What is the recommended evaluation and treatment approach for pancreatic cancer?

Evaluation and Treatment Approach for Pancreatic Cancer

The recommended evaluation for pancreatic cancer includes initial abdominal ultrasound followed by contrast-enhanced MD-CT and MRI with MRCP for diagnosis, with EUS for complementary staging and biopsy when needed, while treatment involves radical surgery for resectable disease (stages I and some II) followed by 6 months of gemcitabine or 5-FU chemotherapy. 1

Diagnosis and Initial Evaluation

Initial Assessment

• Abdominal ultrasound is useful for initial examination 1
• For further evaluation, the following modalities are recommended:
  • Contrast-enhanced multi-detector CT (MD-CT) - highest sensitivity (95%) and specificity (93%) 1, 2
  • MRI with MRCP - provides detailed ductal images without ERCP-induced pancreatitis risk 1, 2
  • Endoscopic ultrasound (EUS) - highly sensitive (79-81%) for detecting small tumors and vascular invasion 1, 2

Biopsy Considerations

• For patients who will undergo surgery with radical intent, a previous biopsy is not obligatory 1
• Biopsy should be restricted to cases where imaging results are ambiguous 1
• EUS-guided biopsy is preferred; percutaneous sampling should be avoided to prevent tumor seeding 1
• Metastatic lesions can be biopsied percutaneously under ultrasound or CT guidance or during EUS 1

Important Diagnostic Pitfalls

1. PET scan has no role in the diagnosis of pancreatic cancer and does not allow reliable differentiation between chronic pancreatitis and pancreatic cancer 1, 3
2. In the preoperative setting, ERCP and biliary stenting should only be performed if surgery cannot be done expeditiously, as it increases serious complications 1
3. Baseline CA19.9 can be used to guide treatment and follow-up but has limited diagnostic value due to lack of specificity and false elevations in cholestasis 1

Staging

Recommended Staging Approach

• The established staging system is the TNM system developed by the AJCC-UICC 1
• MD-CT or MRI plus MRCP should be used for primary staging 1
• EUS complements staging by providing information on vessel invasion and lymph node involvement 1
• MD-CT of the chest is recommended to evaluate potential lung metastases 1
• Laparoscopy may detect small peritoneal and liver metastases in <15% of patients and should be considered before resection in left-sided large tumors and/or with high CA19.9 levels 1

Resectability Assessment

• To be resectable, tumors must show no evidence of:
  • Extra-pancreatic disease
  • Direct tumor extension to the celiac axis and superior mesenteric artery
  • Non-obstructive invasion of the superior mesenteric-portal vein confluence 1
• Less than 20% of all patients have resectable disease at diagnosis 1, 4

Treatment

Resectable Disease (Stage I and some Stage II)

• Radical surgery is the only curative treatment 1
• Surgical approach depends on tumor location:
  • Pancreatic head tumors: partial pancreatico-duodenectomy 1
  • Pancreatic body/tail tumors: distal resection of the pancreas 1
  • Some cases may require total pancreatectomy 1
• Standard lymphadenectomy should be performed; extended lymphadenectomy shows no benefit 1
• Postoperatively, 6 months of gemcitabine or 5-FU chemotherapy is recommended 1
• Patients benefit from adjuvant chemotherapy even after R1 resection 1
• For resectable disease, FOLFIRINOX has shown superior survival outcomes (54.4 months) compared to single-agent gemcitabine (35 months) 4

Borderline Resectable Disease

• Neoadjuvant chemotherapy or chemoradiotherapy may achieve downsizing of the tumor and convert it to resectable status 1
• Patients who develop metastases during neoadjuvant therapy are not candidates for surgery 1

Locally Advanced/Metastatic Disease

• Gemcitabine is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas 5
• Multiagent chemotherapy regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel) provide survival benefit of 2-6 months compared to single-agent gemcitabine 4
• For patients with BRCA pathogenic germline variants (5-7% of cases), olaparib maintenance therapy improves progression-free survival following initial platinum-based therapy 4

Management of Complications

• Biliary obstruction: ERCP has a role only to relieve bile duct obstruction 1
• Endoscopic stent placement is recommended for biliary obstruction:
  • Plastic stents for patients planned for surgery
  • Self-expanding metal stents for patients expected to survive >3 months 2
• Duodenal obstruction: Surgical bypass or endoscopic duodenal stenting is recommended 2

Screening and Surveillance

• No efficient screening tools are available for the general population 1
• For high-risk individuals (those with hereditary conditions), regular EUS and MRI are recommended 1, 2
• Risk factors requiring consideration for screening include:
  • Family history of pancreatic cancer
  • Genetic syndromes
  • Chronic pancreatitis
  • Recent-onset diabetes
  • Tobacco use
  • Obesity
  • High consumption of processed meat 2

By following this comprehensive approach to evaluation and treatment, clinicians can optimize outcomes for patients with pancreatic cancer, though the overall prognosis remains poor with >95% of those affected dying of their disease 1.