Upfront Surgery versus Neoadjuvant Therapy for Resectable Pancreatic Cancer: Systematic Review and Bayesian Network Meta-analysis

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.

Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Meta-Analysis of Randomized Controlled Trials

“…Until recently, only two small randomized controlled trials (RCTs) had been performed comparing SF to NT, and both were terminated early due to poor accrual [21,22]. Previous systematic reviews and meta-analyses that have purported a survival benefit with NT included non-randomized prospective and retrospective studies, which are limited due to their inherent selection biases [14,[23][24][25][26]. As several larger RCTs have recently been completed, albeit with older neoadjuvant regimens, the purpose of the current study was to perform a meta-analysis limited to only RCTs evaluating SF vs. NT for PDAC.…”

Neoadjuvant therapy in pancreatic cancer: what is the true oncological benefit?

“…Therefore, for early-stage, i.e., resectable, PCa, there is not enough scientific evidence for routinely recommending neoTx [7]. NeoTx in resectable PCa remains area of controversy and awaits the results of ongoing RCTs [21].…”

Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis

“…While upfront surgery followed by adjuvant therapy has been the standard of care for PDAC, this is being challenged by recent evidence with use of neoadjuvant chemotherapy (NAT) for borderline resectable pancreatic cancer (BRPC) [ 6 ] and resectable (RPC) [ 7 ] pancreatic cancer (LAPC) [ 8 ]. It is important to determine the impact of different treatment strategies on pattern of disease recurrence [ 9 , 10 ]. NAT is associated with a higher rate of achieving R0 margins [ 11 , 12 ] and may control micrometastatic disease; thus, it is important to determine whether NAT influences patterns of treatment failure in terms of the frequency and site of recurrent cancer.…”