Abstract
Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4–6 months induction chemotherapy, the majority of patients have stable disease or even tumor-regression. Of these, 12 to 35% are successfully downstaged to resectable disease. Several studies have reported a 30–35 months overall survival after resection; although it currently remains unclear if this is a result of the resection or the good response to chemotherapy. Following chemotherapy, selection of patients for resection is difficult, as contrast-enhanced computed-tomography (CT) scan is unreliable in differentiating between viable tumor and fibrosis. In case a resection is not considered possible but stable disease is observed, local ablative techniques are being studied, such as irreversible electroporation, radiofrequency ablation, and stereotactic body radiation therapy. Pragmatic, multicenter, randomized studies will ultimately have to confirm the exact role of both surgical exploration and ablation in these patients. Since evidence-based guidelines for the management of LAPC are lacking, this review proposes a standardized approach for the treatment of LAPC based on the best available evidence.
Highlights
Pancreatic cancer is diagnosed some 340,000 times per year globally [1] and carries a 5 year cumulative survival of 5–10% [2]
Staging of pancreatic cancer is usually performed using high quality CT imaging according to the National Comprehensive Cancer Network (NCCN) criteria [15], but may vary depending on local standards
According to the NCCN criteria, Locally advanced pancreatic cancer (LAPC) is defined as a pancreatic adenocarcinoma without overt distant metastases, with >180◦ involvement of the hepatic artery, superior mesenteric artery and/or celiac trunk, or unreconstructible involvement of the porto-mesenteric vein
Summary
Pancreatic cancer is diagnosed some 340,000 times per year globally [1] and carries a 5 year cumulative survival of 5–10% [2]. 15–20% of patients have resectable pancreatic cancer at diagnosis and are treated with a combination of surgery and (neo)adjuvant chemotherapy. The remaining patients present with either metastatic disease (40–50%) or locally advanced, nonresectable pancreatic cancer (LAPC) due to local but extensive vascular involvement (30–40%) [3,4]. The introduction of FOLFIRINOX (a combination therapy of leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin), which on itself has led to an improvement of median overall survival from 9 to 16 months [5], and to the possibility to convert LAPC to resectable disease in 10–35% of patients [6,7,8]. Randomized trials are needed to confirm the benefit of surgery after FOLFIRINOX, several nonrandomized cohort studies reported a survival of 30–34 months from diagnosis for patients undergoing resection after FOLFIRINOX [9]
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