What is the step-wise approach to treating pancreatic cancer?

Step-wise Approach to Pancreatic Cancer Treatment

The primary treatment approach for pancreatic cancer is achieving R0 resection (negative margins) through appropriate surgical intervention based on tumor location, followed by 6 months of adjuvant chemotherapy with either gemcitabine or 5-fluorouracil to improve survival. 1

Diagnosis and Staging

• Imaging studies:

  • Specialized pancreatic CT or MRI with thin slices (3mm) and multi-phase imaging technique 2
  • Endoscopic ultrasound (EUS) as complementary to CT for staging 2
  • MD-CT of chest to evaluate potential lung metastases 1

• Tissue diagnosis:

  • EUS-directed FNA biopsy is preferable to CT-guided FNA for better diagnostic yield and safety 2
  • Pathological diagnosis according to WHO classification from biopsy or fine needle aspiration 2

• Additional staging procedures:

  • Diagnostic laparoscopy to rule out subradiologic metastases (especially for body and tail lesions) 2
  • Laparoscopy for large left-sided tumors to detect small peritoneal or liver metastases 1

Treatment Based on Disease Stage

1. Resectable Disease (10-15% of patients)

• Surgical approach:

  • For pancreatic head tumors: Pylorus-preserving pancreaticoduodenectomy or modified Whipple procedure 1
  • For pancreatic body/tail tumors: Distal pancreatectomy with splenectomy 1
  • Standard lymphadenectomy should include specific lymph node dissection 1
  • Resections should be performed at institutions that perform at least 15-20 pancreatic resections annually 2

• Adjuvant therapy:

  • 6 months of adjuvant chemotherapy with either gemcitabine or 5-fluorouracil after successful R0 resection 1
  • Gemcitabine is preferred due to fewer side effects 1
  • For R1 resection (microscopic positive margins), a combination of 5-FU and radiotherapy may be considered 1

2. Borderline Resectable Disease

• Neoadjuvant therapy:

  • Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery 3
  • Goal is to downsize the tumor and potentially convert it to resectable status 1

• Re-staging and surgical evaluation:

  • Repeat imaging after neoadjuvant therapy to assess resectability
  • Proceed to surgery if converted to resectable status

3. Locally Advanced Disease (30-35% of patients)

• Primary treatment:

  • Systemic therapy followed by radiation for definitive locoregional disease control 3
  • Gemcitabine has been associated with a small survival benefit compared with bolus 5-fluorouracil 2

• Palliative procedures:

  • Stenting or bypass surgery for obstructive jaundice or gastric outlet obstruction 2
  • Metal prostheses preferred for patients with life expectancy >3 months 2
  • Percutaneous transhepatic biliary drainage when endoscopic treatment is not possible 2

4. Metastatic Disease (50-55% of patients)

• Systemic therapy options:

  • FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) for patients ≤75 years with good performance status 2, 3
  • Gemcitabine alone or in combination with erlotinib (continue erlotinib only if skin rash develops within first 8 weeks) 2, 4
  • Gemcitabine/nab-paclitaxel as an alternative regimen 3

• Second-line therapy:

  • 5-FU and oxaliplatin after first-line gemcitabine 2
  • Gemcitabine after first-line FOLFIRINOX 2

• Pain management:

  • Opioids (morphine typically drug of choice) 2
  • Percutaneous or per-EUS celiacoplexus blockade for patients with poor tolerance to opiates 2
  • Hypofractionated radiotherapy in some cases 2

Follow-up

• For patients after resection:

  • Clinical evaluation 3-12 months after resection 1
  • Subsequent follow-up every 6-12 months with appropriate imaging studies 1
  • If preoperative CA19.9 was elevated, assess this marker every 3 months for 2 years 2
  • Abdominal CT scan every 6 months 2

• For patients on palliative therapy:

  • Follow at each cycle of chemotherapy for toxicity 2
  • Evaluate response to chemotherapy every 8 weeks 2
  • Clinical benefit assessment and ultrasound to monitor disease course 2

Common Pitfalls to Avoid

• Delaying surgery when tumor is resectable 1
• Inadequate lymph node dissection 1
• Omitting adjuvant therapy 1
• Performing extended lymphadenectomy (no proven benefit) 1
• ERCP and biliary stenting preoperatively should only be performed when necessary 1
• Intraoperative radiotherapy (still experimental, not recommended for routine use) 1

This step-wise approach emphasizes early diagnosis, proper staging, and appropriate treatment selection based on disease stage to maximize survival and quality of life for patients with pancreatic cancer.