Neoadjuvant Therapy in Resectable Pancreatic Cancer

Is This the Way Forward? A Narrative Review

Giampaolo Perri; Giovanni Marchegiani; Giuseppe Malleo; Roberto Salvia


Chin Clin Oncol. 2021;10(5):47 

In This Article

Abstract and Introduction


Background: Pancreatic cancer represents a systemic disease, and its treatment ideally includes the administration of systemic therapy regardless of its anatomical stage.

Methods: In this brief narrative review, the most recent literature will be highlighted, together with updates, new perspectives on the topic, and the authors own personal view.

Results: While preoperative therapy has recently become the new standard for borderline resectable stages, adjuvant therapy after surgery remains the current standard of care for resectable disease. However, to deliver systemic therapy in the postoperative setting implies that a significant subset of patients, not fully recovering after a pancreatectomy, will never receive appropriate treatment. Administration of chemotherapy before pancreatectomy may represent the only way to assure optimal treatment, simultaneously selecting patients for surgery according to tumor biology. For these reasons, many high-volume centers for pancreatic surgical oncology are increasingly considering this strategy also for patients with resectable disease.

Conclusions: Nonetheless, available data to support this paradigm shift are still germinal, and the optimal modalities and timing of preoperative therapy are eagerly debated as well.


Pancreatic ductal adenocarcinoma (PDAC) has recently become the 3rd cause of cancer-related mortality in the United States.[1] PDAC remains associated with a dismal prognosis, considering that the 5-year overall survival is still of less than 8%[2] and approximately two-third of the patients present with metastatic—therefore inoperable—disease. Primary oncologic resection, the only potentially curative treatment, is consequently possible in less than 20% of patients. When the disease is localized to the pancreas, PDAC can be classified as resectable, borderline resectable, or locally advanced (unresectable).[3] In all patients undergoing surgery, systemic therapy is considered ideal for optimizing outcomes. It dramatically improves survival outcomes, and is classically administered in the adjuvant setting as the standard of care.[4,5] Recently, with the intent of better selection, and to increase the number of potential candidates for surgery, the treatment paradigm has rapidly evolved towards preoperative treatment strategies (Figure 1). Nowadays, preoperative therapy has become the new standard for borderline resectable PDAC, according to expert opinions and consensus statements.[3,6] However, available data to support preoperative therapy in resectable stages are still germinal, and the optimal sequence of systemic and surgical treatment is eagerly debated. In this brief narrative review, the most recent literature will be highlighted together with updates, new perspectives on the topic, and authors own personal views and opinions. We present the following article in accordance with the Narrative Review reporting checklist (available at

Figure 1.

Authors proposal for algorithms of treatment strategies (including preoperative therapy only; adjuvant therapy only, or both) and outcome parameters for resectable pancreatic cancer. CT, computed tomography; MRI, magnetic resonance imaging; CA 19–9, carbohydrate antigen 19.9; CEA, carcinoembryonic antigen; FOLFIRINOX, folinic acid, 5-fluorouracil, irinotecan, oxaliplatin; R0/1, negative/microscopically positive tumor margins.