Role of neoadjuvant chemo-radiotherapy for resectable and borderline resectable pancreatic adenocarcinoma- A systematic review and meta-analysis.

Background: Randomized trials and meta-analyses have indicated longer survival with neoadjuvant than with adjuvant therapy in patients with resectable or borderline resectable (R/BR) pancreatic adenocarcinoma. Despite the efficacy of chemotherapy, the role of radiotherapy as an adjuvant or neoadjuvant treatment for patients with R/BR pancreatic adenocarcinoma remains unclear. In this systematic review and meta-analysis, we compared the benefits of additional chemoradiotherapy (CRT) to neoadjuvant chemotherapy (NAC) with NAC alone for R/BR pancreatic adenocarcinoma.

Methods: A systematic literature search was conducted on Embase, Web of Science, PubMed, Cochrane, and Google Scholar. Median overall survival (OS) was the primary endpoint. Secondary endpoints included disease-free survival (DFS), resection rate and R0 resection rate.

Results: This review and meta-analysis included 31 prospective studies, of which 9 were randomized trials. In these studies, 658 patients from 14 study arms received NAC alone and 912 patients from 19 study arms received both NAC and CRT (NAC-CRT). The pooled median OS was 25.55 months (95% confidence interval [CI] = 21.59-30.24 months) for NAC alone and 17.55 months (95% CI = 16.47-18.70 months, p < 0.0001) for NAC-CRT. The pooled R0 resection rate was higher with NAC-CRT (83.43%) than with NAC (69.97%, p < 0.0001). No significant difference was observed in DFS or resection rate between the two groups. In patients who received 5 or more cycles of initial chemotherapy, NAC-CRT was associated with longer OS compared to NAC (23.30 vs 21.85 months, p = 0.856).

Conclusion: NAC provides significantly longer OS compared with NAC-CRT to R/BR pancreatic adenocarcinoma. NAC-CRT is associated with a significantly improved R0 resection rate. This positive local effect of CRT can be translated to extended survival when 5 cycles or more of NAC are prescribed.