Neoadjuvant Treatment vs Upfront Surgery for Left-Sided Pancreatic Cancer

Pancreatic cancer is one of the most treatment resistant malignancies, often diagnosed at a late stage and associated with poor survival. The 5-year overall survival rate remains around 10%. Prognosis is affected by multiple factors including tumor stage, biology, treatment response, and anatomical location. Distal (left-sided) pancreatic cancer, originating from the body or tail of the pancreas, accounts for approximately 20-25% of all pancreatic cancers and has been associated with worse survival than pancreatic head cancer, even when adjusted for stage. This may be due to histological, molecular, and embryological differences, and varied systemic therapy responses.

Neoadjuvant chemotherapy has become increasingly important in managing pancreatic cancer. It may improve outcomes by reducing tumor size, allowing for more complete (R0) resections, treating micrometastatic disease early, and identifying patients unlikely to benefit from surgery. While neoadjuvant therapy is recommended for borderline resectable and locally advanced tumors, randomized trials have not shown benefit for patients with upfront resectable pancreatic head cancer. Importantly, no randomized controlled trials have investigated the benefit of neoadjuvant treatment specifically in patients with upfront resectable left-sided pancreatic cancer, despite its distinct biology and worse prognosis.

Retrospective data suggest neoadjuvant therapy may improve survival in left-sided tumors. A recent multicenter study reported significantly longer overall survival in patients treated with neoadjuvant therapy compared to upfront surgery alone. However, prospective randomized data are lacking.

This multicenter randomized trial aims to assess whether patients with resectable left-sided pancreatic cancer benefit from neoadjuvant chemotherapy compared to upfront surgery. The study will reflect real-world clinical practice by allowing both commonly used regimens-FOLFIRINOX and Gemcitaine-Nab-paclitaxel -as neoadjuvant options. Previous studies have shown these regimens to be similarly effective, and switching between them due to toxicity or progression is feasible and does not seem to impair surgical outcomes or survival. This study aims to evaluate the benefits of neoadjuvant chemotherapy before surgery in a prospective multicenter randomized setting for resectable left-sided pancreatic cancer patients.