Impact of neoadjuvant FOLFIRINOX over upfront resection in borderline resectable pancreatic cancer—an international, multicentre, real-world analysis

•Real-world outcomes in BR pancreatic cancer.•Neoadjuvant FOLFIRINOX associated with improved survival versus upfront surgery.•Pooled NATs not associated with improved outcomes.•No benefit from neoadjuvant gemcitabine and nab-paclitaxel versus upfront surgery. BackgroundThis study explores the potential benefits of neoadjuvant chemotherapy in borderline resectable (BR) pancreatic adenocarcinoma. Despite neoadjuvant treatment (NAT) increasingly being utilised, uncertainty remains as to the optimal approach.Patients and methodsThis study assessed clinical outcomes for 218 consecutive BR patients from the PURPLE registry. We compared initial surgery (IS) to NAT overall, and between different chemotherapy regimens.ResultsOf 1314 non-metastatic patients enrolled, 218 (17%) were considered BR. Of 28 planned for IS, 11/28 (39%) had their tumour excised compared to 68/152 (45%) with NAT (P = 0.59). Among those who received NAT and were resected, 52/100 (52%) received FOLFIRINOX (P = 0.234) and 8/28 (29%) received nab-paclitaxel with gemcitabine (nabPGem). There was no difference in median overall survival (OS) [hazard ratio (HR) 0.72, P = 0.199] between pooled NAT versus IS. Neoadjuvant FOLFIRINOX was associated with improved R0 resection rates (26% versus 7%, P = 0.07) and lower perineural invasion (51% versus 82%, P = 0.02) compared to IS in resected specimens. Neoadjuvant FOLFIRINOX improved OS (HR 0.53, P = 0.02), with a 23% improvement in 2-year OS. There was no difference in survival outcomes between IS and nabPGem.ConclusionsThe results of our study suggest that neoadjuvant FOLFIRINOX could improve R0 resection rate and OS compared to IS. This study explores the potential benefits of neoadjuvant chemotherapy in borderline resectable (BR) pancreatic adenocarcinoma. Despite neoadjuvant treatment (NAT) increasingly being utilised, uncertainty remains as to the optimal approach. This study assessed clinical outcomes for 218 consecutive BR patients from the PURPLE registry. We compared initial surgery (IS) to NAT overall, and between different chemotherapy regimens. Of 1314 non-metastatic patients enrolled, 218 (17%) were considered BR. Of 28 planned for IS, 11/28 (39%) had their tumour excised compared to 68/152 (45%) with NAT (P = 0.59). Among those who received NAT and were resected, 52/100 (52%) received FOLFIRINOX (P = 0.234) and 8/28 (29%) received nab-paclitaxel with gemcitabine (nabPGem). There was no difference in median overall survival (OS) [hazard ratio (HR) 0.72, P = 0.199] between pooled NAT versus IS. Neoadjuvant FOLFIRINOX was associated with improved R0 resection rates (26% versus 7%, P = 0.07) and lower perineural invasion (51% versus 82%, P = 0.02) compared to IS in resected specimens. Neoadjuvant FOLFIRINOX improved OS (HR 0.53, P = 0.02), with a 23% improvement in 2-year OS. There was no difference in survival outcomes between IS and nabPGem. The results of our study suggest that neoadjuvant FOLFIRINOX could improve R0 resection rate and OS compared to IS.