What are the management options for pancreatic adenocarcinoma?

Management of Pancreatic Adenocarcinoma

Radical surgery is the only curative treatment for pancreatic adenocarcinoma, primarily suitable for patients with early stage disease (stage I and some stage II), followed by adjuvant chemotherapy to improve survival. 1

Diagnosis and Staging

Initial Evaluation

• Abdominal ultrasound is useful for initial examination
• Further evaluation requires:
  • EUS (endoscopic ultrasound)
  • Contrast-enhanced MD-CT with pancreatic protocol (triphasic cross-sectional imaging with thin 3mm slices)
  • MRI combined with MRCP (magnetic resonance cholangiopancreatography) 1
• Baseline CA19-9 should be obtained (prognostic value in absence of cholestasis) 1

Biopsy Considerations

• For resectable disease, biopsy is not obligatory before surgery
• EUS-guided FNA is preferred over CT-guided FNA when biopsy is needed
• Percutaneous sampling should be avoided in potentially resectable disease due to risk of peritoneal seeding 1

Staging Procedures

• TNM staging system by AJCC-UICC is standard
• MD-CT of chest recommended to evaluate potential lung metastases
• Diagnostic laparoscopy may be beneficial before resection for:
  • Left-sided large tumors
  • High CA19-9 levels
  • When neoadjuvant treatment is considered 1
• PET scan is not routinely recommended for staging 1

Treatment Approach by Stage

Resectable Disease (Stage I and some Stage II)

1. Surgical Management:

   • Pancreatic head tumors: Partial pancreaticoduodenectomy (Whipple procedure)
   • Pancreatic body/tail tumors: Distal pancreatectomy (typically includes splenectomy)
   • Total pancreatectomy in selected cases 1
   • Surgeries should be performed at high-volume centers (15-20 pancreatic resections annually) 1

2. Adjuvant Therapy:

   • 6 months of gemcitabine or 5-FU chemotherapy post-surgery
   • FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) is now preferred with median overall survival of 54.4 months versus 35 months for gemcitabine 1, 2
   • Adjuvant therapy benefits patients even after R1 resection 1

Borderline Resectable Disease

• Neoadjuvant chemotherapy or chemoradiotherapy to downsize tumor
• Re-evaluation for surgical resection after treatment
• Patients who develop metastases during neoadjuvant therapy are not candidates for surgery 1

Locally Advanced Unresectable Disease

• Gemcitabine in conventional dosing (1000 mg/m² over 30 min)
• Consider chemoradiotherapy for local control
• Palliative measures for symptom management 1, 2

Metastatic Disease

• First-line options:
  • FOLFIRINOX for patients ≤75 years with good performance status (0-1) and bilirubin ≤1.5 ULN
  • Gemcitabine alone or with erlotinib (continue erlotinib only if skin rash develops within first 8 weeks)
• Second-line options:
  • After gemcitabine failure: 5-FU and oxaliplatin
  • After FOLFIRINOX failure: Gemcitabine 1, 2
• For BRCA-positive patients: Consider olaparib maintenance after platinum-based therapy 2

Palliative Management

Biliary Obstruction

• Endoscopic stenting is preferred for unresectable patients
• Metal prostheses for patients with life expectancy >3 months
• Percutaneous transhepatic biliary drainage when endoscopic treatment not possible 1

Gastric Outlet Obstruction

• Pro-kinetics like metoclopramide to improve gastric emptying
• Expandable metal stent for duodenal obstruction 1

Pain Management

• Opioids (morphine typically first choice) via oral route when possible
• Percutaneous or EUS-guided celiac plexus blockade for patients with poor opioid tolerance
• Consider hypofractionated radiotherapy for pain control 1

Response Evaluation and Follow-up

During Palliative Treatment

• Evaluate toxicity at each chemotherapy cycle
• Assess response every 8 weeks
• Monitor for ascites during abdominal ultrasound (may indicate peritoneal disease) 1

Post-Surgical Follow-up

• CA19-9 assessment every 3 months for 2 years (if elevated preoperatively)
• Abdominal CT scan every 6 months 1

Common Pitfalls and Caveats

• Avoid percutaneous biopsy in potentially resectable disease due to risk of tumor seeding
• Do not delay surgical resection when clinical suspicion is high despite non-diagnostic biopsy
• Extended lymphadenectomy shows no benefit over standard lymphadenectomy
• Intraoperative radiotherapy remains experimental and is not recommended for routine use
• Combinations of gemcitabine with other cytotoxic agents (except erlotinib) do not significantly improve survival in metastatic disease 1