The Organ-Specific Prognostic Value of TP53 Mutations in Pancreatic Cancer Patients with Oligometastasis Following Surgical Resection

Brady A Campbell; Angela Xiong; Sagar D Patel; Thomas McPhaul; Shuang Zhang; Christopher R Shubert; Kelly Lafaro; Richard A Burkhart; William R Burns; Stephen Yang; Lei Zheng; Jin He

doi:10.1097/SLA.0000000000006823

The Organ-Specific Prognostic Value of TP53 Mutations in Pancreatic Cancer Patients with Oligometastasis Following Surgical Resection

Ann Surg. 2025 Jul 1. doi: 10.1097/SLA.0000000000006823. Online ahead of print.

Authors

Brady A Campbell^{1

2}, Angela Xiong², Sagar D Patel^{1

2}, Thomas McPhaul³, Shuang Zhang¹, Christopher R Shubert¹, Kelly Lafaro¹, Richard A Burkhart¹, William R Burns¹, Stephen Yang⁴, Lei Zheng^{2

3}, Jin He^{1

3}

Affiliations

¹ Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
² The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Pancreatic Cancer Precision Medicine Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Thoracic Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.

PMID: 40590443
DOI: 10.1097/SLA.0000000000006823

Abstract

Objective: To investigate the prognostic value of KRAS and TP53 in oligometastatic pancreatic ductal adenocarcinoma (PDAC) and compare oncologic outcomes after curative-intent surgery.

Summary background data: The current patient selection criteria for surgery on PDAC oligometastasis remain unclear.

Methods: PDAC patients with oligometastasis who underwent surgical resection between 2009 and 2023 were identified. Inclusion criteria required metachronous pulmonary or synchronous liver metastasectomy. Multivariable cox-regression analysis was used to study the prognostic value of PDAC driver genes (KRAS, TP53, SMAD4, and CDKN2A) in overall survival.

Results: We identified 73 patients including 28 metachronous lung oligometastasis and 45 synchronous liver oligometastasis. Molecular profiling data were available for 20 (71%) lung oligometastasis and 28 (62%) liver oligometastasis patients. Liver oligometastasis patients had higher CA19-9 levels as well as perineural and lymphovascular invasion rates compared to the lung oligometastasis cohort (all P<0.03). Lung oligometastasis patients demonstrated lower College of American Pathologist (CAP) scores of the primary tumor than the liver oligometastasis cohort (P=0.002). Median overall survival (mOS) was longer in the lung oligometastasis cohort than in the liver oligometastasis cohort (59 vs. 11 months, P<0.001). In the liver cohort, TP53 mutations (HR 10.82, P=0.007) and node-positive disease (HR 14.52, P=0.004) were associated with shorter mOS. No significant prognostic factors were identified in the lung cohort.

Conclusion: Patients with liver oligometastasis had significantly worse mOS and higher CAP scores than lung oligometastasis. TP53 mutations were associated with worse outcomes. Preoperative molecular profiling might help select patients with PDAC oligometastasis for surgery.

Keywords: NGS; Oligometastatic; PDAC; Pancreatic Neoplasms; genetic sequencing; pancreatic surgery.