What are the management options for pancreatic cancer (Pancreatic CA)?

Management of Pancreatic Cancer

The management of pancreatic cancer requires a multidisciplinary approach with treatment strategies determined by disease stage, with radical surgery being the only curative option for early-stage disease (stages I and II), while chemotherapy regimens like FOLFIRINOX or gemcitabine plus nab-paclitaxel are recommended for metastatic disease based on patient performance status. 1, 2

Diagnosis and Staging

• CT scan with pancreatic protocol is the preferred initial imaging modality for diagnosis and staging, providing essential information about tumor extent and vascular involvement 2
• Endoscopic ultrasound (EUS) is valuable for assessing vascular invasion and obtaining tissue samples when needed, with EUS-guided biopsy preferred over percutaneous sampling 1
• Staging laparoscopy should be considered before resection in left-sided large tumors or when neoadjuvant treatment is planned, as it can detect occult metastases in up to 15-25% of patients 1
• The TNM staging system developed by AJCC-UICC is the established standard, but practical staging often relies on resectability criteria (resectable, locally advanced-unresectable, or metastatic) 1, 2

Treatment by Stage

Resectable Disease (Stage I and some Stage II)

• Radical surgical resection is the only potentially curative treatment option 1, 3
• For pancreatic head tumors, pylorus-preserving pancreaticoduodenectomy is the procedure of choice 1
• For tumors of the pancreatic body or tail, distal pancreatectomy (typically including splenectomy) is standard 1
• Postoperative adjuvant chemotherapy with either gemcitabine or 5-fluorouracil for 6 months is recommended to improve survival 1
• Despite complete resection, 5-year overall survival remains only 10-20%, with long-term survival in lymph node-positive tumors being rare 1, 3

Borderline Resectable Disease

• Neoadjuvant chemotherapy or chemoradiotherapy should be considered to achieve tumor downsizing and potentially convert unresectable tumors to resectable status 1, 2
• Patients who develop metastases during neoadjuvant therapy are not candidates for secondary surgery 1
• Multidisciplinary consultation is essential to determine resectability 4

Locally Advanced Unresectable Disease

• Gemcitabine in conventional dosing (1000 mg/m² over 30 minutes) is recommended for patients with unresectable tumors 1, 5
• Chemoradiation may be considered for local control after initial systemic therapy 6
• Surgery may still be considered for palliative purposes to relieve symptoms such as biliary or gastric outlet obstruction 1

Metastatic Disease (Stage IV)

• FOLFIRINOX is recommended for patients with ECOG PS 0-1, favorable comorbidity profile, and adequate support systems, showing median overall survival of 11.1 months versus 6.8 months with gemcitabine alone 1
• Gemcitabine plus nab-paclitaxel is recommended for patients with ECOG PS 0-1 and relatively favorable comorbidity profile, with median overall survival of 8.5 months versus 6.7 months with gemcitabine alone 1
• Gemcitabine monotherapy is recommended for patients with ECOG PS 2 or prohibitive comorbidities, with the option to add capecitabine or erlotinib 1
• For patients with ECOG PS ≥3 or poorly controlled comorbidities, cancer-directed therapy should be considered only on a case-by-case basis 1

Palliative Care

• Optimal symptom management is crucial in metastatic disease 1
• For biliary obstruction, endoscopic stent placement is preferred over percutaneous insertion, with metal stents recommended for patients with life expectancy >3 months 1, 2
• Pain management should follow standard guidelines, with consideration of radiotherapy for coeliac pain control 2
• Nutritional support and management of thromboembolic disease are important aspects of comprehensive care 4, 7

Important Considerations

• Pancreatic resections should be performed at high-volume centers (>15 procedures annually) to improve outcomes 4
• Clinical trials should be discussed with all patients at all stages of disease 1
• For the 5-7% of patients with BRCA pathogenic germline variants and metastatic disease, maintenance therapy with PARP inhibitors may improve progression-free survival after initial platinum-based therapy 6
• Early implementation of palliative care can improve quality of life and potentially survival 7

Prognosis

• Despite advances in treatment, pancreatic cancer remains highly lethal with poor long-term survival 3, 6
• Only 10-15% of patients present with resectable disease at diagnosis 6
• Even with complete resection and adjuvant therapy, 5-year survival rates remain low at 10-20% 3, 4
• The incidence of pancreatic cancer is increasing and is projected to become the second leading cause of cancer-related mortality by 2030 6