Intraoperative Margin Analysis Does Not Improve Outcomes in Treatment-Naive or Neoadjuvantly-Treated Patients With Pancreatic Ductal Adenocarcinoma

Xing Li; Preeti Malik; Amarpreet Bhalla; John C McAuliffe; Nicole C Panarelli

doi:10.1016/j.modpat.2025.100826

Intraoperative Margin Analysis Does Not Improve Outcomes in Treatment-Naive or Neoadjuvantly-Treated Patients With Pancreatic Ductal Adenocarcinoma

Mod Pathol. 2025 Jun 20;38(11):100826. doi: 10.1016/j.modpat.2025.100826. Online ahead of print.

Authors

Xing Li¹, Preeti Malik¹, Amarpreet Bhalla¹, John C McAuliffe², Nicole C Panarelli³

Affiliations

¹ Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, New York.
² Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, New York; Department of Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, New York, New York.
³ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York. Electronic address: Nip9020@med.cornell.edu.

PMID: 40544923
DOI: 10.1016/j.modpat.2025.100826

Abstract

The prognostic relevance of intraoperative frozen section (IOF) margin analysis for patients with pancreatic ductal adenocarcinoma (PDAC) is debatable in both those treated with upfront surgery and neoadjuvant therapy. We analyzed the impact of intraoperative and final microscopic margin clearance in neoadjuvantly treated (n = 71) and treatment-naive (n = 109) patients with PDAC. Overall survival (OS) was longer in the treatment-naive (43 months) compared with the neoadjuvant (27 months) cohort (P = .02). Overall, 24 (34%) patients in the neoadjuvant and 22 (20%) patients in the treatment-naive groups had positive final margins, 13 and 10 of which were detected intraoperatively, respectively. At a median follow-up of 21 months, recurrence rates were 65% in the treatment-naive and 66% in the neoadjuvant cohorts and were similar regardless of margin status assessed via IOF or permanent sections. Disease-free survival (DFS) was significantly shorter in treatment-naive patients with positive (11 months) compared with negative (30 months) final margins (P = .03). Neither IOF nor final margin status was significantly associated with DFS in neoadjuvantly treated patients nor were they associated with OS in either cohort. Multivariate analysis showed that lymphovascular and perineural invasion were significantly associated with DFS, and lymphovascular invasion was significantly associated with OS. Our results suggest that IOF of the selected margins does not correlate with survival and is of limited utility in treatment-naive and neoadjuvantly treated PDAC patients.

Keywords: Whipple; distal pancreatectomy; frozen section; pancreaticoduodenectomy.