Feasibility, Safety, and Efficacy of Aggressive Multimodal Management of Elderly Patients with Pancreatic Ductal Adenocarcinoma
Authors: Qiao Guoliang , Fong Zhi Ven , Bolm Louisa , Fernandez del-Castillo Carlos , Ferrone Cristina R , Servin-Rojas Maximiliano , Pathak Priyadarshini , Lau-Min Kelsey , Allen Jill N , Blaszkowsky Lawrence S , Clark Jeffrey W , Parikh Aparna R , Ryan David P , Weekes Colin D , Roberts Hannah M , Wo Jennifer Y , Hong Theodore S , Lillemoe Keith D , Qadan Motaz 
Published: October 2023

Objective:
We aimed to evaluate the safety and efficacy of NAT followed by surgical resection in patients with PDAC aged ≥75 years.

Summary Background Data:
Whether administration of neoadjuvant therapy (NAT) followed by surgical resection in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is safe and effective is unknown.

Methods:
The present study is a three-part comparison of older (≥ 75 years) versus younger (< 75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with non-metastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older vs. younger patients who underwent NAT followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT followed by surgical resection vs. upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR), were compared. Propensity-score matching (PSM) analysis was performed to adjust for potential confounders.

Results:
In the first analysis, a lower proportion of older patients (n=40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared to younger patients (n=214) (65.0% vs. 81.4%, P=0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P=0.89) as well as surgical resection (57.5% vs 55.6%, P=0.70). In the second analysis, PSM was conducted to compare older (n=54) vs. younger patients (n=54) who underwent NAT followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in overall survival (OS) between older and younger patients (median OS: 16.43 months vs. 30.83 months, P=0.002), importantly, there was no significant difference in time to recurrence (TTR, median: 7.65 months vs. 11.83 months, P=0.215). In the third analysis, older patients who underwent NAT followed by surgical resection (n=48) were compared with similar older patients who underwent upfront surgical resection (n=48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs. 11.51 months, P=0.037) as well as TTR (median TTR: 8.81 months vs. 7.10 months, P=0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone.

Conclusions:
This comprehensive three-part study showed that administration of NAT followed by surgical resection appears to be safe and effective among patients ≥ 75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC.