Chemoradiotherapy in the Management of Locally Advanced Pancreatic Carcinoma: A Qualitative Systematic Review

Abstract

Purpose: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At time of diagnosis, 30% of patients present with a locally advanced unresectable but nonmetastatic pancreatic carcinoma (LAPC). The French program Standards, Options, and Recommendations was promoted to conduct a qualitative systematic review to evaluate the role of radiotherapy in patients with LAPC. Methods: A search to identify eligible studies was undertaken using the MEDLINE database. All phase III randomized trials and systematic reviews evaluating the role of radiotherapy in LAPC were included, together with some noncontrolled studies if no phase III trials were retrieved. The quality and clinical relevance of the studies were evaluated using validated checklists, which allowed associating each result with a level of evidence. Results: Twenty-one studies were included, as follows: two meta-analyses, 13 randomized trials, and six nonrandomized trials. Chemoradiotherapy increases overall survival when compared with best supportive care (level of evidence C) or with exclusive radiotherapy (level B1), but is more toxic (level B1). Chemoradiotherapy is not superior to chemotherapy in terms of survival (level B1) and increases toxicity (level A). Recent data favor limited irradiation to the tumor volume (level C). Fluorouracil is still the reference chemotherapy in association with radiotherapy (level B1). Induction chemotherapy before chemoradiotherapy improves survival (level C). Conclusion: No standard treatment exists, but there are two options for treatment of LAPC; these are gemcitabine-based chemotherapy and chemoradiotherapy. Induction chemotherapy followed by a chemoradiotherapy is a promising strategy for selection of patients without early metastatic/progressing disease.