What determines the resectability of pancreatic adenocarcinoma in an adult patient?

Resectability of Pancreatic Cancer

Pancreatic cancer resectability is determined primarily by the degree of tumor contact with major peripancreatic vessels (superior mesenteric artery, celiac axis, common hepatic artery, portal vein, and superior mesenteric vein), with tumors classified as resectable, borderline resectable, locally advanced, or metastatic based on standardized NCCN criteria that assess vessel involvement. 1

Primary Determinants of Resectability

Anatomical Criteria Based on Vessel Involvement

Resectable disease requires all of the following 1, 2:

• Clear fat planes around the celiac axis, hepatic artery, and SMA 1
• No radiographic evidence of SMV or portal vein abutment, distortion, tumor thrombus, or venous encasement 1
• Arterial vessel-tumor contact <180° without deformation 2
• No venous involvement or only minimal contact 2

Borderline resectable disease is defined by 1:

• Tumor abutment on portal vein or SMV with or without venous deformity 1
• Limited encasement of mesenteric and portal vein (short segment occlusion with suitable vessel for anastomosis above and below) 1
• Encasement of a short segment of hepatic artery without extension to celiac axis 1
• Tumor abutment of SMA involving ≤180° of the artery circumference 1

Locally advanced (unresectable) disease involves 1:

• Tumor involvement of celiac axis or SMA >180° or with deformation 1
• Unreconstructible venous occlusion 1

Absence of Metastatic Disease

No evidence of distant metastases is mandatory for both resectable and borderline resectable classifications 1. This includes:

• No visceral, peritoneal, or pleural metastases 1, 3
• No metastases to lymph nodes beyond the field of resection 1, 3
• No liver metastases 3

Secondary Biological and Conditional Factors

While anatomical criteria form the foundation, the 2023 ESMO guidelines emphasize that biological and conditional features should also be assessed using IAP consensus criteria 1. These include:

Patient-Related Factors

• Performance status (ECOG PS) - PS ≥2 indicates poor surgical candidacy 1
• Nutritional status - albumin <35 g/L associated with worse outcomes 1
• Comorbidities that affect surgical risk 1

Tumor Biology Markers

• CA 19-9 levels - values >500 IU/mL suggest aggressive biology and should prompt consideration of neoadjuvant therapy rather than upfront surgery 4, 5
• Tumor size ≥3 cm independently predicts lower resectability and higher risk of margin-positive resection 5, 6, 7

Likelihood of R0 Resection

The probability of achieving negative surgical margins (R0 resection, defined as no cancer cells within 1 mm of all resection margins) is a key criterion 1. This is why:

• Borderline resectable lesions have higher likelihood of R1 (positive margin) resection and should NOT undergo upfront surgery 1, 2
• R0 resection is the strongest prognostic indicator for long-term survival 1

Imaging Modalities for Assessment

CT or MRI with pancreatic protocol serves as the primary imaging modality 2, 4, with:

• >90% positive predictive value for determining unresectability 1, 4
• <50% positive predictive value for confirming resectability 1, 2 - this is a critical limitation

EUS provides complementary information on vessel invasion and allows tissue diagnosis 1, 4

Staging laparoscopy should be considered to exclude clinically occult metastases, particularly in borderline cases, preventing unnecessary laparotomy in 20-40% of cases 2, 4

Critical Pitfalls to Avoid

Do not rely solely on CT/MRI to confirm resectability - the positive predictive value is insufficient (<50%), meaning many "resectable" tumors on imaging prove unresectable at surgery 1, 2

Do not perform upfront surgery on borderline resectable tumors - the high R1 resection rates (33% in one study) worsen outcomes compared to neoadjuvant therapy first 1, 2, 6

Do not attempt arterial resections during pancreatoduodenectomy - these are associated with increased morbidity and mortality without survival benefit 1, 2

Venous resection (PV or SMV) is acceptable if needed for R0 resection, but is associated with lower R0 rates and poorer survival due to inherent tumor aggressiveness 1

Multidisciplinary Team Decision-Making

All resectability determinations must involve multidisciplinary tumor board discussion in expert centers 1. This is essential because:

• Only 15-20% of patients have truly resectable disease at diagnosis 1, 4
• Approximately 40% of patients deemed resectable on imaging are found unresectable at surgical exploration 5
• The feasibility to receive and complete adjuvant treatment affects prognosis and should factor into surgical decision-making 1