What is the standard treatment for pancreatic cancer?

Standard Treatment for Pancreatic Cancer

The standard treatment for pancreatic cancer follows a stage-based approach, with surgical resection being the only curative option for early-stage disease, followed by adjuvant chemotherapy, while locally advanced and metastatic disease are primarily treated with systemic chemotherapy regimens such as FOLFIRINOX or gemcitabine-based therapy. 1, 2

Diagnosis and Staging

• Initial evaluation typically begins with abdominal ultrasound to identify pancreatic masses 1
• Contrast-enhanced multi-detector CT (MD-CT) or MRI with MRCP using a triphasic pancreas protocol with thin slices (3mm) is the preferred imaging modality for definitive diagnosis and staging 1
• Endoscopic ultrasound (EUS) complements staging by providing information on vessel invasion and lymph node involvement, and allows for tissue sampling via fine needle aspiration 1, 2
• MD-CT of the chest is recommended to evaluate potential lung metastases 2, 1
• Laparoscopy may detect small peritoneal and liver metastases, changing therapeutic strategy in up to 25% of patients, especially for left-sided large tumors or when neoadjuvant treatment is planned 2

Treatment by Stage

Resectable Disease (Stage I and some Stage II)

• Surgical resection is the only curative treatment option for early-stage pancreatic cancer 2, 1
• For pancreatic head tumors, partial pancreaticoduodenectomy (Whipple procedure) is the treatment of choice 2
• For pancreatic body/tail tumors, distal pancreatectomy (typically including splenectomy) is recommended 2
• Standard lymphadenectomy should be performed; extended lymphadenectomy has not shown benefit 2
• Postoperatively, 6 months of adjuvant chemotherapy with gemcitabine or 5-FU is recommended 2
• The FOLFIRINOX regimen in the adjuvant setting has shown improved survival (median overall survival of 54.4 months compared with 35 months for gemcitabine) 3

Borderline Resectable Disease

• Neoadjuvant chemotherapy or chemoradiotherapy is recommended to potentially downsize tumors and convert them to resectable status 2, 1
• Patients who develop metastases during neoadjuvant therapy are not candidates for subsequent surgery 2
• This approach is particularly beneficial for larger tumors and/or those with vessel encasement 1

Locally Advanced Unresectable Disease

• Gemcitabine in conventional dosing (1000 mg/m² over 30 min) is the recommended treatment 2
• Gemcitabine is FDA-approved as first-line treatment for locally advanced (nonresectable Stage II or Stage III) pancreatic adenocarcinoma 4
• Systemic therapy followed by radiation is an option for definitive locoregional disease control 3

Metastatic Disease (Stage IV)

• For patients with good performance status (ECOG 0-1), combination chemotherapy regimens such as FOLFIRINOX or Gemcitabine + nab-paclitaxel are recommended 5, 3
• The FOLFIRINOX protocol confers significant improvement in overall survival for patients ≤75 years with good performance status (0-1) and bilirubin ≤1.5 ULN 2
• For patients with moderate performance status (ECOG 2), Gemcitabine + nab-paclitaxel or Gemcitabine monotherapy may be considered 5
• For patients with poor performance status (ECOG 3-4), symptomatic treatment only is recommended 5
• Gemcitabine is FDA-approved for patients previously treated with fluorouracil 4

Palliative Management

• For obstructive jaundice (common in 70-80% of pancreatic head cancers), endoscopic stent placement is preferred over percutaneous insertion 2
• Metal prostheses should be used for patients with life expectancy >3 months as they have fewer complications than plastic stents 2
• For duodenal obstruction, endoscopic placement of expandable metal stents or surgical bypass may be considered 2, 5
• Pain management with opioids is essential, with oral administration typically preferred 2

Important Considerations

• Decisions about diagnostic management and resectability should involve multidisciplinary consultation 1
• Pancreatic resections should be performed at high-volume centers (15-20 resections annually) to improve outcomes 1
• Elderly patients can benefit from radical surgery, but comorbidities may contraindicate resection, especially in patients older than 75-80 years 2, 1
• For the 5-7% of patients with BRCA pathogenic germline variants and metastatic disease, PARP inhibitor maintenance therapy may improve progression-free survival following platinum-based therapy 3
• Bilirubin levels should be below 1.5× ULN before initiating combination chemotherapy 5

Emerging Approaches

• Targeted therapies and immunotherapeutic strategies are being investigated, with promising results in specific genetic subgroups 6
• Neoadjuvant approaches for resectable disease are increasingly being studied in clinical trials 2, 7
• Chemoradiation in the adjuvant setting should only be performed within randomized controlled clinical trials 2