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

Jordan M Cloyd,Terence Williams,Victor Heh,Mary Dillhoff,John F P Bridges,Heena Santry,Laith Abushahin,Allan Tsung,Aslam Ejaz,Timothy M Pawlik

doi:10.3390/jcm9041129

Jordan M Cloyd, Terence Williams + Show 8 more

Open Access

https://doi.org/10.3390/jcm9041129

Copy DOI

Abstract

The efficacy of neoadjuvant therapy (NT) versus surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC) remains controversial. A random-effects meta-analysis of only prospective randomized controlled trials (RCTs) comparing NT versus SF for potentially resectable (PR) or borderline resectable (BR) PDAC was performed. Among six RCTs including 850 patients, 411 (48.3%) received NT and 439 (51.6%) SF. In all included trials, NT was gemcitabine-based: four using chemoradiation and two chemotherapy alone. Based on an intention-to-treat analysis, NT resulted in improved overall survival (OS) compared to SF (HR 0.73, 95% CI 0.61–0.86). This effect was independent of anatomic classification (PR: hazard ratio (HR) 0.73, 95% CI 0.59–0.91; BR: HR 0.51 95% CI 0.28–0.93) or NT type (chemoradiation: HR 0.77, 95% CI 0.61–0.98; chemotherapy alone: HR 0.68, 95% CI 0.54–0.87). Overall resection rate was similar (risk ratio (RR) 0.93, 95% CI 0.82–1.04, I2 = 39.0%) but NT increased the likelihood of a margin-negative (R0) resection (RR 1.51, 95% CI 1.18–1.93, I2 = 0%) and having negative lymph nodes (RR 2.07, 95% CI 1.47–2.91, I2 = 12.3%). In this meta-analysis of prospective RCTs, NT significantly improved OS in an intention-to-treat fashion, compared with SF for localized PDAC. Randomized controlled trials using contemporary multi-agent chemotherapy will be needed to confirm these findings and to define the optimal NT regimen.

Highlights

Despite recent improvements, pancreatic ductal adenocarcinoma (PDAC) remains a deadly cancer with an overall survival (OS) rate at 5 years of only 10% [1]
TehOeseSfoinfdipnagstireenmtasinweditshignriefisceancttaambloengor borderline resectable PDboAthCpawtiehnots wreitchePivReadndNBRTdwiseaassenanedarwleyre3i0nd%epgenrdeeantteorf tthheatnypethoaf tNoT.fTpheatciuerrnetnst swtuhdyo underwent confirmed improvements in R0 resection rate and lymph node positivity with the use of neoadjuvant therapy (NT) and no difference in overall resection rate. These results represent the strongest evidence to date for NT in the management of localized PDAC
Immediate surgical resection followed by adjuvant chemotherapy has long been the standard treatment for PDAC, and recent trials suggest improving OS for those patients who are able to undergo resection and receive adjuvant therapy [4,5,38]

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) remains a deadly cancer with an overall survival (OS) rate at 5 years of only 10% [1]. Adjuvant chemotherapy following surgery improves OS rates [3,4,5]. A significant proportion of patients are unable to initiate adjuvant chemotherapy following pancreatectomy, frequently because of postoperative complications or rapid disease recurrence [6]; many more are unable to finish the planned course of adjuvant therapy [7]. A strategy of surgery first (SF) followed by planned adjuvant therapy has not resulted in significant improvements in OS during the past several decades, even at high-volume, experienced institutions [8,9]. Neoadjuvant therapy (NT) has been associated with improved rates of margin-negative resection and a decreased incidence of lymph node metastases [10,11]. NT has become the preferred approach for borderline resectable (BR) PDAC, while guidelines support the use of either SF or NT for potentially resectable (PR) PDAC [16,17,18]

Objectives

Methods

Results

Conclusion