Abstract
Current treatment recommendations for resectable pancreatic cancer support upfront resection and adjuvant therapy. Randomized controlled trials offering comparison with the emerging neoadjuvant approach are lacking. This review aims to compare both treatment strategies for resectable pancreatic cancer. PubMed, MEDLINE, Embase, Cochrane Database and Cochrane Databases were searched for studies comparing neoadjuvant and surgery-first with adjuvant therapy for resectable pancreatic cancer. A Bayesian network meta-analysis was conducted using the Markov chain Monte Carlo method. Cochrane Collaboration’s risk of bias, ROBINS-I and GRADE tools were used to assess quality and risk of bias of included trials. 9 studies compared neoadjuvant therapy and surgery-first with adjuvant therapy (n = 22,285). Aggregate rate (AR) of R0 resection for neoadjuvant therapy was 0.8008 (0.3636–0.9144) versus 0.7515 (0.2026–0.8611) odds ratio (O.R.) 1.27 (95% CI 0.60–1.96). 1-year survival AR for neoadjuvant therapy was 0.7969 (0.6061–0.9500) versus 0.7481 (0.4848–0.8500) O.R. 1.38 (95% CI 0.69–2.96). 2-year survival AR for neoadjuvant therapy was 0.5178 (0.3000–0.5970) versus 0.5131 (0.2727–0.5346) O.R. 1.26 (95% CI 0.94–1.74). 5-year AR survival for neoadjuvant therapy was 0.2069 (0.0323–0.3300) versus 0.1783 (0.0606–0.2300) O.R. 1.19 (95% CI 0.65–1.73). In conclusion neoadjuvant therapy may offer benefit over surgery-first and adjuvant therapy. However, further randomized controlled trials are needed.
Highlights
Pancreatic cancer (PC) is the fourth and fifth most common cause of cancer deaths in the USA and Europe respectively[1,2]
Postulated benefits of neoadjuvant therapy (NAT) include: identifying aggressive tumour types avoiding futile surgery, elimination of micrometastesis, increased R0 resection rate and increased rate of completion of multimodal treatment considering that up to 50% of patients treated in surgery first with adjuvant therapy (SFadj) pathway fail to receive adjuvant therapy[5,6,7]
Controversy in the role of NAT for resectable pancreatic cancer (RPC) arises from the potential of loosing the window of resectability[6,7]
Summary
Pancreatic cancer (PC) is the fourth and fifth most common cause of cancer deaths in the USA and Europe respectively[1,2]. In reality most patients develop early recurrence, nullifying the potential benefits of high-risk surgery[4] with up to 50% of patients failing to receive adjuvant therapy due to: post-operative complications, early metastases, reduced performance status and comorbidities[5] This has resulted in the advent of neoadjuvant therapy (NAT) with the postulated benefits of: identifying aggressive tumour avoiding futile surgery, elimination of micrometastesis, increased feasibility of R0 resection and completion of multimodal treatment[6,7]. It has been established that optimal survival outcomes for PC are not obtained by resection alone, but require the delivery of additional treatment whether delivered as neoadjuvant or adjuvant therapy[3,9,10,11,12,13,14,15] Both SFadj and NAT treatment approaches carry the risk of failing to achieve multimodal treatment delivery. Treatment outcomes include: R0 resection rates and 1, 2, 3, 4 and 5-year survival
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