What is the recommended treatment approach for borderline resectable pancreatic adenocarcinoma?

Treatment Approach for Borderline Resectable Pancreatic Adenocarcinoma

Patients with borderline resectable pancreatic adenocarcinoma should receive neoadjuvant chemotherapy or chemoradiotherapy followed by surgical resection if the disease does not progress during treatment. 1

Definition and Diagnosis

Borderline resectable pancreatic cancer (BRPC) is characterized by:

• Tumor contact with major abdominal vessels (portal vein, superior mesenteric vein, or limited involvement of superior mesenteric artery)
• Technically challenging to achieve R0 resection with upfront surgery
• National Comprehensive Cancer Network (NCCN) criteria should be used for determining resectability status 1

Diagnostic workup should include:

• Multi-detector CT scan or MRI with contrast as the primary imaging modality
• Endoscopic ultrasound (EUS) for tissue diagnosis and assessment of vascular involvement
• Tumor marker CA19-9 assessment

Recommended Treatment Algorithm

Step 1: Neoadjuvant Therapy

• First choice: FOLFIRINOX-based chemotherapy regimen 2

  • Superior outcomes compared to gemcitabine-based regimens
  • Higher rates of R0 resection
  • Independent predictor of improved prognosis

• Alternative options (if patient cannot tolerate FOLFIRINOX):

  • Gemcitabine/albumin-bound paclitaxel 1
  • Gemcitabine-based chemoradiotherapy 1

Step 2: Restaging After Neoadjuvant Therapy

• Repeat CT/MRI imaging after completion of neoadjuvant therapy
• Reassess CA19-9 levels
• Evaluate for:
  • Local disease response
  • Absence of disease progression
  • No development of distant metastases

Step 3: Surgical Resection

• Proceed to surgical exploration if:

  • No disease progression during neoadjuvant treatment 1
  • Patient maintains good performance status
  • No evidence of distant metastases

• Surgical approach:

  • Aim for R0 resection (negative margins) 1
  • Standard lymphadenectomy (not extended) 1
  • Vascular resection and reconstruction if necessary to achieve R0 status

Step 4: Adjuvant Therapy

• Complete a total of 6 months of systemic therapy (including neoadjuvant period)
• Options include:
  • Gemcitabine 1, 3
  • 5-FU/leucovorin 1, 4
  • Gemcitabine/capecitabine 1

Evidence Supporting Neoadjuvant Approach

The neoadjuvant approach for borderline resectable pancreatic cancer is supported by several key advantages:

1. Improved R0 resection rates: Neoadjuvant therapy increases the likelihood of achieving negative surgical margins 5, 2

   • R0 resection rates of 63% with neoadjuvant therapy vs. 31% with upfront surgery 5

2. Early delivery of systemic therapy: Ensures all patients receive systemic treatment, addressing the issue that approximately 50% of patients never receive adjuvant therapy after upfront surgery 5

3. Patient selection benefit: Identifies patients who develop metastases during neoadjuvant treatment, avoiding futile surgery 1

4. Survival advantage: Multiple studies show improved median overall survival with neoadjuvant approach

   • 19 months with neoadjuvant approach vs. 15 months with upfront surgery 5
   • Korean trial showed median OS of 21 vs. 12 months favoring neoadjuvant therapy 5

Important Considerations and Pitfalls

1. Patient selection: Neoadjuvant therapy is most beneficial for patients with good performance status who can tolerate aggressive treatment regimens

2. Biliary drainage: Consider biliary stenting before initiating neoadjuvant therapy if significant biliary obstruction is present

3. Treatment toxicity: Monitor closely for adverse effects during neoadjuvant therapy, particularly with FOLFIRINOX regimen, which may require dose modifications

4. Radiation therapy considerations:

   • Stereotactic body radiation therapy (SBRT) may provide benefits over conventional fractionated radiation therapy 6
   • Should be discontinued if patient deteriorates during treatment 7

5. Surgical timing: Optimal timing for surgery after completion of neoadjuvant therapy is typically 4-6 weeks to allow recovery while not delaying too long

6. Progression during neoadjuvant therapy: Patients who develop metastases or show local progression during neoadjuvant treatment should not proceed to surgery 1

By following this treatment algorithm, patients with borderline resectable pancreatic adenocarcinoma have the best chance for R0 resection and improved survival outcomes.