Feasibility, Safety, and Efficacy of Aggressive Multimodal Management of Elderly Patients With Pancreatic Ductal Adenocarcinoma

Ann Surg. 2024 Jul 1;280(1):118-125. doi: 10.1097/SLA.0000000000006131. Epub 2023 Oct 13.

Abstract

Objective: To evaluate the safety and efficacy of neoadjuvant therapy (NAT), followed by surgical resection in patients with pancreatic ductal adenocarcinoma (PDAC) aged ≥75 years.

Background: Whether administration of NAT, followed by surgical resection in elderly patients with 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 nonmetastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older versus 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 versus 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 with 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) versus 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 OS between older and younger patients (median OS: 16.43 vs 30.83 months, P = 0.002), importantly, there was no significant difference in TTR (median: 7.65 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 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, seems 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Pancreatic Ductal* / mortality
  • Carcinoma, Pancreatic Ductal* / surgery
  • Carcinoma, Pancreatic Ductal* / therapy
  • Feasibility Studies*
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • Humans
  • Irinotecan / administration & dosage
  • Irinotecan / therapeutic use
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / therapeutic use
  • Pancreatectomy
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Pancreatic Neoplasms* / surgery
  • Pancreatic Neoplasms* / therapy
  • Propensity Score
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • folfirinox
  • Oxaliplatin