Impact of neoadjuvant chemoradiotherapy on pathologic response in pancreatic ductal adenocarcinoma: A systematic review and meta-analysis

Background: The impact of chemoradiotherapy on pathologic response, resection margin, and survival benefit is still debated. The aim of this study was to compare the rate of pathologic complete response (pCR) in surgical resection following neoadjuvant chemotherapy vs. chemoradiotherapy, and secondarily, to compare the rate of R0 resection and Overall Survival (OS).

Methods: A systematic review on MEDLINE/PubMed, Embase, Cochrane, Web of Science and Google Scholar was conducted for studies published between 2012 and 2024 (PROSPERO CRD42022341467). All studies reporting clinical outcomes of patients with Pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant therapy were considered eligible for inclusion. A meta-analysis comparing the rate of pCR, R0 resection rate, and 3-year OS following Chemotherapy vs chemoradiotherapy in patients was performed. The overall quality of evidence was evaluated using a GRADE approach.

Results: Out of 5194 potentially relevant studies, 29 studies were considered eligible for full-text assessment, and 11 studies were included in the systematic review and in the meta-analysis. Of these, five were retrospective single-center, five retrospective multi-center studies, and one was a phase II multi-center RCT. Overall, 1830 Chemotherapy patients and 2299 Chemoradiotherapy patients were included in the meta-analysis. A statistically significant increased rate of pCR and R0 resections were found in chemoradiotherapy patients (OR 3.58, 95 % CI 2.47-5.18, p ≤ 0.00001) (OR 1.49, 95 % CI 1.17-1.90, p = 0.001), whereas 3-year OS (OR 1.07, 95 % CI 0.84-1.36, p = 0.6) did not differ significantly.

Conclusions: Chemoradiotherapy may have a positive impact on pathologic response and R0 resection rate, whereas a survival benefit was not reported.