Role of Neoadjuvant Therapy in the Management of Pancreatic Cancer: Is the Era of Biomarker-Directed Therapy Here?

Abstract

Pancreatic cancer is the 4th leading cause of cancerrelated death. Complete surgical resection (CR0) is considered the only curative treatment. Most patients present with unresectable or borderline resectable disease. Many small phase i/ii trials have tried to address the role of neoadjuvant treatment using chemotherapy with or without chemoradiation in the management of locally advanced disease. However, many of them looked at the rate of CR0 resection and the feasibility of such treatment. A trend for improved overall survival has been observed in the group of patients with borderline resectable disease who completed neoadjuvant treatment. A large proportion of patients progress while on treatment, sparing them from unnecessary surgery. We searched the PubMed database (using the key words “pancreatic cancer,” or “pancreatic neoplasm,” or “pancreatic adenocarcinoma,” and “neoadjuvant treatment,” or “neoadjuvant chemotherapy,” or “neoadjuvant radiation therapy,” or “neoadjuvant chemoradiation,” or “adjuvant therapy” [all fields] and “clinical trial” or “study”) and abstracts presented at the American Society of Clinical Oncology meetings on gastrointestinal cancers. Here, we review the most recent papers that present results on neoadjuvant therapy in pancreatic cancer. All but one report used overall survival as an endpoint. Unfortunately, there are no valid biomarkers predicting tumour progression or recurrence, and response to treatment than can help to guide therapeutic choices. Our recommendation is to consider neoadjuvant treatment in cases of borderline resectable disease. In patients with primary resectable tumours, surgery followed by adjuvant treatment and enrollment on adjuvant treatment studies would be appropriate.

Combination of interferon-expressing oncolytic adenovirus with chemotherapy and radiation is highly synergistic in hamster model of pancreatic cancer

“…Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States [ 1 ]. Unfortunately, many patients are found to have advanced disease at the time of diagnosis and are not candidates for surgical resection.…”

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014

“…Most trials were phase ii investigations with small numbers of patients and varying primary endpoints 53 . However, a subset patients were converted to resectability after neoadjuvant therapy 53,54 , and so management of patients with borderlineresectable pcc should be discussed at multidisciplinary tumour boards. Trial referral is advisable when appropriate 53 .…”

Neoadjuvant Chemoradiation Therapy is Associated with Adverse Outcomes in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Cancer

“…In a singleinstitution case-matched analysis, patients with initial borderline or locally advanced pancreatic cancers who underwent pancreatectomy after neoadjuvant chemoradiation were compared with initially resected patients. 8,17,18 Another study matched patients with locally advanced pancreatic adenocarcinoma who had been treated with preoperative chemotherapy with control patients who underwent operation as their primary treatment modality. 19 They found no significant difference in postoperative morbidity or mortality rates or in rates of pancreatic fistulae.…”