Neoadjuvant vs Upfront Surgery for Resectable Pancreatic Cancer and Periampullary Cancer

Pancreatic cancer is the seventh highest cause of death from cancer worldwide, with only 20% of patients presenting with resectable disease. Despite potentially curative resections, 5-year survival remains at 20%. This study evaluates whether neoadjuvant chemotherapy can improve outcomes by eliminating occult metastatic disease and improving resection margins.

Patients with clearly resectable pancreatic head cancer or periampullary cancer will be randomized 1:1 to either neoadjuvant chemotherapy followed by open or laparoscopic pancreaticoduodenectomy (Arm A) or upfront laparoscopic pancreaticoduodenectomy followed by adjuvant chemotherapy (Arm B). The primary endpoint is overall survival, with secondary endpoints including R0 resection rate , disease-free survival and perioperative outcomes.

Inclusion criteria

• Histologically or cytologically confirmed pancreatic head cancer or periampullary carcinoma(endoscopic ultrasound (EUS)-guided biopsy).
• Clearly resectable disease as defined by National Comprehensive Cancer Network (NCCN) criteria on cross-sectional imaging:

No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery .

Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence No evidence of metastatic disease.

• Eastern Cooperative Oncology Group (ECOG)=0-1 & American Society of Anesthesiologists (ASA) score <4.
• Written informed consent.
• Medical history without previous pancreatic resection or pancreatic cancer.
• Adequate organ function (liver, kidney, bone marrow) (serum creatinine ≤2.0 mg/dL,reference range 0.5-1.20 mg/dL; serum albumin ≥2.5 g/dL, reference range 3.5-5.3; aspartate aminotransferase (AST) ≤95 U/L, reference range 0-38; Alanine aminotransferase (ALT) ≤102 U/L, reference range 0-41; prothrombin time ≤1.8, reference range 0-1.20; partial thromboplastin time ≤1.8, reference range 0.82-1.25; leukocyte count greater than 3.5×109/L, reference range 4.2-9.0; platelet count greater than 100×109/L, reference range 130-400; hemoglobin ≥9 g/dL, reference range 12-16).

Exclusion criteria

• Borderline resectable or locally advanced pancreatic or periampullary cancer.
• Tumor at the body or tail of the pancreas.
• Distant metastases.
• Prior chemotherapy , surgery or radiotherapy for pancreatic cancer.
• Severe comorbidities precluding surgery or chemotherapy.
• Pregnancy or lactation.
• Other neoplastic diseases (malignant)diagnosed in the past 5 years.
• Major surgery or traumatic event in the past 28 days.