What is the appropriate staging work‑up and treatment plan—including surgery, neoadjuvant or adjuvant chemotherapy, and systemic therapy for unresectable disease—for a patient with a confirmed pancreatic head adenocarcinoma?

Pancreatic Head Adenocarcinoma: Staging and Treatment Algorithm

Initial Staging Work-Up

Obtain multiphase contrast-enhanced multidetector CT (MDCT) of the chest, abdomen, and pelvis using a dedicated pancreatic protocol with late arterial and portal venous phases as the primary staging modality. 1, 2 This provides >90% positive predictive value for determining resectability. 2, 3

Essential Imaging Components:

• Triphasic MDCT with 3mm thin slices to assess tumor size, location, vascular involvement (celiac axis, superior mesenteric artery, portal vein), and distant metastases. 1, 2
• Chest CT with contrast to evaluate for lung metastases. 2
• MRI with gadolinium has superior sensitivity (90-100%) compared to CT (70-76%) for detecting liver metastases and can serve as a problem-solving tool. 1, 4

Additional Staging Tools:

• Baseline CA 19-9 measurement for prognostic information and treatment monitoring (if no cholestasis present). 1, 2
• EUS (endoscopic ultrasound) is NOT routinely recommended for staging but can guide biopsy when needed. 1
• Staging laparoscopy should be considered for patients with body/tail lesions, markedly elevated CA 19-9, or borderline resectable disease to detect occult peritoneal metastases before neoadjuvant therapy. 1, 5

Tissue Diagnosis Strategy

Proceed directly to surgery WITHOUT preoperative biopsy if imaging confirms resectable disease and the patient is a surgical candidate. 2, 3

When Biopsy IS Required:

• Unresectable or metastatic disease before systemic therapy. 2
• Neoadjuvant therapy is planned. 1, 2
• Ambiguous imaging findings. 2

Use EUS-guided fine needle aspiration (preferred over CT-guided) for highest accuracy and lowest tumor seeding risk. 1, 2 If initial biopsy is negative but clinical suspicion remains high, repeat EUS-FNA at a high-volume center. 1

Treatment Algorithm by Resectability Status

Resectable Disease (No Major Vascular Involvement)

Proceed directly to radical surgery with partial pancreaticoduodenectomy (Whipple procedure) aiming for R0 resection. 1, 5, 3

Surgical Considerations:

• R0 resection (negative microscopic margins) is the only independent prognostic factor and the primary surgical goal. 1, 6, 7
• Standard lymphadenectomy (hepatoduodenal ligament, common hepatic artery, portal vein, right celiac artery, right half of superior mesenteric artery) is recommended; extended lymphadenectomy provides no benefit. 1, 5, 2
• Document lymph node ratio (LNR) as LNR ≥0.2 indicates worse prognosis. 1, 5, 2
• Microscopic margin involvement occurs in >75% of cases even with meticulous technique and correlates with survival. 1, 5, 2

Adjuvant Therapy (MANDATORY):

All patients who undergo resection MUST receive 6 months of adjuvant chemotherapy with gemcitabine (1000 mg/m² over 30 minutes) or 5-FU. 1, 5, 2, 3 This improves 5-year survival from approximately 9% to 20%. 5, 3

• Adjuvant chemotherapy is beneficial even after R1 resection (positive margins). 1, 5
• Chemoradiation in the adjuvant setting should only be performed within clinical trials. 1

Borderline Resectable Disease (Limited Vascular Involvement)

Administer neoadjuvant chemotherapy (gemcitabine plus nab-paclitaxel) to achieve tumor downsizing and conversion to resectable status. 1, 5, 2, 3

• Consider staging laparoscopy before neoadjuvant therapy to rule out occult metastases. 1, 5
• Critical caveat: CT accuracy for determining resectability after neoadjuvant therapy is significantly reduced (58% vs 83% for upfront surgery) due to overestimation of vascular invasion and tumor size. 1, 8 Repeat high-quality MDCT or MRI after neoadjuvant therapy. 1
• Patients who develop metastases or progress locally during neoadjuvant therapy are NOT surgical candidates. 1

Locally Advanced Unresectable Disease (Celiac Axis or SMA Involvement = T4)

Initiate systemic chemotherapy with gemcitabine (1000 mg/m² over 30 minutes) as standard palliative treatment. 1

• FOLFIRINOX is superior for fit patients (age ≤75 years, performance status 0-1, bilirubin ≤1.5× upper limit of normal) and significantly improves overall survival. 1, 2
• Gemcitabine plus erlotinib can be considered, but continue erlotinib only if patients develop rash. 1

Metastatic Disease (Stage IV)

FOLFIRINOX is first-line for fit patients; gemcitabine monotherapy is a reasonable alternative for those who cannot tolerate intensive regimens. 2

• Obtain molecular testing: KRAS, BRCA1/2, PALB2, MSI status, and NTRK fusions. 2
• Consider platinum therapy for BRCA1, BRCA2, or PALB2 mutations. 2

Age and Comorbidity Considerations

Elderly patients benefit from radical surgery, but comorbidity becomes the critical limiting factor, especially in patients >75-80 years. 1, 5 Age alone is NOT a contraindication to surgery. 1, 5

Post-Treatment Surveillance

• Monitor CA 19-9 every 3 months for 2 years if preoperatively elevated. 2, 3
• Post-resection CA 19-9 level is an established prognostic marker. 1, 5
• Use CA 19-9 to assess treatment response during chemotherapy. 2, 3

Critical Reporting Requirements

Radiology reports must include: tumor size (whether ≤2 cm), location, vascular involvement using standardized terminology (abutment for <180° involvement, encasement for >180°), lymph node status, and metastatic disease assessment. 1 Structured reporting improves surgical planning accessibility (60-98% vs 32-54% for unstructured reports). 1