Evidence-Based Medicine
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2020; 12(1): 113-123
Published online Jan 15, 2020. doi: 10.4251/wjgo.v12.i1.113
Validity of studies suggesting preoperative chemotherapy for resectable thoracic esophageal cancer: A critical appraisal of randomized trials
Giulia Manzini, Ursula Klotz, Doris Henne-Bruns, Michael Kremer
Giulia Manzini, Ursula Klotz, Doris Henne-Bruns, Michael Kremer, Department of General and Visceral Surgery, University of Ulm, Ulm 89081, Germany
Michael Kremer, Department of General and Visceral Surgery, Hospital of Aarau, Aarau 5000, Switzerland
Author contributions: Manzini G, Klotz U and Henne-Bruns DH contributed substantially to the conception and design of the study; Manzini G and Klotz U contributed to the analysis and interpretation of the data. Manzini G performed the meta-analysis. Manzini G and Kremer M wrote the manuscript. All authors gave their final approval of the version to be published.
Conflict-of-interest statement: The authors report no relevant conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Doris Henne-Bruns, MD, Professor, Department of General and Visceral Surgery, University Hospital of Ulm, Albert-Einstein-Allee 23, Ulm 89081, Germany. doris.henne-bruns@uniklinik-ulm.de
Received: March 22, 2019
Peer-review started: March 22, 2019
First decision: July 31, 2019
Revised: September 20, 2019
Accepted: October 14, 2019
Article in press: October 14, 2019
Published online: January 15, 2020
Abstract
BACKGROUND

In 2015, Kidane published a Cochrane review and meta-analysis to summarise the impact of preoperative chemotherapy versus surgery alone on survival for resectable thoracic esophageal cancer. The authors concluded that preoperative chemotherapy improved overall survival (OS).

AIM

The aim of this article was to assess the validity of the three most powerful studies included in the Cochrane review and the meta-analysis supporting the advantage of preoperative chemotherapy and to investigate the impact of an exclusion of these three studies on the result of the meta-analysis.

METHODS

OS was selected as the endpoint of interest. Among the ten included papers which analysed this endpoint, we identified the three publications with the highest weights influencing the final result. The validity of these papers was analysed using the CONSORT checklist for randomized controlled trials. We performed a new meta-analysis without the three studies to assess their impact on the general result of the original meta-analysis.

RESULTS

The three analysed studies revealed several inconsistencies. Inappropriate answers were found in up to one third of the items of the CONSORT checklist. Missing information about sample-size calculation and power, unclear or inadequate randomisation, and missing blinded set-up were the most common findings. When the three criticized studies were excluded in the meta-analysis, preoperative chemotherapy showed no benefit in OS.

CONCLUSION

The three most powerful publications in the Cochrane review show substantial deficits. After the exclusion of these studies from the meta-analysis, preoperative chemotherapy does not seem to result in an advantage in survival. We suggest a more critical appraisal regarding the validity of single studies.

Keywords: Esophageal cancer, Assessment of validity, Meta-analysis, CONSORT, Overall survival

Core tip: The quality of single studies is crucial in order to perform valid meta-analyses that are often used as basis for guideline recommendations. We critically analysed a recent Cochrane meta-analysis that supports the use of preoperative chemotherapy for resectable thoracic esophageal cancer in order to improve overall survival. The most powerful included studies showed several inconsistencies according to the requirements of the Consort checklist for randomized controlled trials. After the exclusion of these studies from the meta-analysis, preoperative chemotherapy does not seem to result in an advantage in survival. We suggest a more critical appraisal regarding the validity of single studies.