Effect of duration of neoadjuvant therapy on pancreatic cancer outcomes: a systematic review and meta-analysis

The aim of theis study was toevaluate impact of duration of neoadjuvant treatment (NAT) on surgical resection rate, resection margin, response to treatment, and survival in patients with pancreatic ductal adenocarcinoma (PDAC).

All randomised controlled trials (RCTs) of NAT in patients with PDAC were included. Effect sizes were determined for surgical resection rate, R0 resection, radiological response to NAT and 1- to 5-years survival.

Twenty-three RCTs (1880 patients) were included. NAT duration≤8 weeks was associated with significantly higher surgical resection rate [66.7 % (95 % CI 57.4 %-76.1 %)] compared with NAT duration >8 weeks [33.5 % (95 % CI 22.1 %-45.0 %)]. The difference remained significant when only resectable [73.9 % (95 % CI 64.3 %-83.5 %) vs 44.7 % (95 % CI 15.9 %-60.6.%)], borderline resectable [66.4 % (95 % CI 46.6 %-86.1 %) vs 22.5 % (95 % CI 18.2 %-26.8 %)], or mixed borderline resectable/locally advanced PDAC [60.6 % (95 % CI 48.2 %-73.0 %) vs 35.0 % (95 % CI 27.6 %-42.4 %)] were considered. Moreover, when only NAT with chemotherapy considered, resection rate remained significant in favour of NAT duration≤8. No significant difference was found in R0 resection rate, partial response, stable disease, or disease progression between two groups. Intention-to-treat respected 1-, 3-, 5-years survival were comparable.

NAT duration >8 weeks may be associated with a reduced surgical resection rate and no apparent improvement in negative resection margin in patients with PDAC, particularly borderline resectable cases. However, it may have comparable survival to NAT duration ≤8 weeks. Future randomised evidence is needed to overcome the limitations associated with current evidence.