (HR 0.90, 95% c.i. 0.63 to 1.28). The overall resection rate was lower in neoadjuvant treatment (72.6% versus 80.6%, RR 0.94, 95% c.i. 0.89 to 0.99; P = 0.020). R0 rate (43.8% versus 23.0%, RR 1.35, 95% c.i. 1.16 to 1.57; P = 0.002) and N0 rate (30.9% versus 15.0%, RR 2.03, 95% c.i. 1.50 to 2.74; P = 0.001) was improved in neoadjuvant treatment. Significant adverse events occurred more frequently in neoadjuvant treatment (56.1% versus 27.0%, RR 1.92, 95% c.i. 1.28 to 1.89; P = 0.007).

Conclusion: Neoadjuvant treatment significantly improves survival in borderline-resectable pancreatic cancer but not resectable pancreatic cancer. It should be regarded as standard of care for these patients. Further work is needed to identify the optimum neoadjuvant regimen and a possible role in the treatment of resectable pancreatic cancer.

Fig. 1

Forest plot demonstrating pooled analysis of overall survival with subgroup analysis according to resectability criteria (BR-PDAC versus R-PDAC) as per NCCN criteria BR-PDAC, borderline resectable pancreatic cancer; R-PDAC, resectable pancreatic cancer; NCCN, National Comprehensive Cancer Network; PEXG, cisplatin, epirubicin, gemcitabine and capecitabine.

Fig. 2

Forest plot demonstrating pooled analysis of overall survival with subgroup analysis according to treatment regimen (chemotherapy versus chemoradiotherapy) PEXG, cisplatin, epirubicin, gemcitabine and capecitabine.

Fig. 3

Forest plot demonstrating pooled analysis of overall survival with subgroup analysis according to resectability criteria (BR-PDAC versus R-PDAC) as per NCCN criteria PEXG, cisplatin, epirubicin, gemcitabine and capecitabine; BR-PDAC, borderline resectable pancreatic cancer; R-PDAC, resectable pancreatic cancer; NCCN, National Comprehensive Cancer Network.

Fig. 4

Forest plot demonstrating pooled analysis of overall survival with subgroup analysis according to treatment regimen (chemotherapy versus chemoradiotherapy) PEXG, cisplatin, epirubicin, gemcitabine and capecitabine; mFOLFIRINOX, folinic acid, flurouracil, irinotecan and oxaliplatin.