This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Sarcopenia as a Marker of Immunometabolic Vulnerability in Pancreatic Ductal Adenocarcinoma
by
, and
Mukund Karthik
1,2,*,
Sara Shahrestani
1,3,
Jin-soo Park
1,4,
Christian Ratnayake
1,2 and
Charbel Sandroussi
1,2,4,5,* 1
Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia
2
Research, Innovation & Surgical Education (RISE), Sydney, NSW 2050, Australia
3
Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY 10029, USA
4
Department of Upper GI Surgery, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
5
Department of Upper GI Surgery, Chris O’Brien Lifehouse, Sydney, NSW 2050, Australia
*
Authors to whom correspondence should be addressed.
Cancers 2026, 18(8), 1205; https://doi.org/10.3390/cancers18081205
Submission received: 20 February 2026
/
Revised: 3 April 2026
/
Accepted: 8 April 2026
/
Published: 9 April 2026
(This article belongs to the Special Issue Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers)
Simple Summary
Pancreatic cancer has a very poor prognosis, even when surgery is possible. Many patients with pancreatic cancer have sarcopenia, that is, low muscle mass, which is linked to poorer survival and reduced ability to complete chemotherapy. Traditional approaches to address sarcopenia have focused on nutrition and exercise to build muscle, but these strategies have shown limited benefits in improving meaningful clinical outcomes. Growing evidence suggests that loss of muscle in pancreatic cancer reflects deeper problems in immune and metabolic function rather than physical weakness alone. Muscle and fat tissue actively influence immune responses, inflammation, and recovery after surgery. This review explores how sarcopenia may identify patients with reduced biological resilience who struggle to recover and tolerate cancer treatment after surgery. We propose that future prehabilitation strategies should focus on improving immune and metabolic health, alongside nutrition and exercise, to better support recovery and long-term outcomes after pancreatic cancer surgery.
Abstract
Despite advances in surgical technique and perioperative care, pancreatic ductal adenocarcinoma (PDAC) remains associated with poor survival. Sarcopenia is highly prevalent in PDAC and is consistently associated with inferior survival and reduced tolerance of systemic therapy. However, interventions primarily aimed at increasing muscle mass through nutritional supplementation and resistance-based exercise have yielded limited improvements in clinically meaningful postoperative outcomes. This has prompted increasing interest in sarcopenia as a marker of broader biological vulnerability rather than isolated physical deconditioning. Emerging clinical, translational, and experimental evidence demonstrates that skeletal muscle and adipose tissue function as active immunometabolic organs, and that cancer-associated inflammatory pathways drive early muscle loss, immune dysfunction, and impaired physiological recovery. Across multiple clinical cohorts, sarcopenia is reproducibly associated with worse overall survival and failure to complete adjuvant therapy, but not consistently with increased postoperative complications, suggesting that its prognostic relevance lies in impaired recovery and oncological fitness rather than immediate surgical risk. Translational studies further indicate that sarcopenia identifies patients with reduced antitumor immune competence, particularly in early-stage disease. This review synthesizes current evidence linking sarcopenia, immune dysfunction, and surgical outcomes in PDAC and examines implications for perioperative care. We propose that immunometabolic-informed prehabilitation, integrated with existing nutritional and exercise strategies, may represent a more effective approach to improving recovery, treatment tolerance, and durable oncological outcomes following PDAC resection.
