C. Rieser1, S. Narayanan1, A. Paniccia1, N. Bahary2, D. Bartlett1, K. Smith3, A. Zureikat1 1University Of Pittsburg,Department Of Surgery,Pittsburgh, PA, USA 2University Of Pittsburg,Department Of Hematology & Oncology,Pittsburgh, PA, USA 3University Of Pittsburg,Department Of Medicine,Pittsburgh, PA, USA
Introduction: Neoadjuvant therapy is an emerging treatment strategy in patients with locally advanced and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, its role in resectable PDAC is unclear. Neoadjuvant therapy may offer early treatment for micrometastatic disease and increase multimodal therapy completion rates in the resectable cohort. However, this approach also entails increased risk of functional decline and treatment drop out. As elderly patients with PDAC represent a vulnerable population often underrepresented in clinical trials who are particularly vulnerable to these risks, we use decision analysis to examine optimal management in this group.
Methods: A Markov cohort decision analysis model (Figure 1) evaluated initial treatment options for a 60-year-old patient with resectable PDAC, estimating survival time over a lifetime horizon. Options were: 1) attempted pancreaticoduodenectomy with plan for subsequent adjuvant chemotherapy (Surgery first: SF); or 2) attempted neoadjuvant chemotherapy/chemoradiotherapy followed by restaging and, as appropriate, attempted pancreaticoduodenectomy with plans for subsequent adjuvant chemotherapy (NAT). Probabilities and survival durations were derived from clinical trial and retrospective data. One-way and probabilistic sensitivity analyses were performed to test model robustness. Subsequent analysis took the perspective of a 75-year-old patient with PDAC.
Results: In 60-year-olds with resectable PDAC, there was an incremental gain in survival with NAT approach of 6.1 mos (27.3 mos for NAT vs 21.2 mos SF). In 1-way sensitivity analyses, findings were sensitive to probability of no disease progression or functional decline on NAT (threshold at < 46.0%, base case 89.0%), probability of resectable disease on exploration on NAT pathway (threshold at < 47.0%, base case 88.0%), perioperative mortality risk post NAT (threshold at > 28.1%, base case 2.0%), and recurrence free survival duration with adjuvant therapy post NAT (threshold at < 4.9 mos, base case 18.9 mos). Results were insensitive to variation of other parameter values. On probabilistic sensitivity analysis, NAT was the dominant strategy in a robust majority of trials (99.6%) with a median survival benefit of 5.9 mos. In altering the base case for the 75-year-old scenario, NAT remained the dominant strategy with a survival benefit of 5.1 mos.
Conclusion: This analysis demonstrates patients with resectable PDAC benefit from a neoadjuvant approach. This benefit persists even in the elderly who face additional risks. The recurrence free survival benefit for elderly patients with neoadjuvant therapy compared to a surgery first approach requires further study to determine the precise survival benefit.
