Comparison of neoadjuvant regimens for resectable gastroesophageal junction cancer: a systematic review of randomized clinical trials across three decades

Abstract

Background: The optimal perioperative treatment for adenocarcinoma of gastroesophageal junction (GEJ) tumor remains uncertain. The systematic review aims to assess the best neoadjuvant modality, namely chemotherapy (CT) versus chemoradiotherapy (CRT) based on randomized controlled trials (RCTs) for resectable gastric, esophageal and GEJ tumors. Methods:We performed a comprehensive PubMed database and Cochrane Library search to identify relevant RCTs related to neoadjuvant treatment for resectable GEJ adenocarcinoma. We included all published RCTs (phase 2 or 3) that tested specific neoadjuvant therapies (CT or CRT) if the patient population included GEJ tumors. We applied the Version 2 Cochrane risk-of-bias tool (RoB 2) to all the eligible studies. Outcomes examined included R0 resection and pathological response based on intention-totreat (ITT) analysis, surgical outcomes, notable adverse events, and overall survival (OS). Each randomized group of every study was noted to be neoadjuvant CRT, CT, or surgery alone in order to compare the outcomes among these treatment approaches.Results: We identified 25 RCTs with 7,855 patients published from 1996 to 2019. Seven studies tested preoperative CT versus surgery alone, 7 tested preoperative radiotherapy (RT) or CRT versus surgery alone, 4 tested preoperative RT or CRT versus preoperative CT, and 7 tested other combinations. The R0 resection ranged 47-100% and the 3-year OS ranged 6-66.1% in all the study arms. In an exploratory analysis, CRT strategies showed a superior R0 resection rate [80.

Minimally invasive surgery for gastro-oesophageal junction adenocarcinoma: Current evidence and future perspectives

“…Another study showed that preoperative radiochemotherapy determined improvement in R0 resection rate, compared to surgery and preoperative chemotherapy, but there is no significant difference in OS. Both neoadjuvant strategies remain clinically meaningful options for patients with resectable gastroesophageal junction tumors[ 105 , 106 ].…”

A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Patients with Esophageal Adenocarcinoma

“…Of the patients,42% did not undergo surgery after neoadjuvant chemoradiation (28% due to the progression of the disease), which is similar to the published literature. A systematic review of 25 randomized clinical trials reported up to 38% of patients who were not offered surgery in an intention-to-treat analysis 31 …”

“…A systematic review of 25 randomized clinical trials reported up to 38% of patients who were not offered surgery in an intention-to-treat analysis. 31 The limitations of our study include the lack of a cohort of patients treated with surgical resection as their primary treatment. Analysis of this cohort's tissue mesothelin expression as it relates to OS could have provided better context to our observations and given credence to using treatment naïve tissue mesothelin expression as a prognostic factor for survival.…”