When to Operate After Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer: A Critical Review and Multidimensional Decision Framework.

Abstract

Background: Surgical timing after neoadjuvant therapy for borderline resectable pancreatic cancer remains difficult because post-treatment imaging may not reliably distinguish residual tumor from fibrosis, whereas tumor biology and patient fitness strongly influence surgical benefit.

Methods: We performed a critical narrative review of studies and guidelines addressing surgical timing, radiological response, tumor-marker dynamics, pathological response, and physiological readiness after neoadjuvant therapy for borderline resectable pancreatic cancer.

Results: Current evidence supports a multidimensional approach rather than reliance on anatomical imaging alone. Informative tumor-marker trajectories, especially carbohydrate antigen 19-9 when reliable and alternative markers such as Duke pancreatic monoclonal antigen type 2 when carbohydrate antigen 19-9 is non-informative, are central to assessing systemic disease control. Selective use of liver magnetic resonance imaging, diffusion-weighted magnetic resonance imaging, and positron emission tomography-based modalities may help clarify discordant scenarios or detect occult metastatic disease. Patient fitness, including performance status, nutritional reserve, organ function, and recovery from treatment-related toxicity, remains essential before exploration.

Conclusion: Surgical timing after neoadjuvant therapy for borderline resectable pancreatic cancer should integrate biology, anatomy, and patient condition. A biology-first multidisciplinary framework may help avoid futile pancreatectomy while preserving timely surgical opportunities for appropriate candidates.