Evidence-Based Medicine
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2020; 12(4): 503-513
Published online Apr 15, 2020. doi: 10.4251/wjgo.v12.i4.503
Adjuvant chemotherapy in curatively resected rectal cancer: How valid are the data?
Giulia Manzini, Fabius Hapke, Ian N Hines, Doris Henne-Bruns, Michael Kremer
Giulia Manzini, Fabius Hapke, Doris Henne-Bruns, Michael Kremer, Department of General and Visceral Surgery, University of Ulm, Ulm 89081, Germany
Ian N Hines, Department of Nutrition Science, College of Allied Health Sciences, East Carolina University, Greenville, NC 27834, United States
Michael Kremer, Department of General and Visceral Surgery, Hospital of Aarau, Aarau 5000, Switzerland
Author contributions: Manzini G, Kremer M and Henne-Bruns D contributed substantially to the conception and design of the study; Manzini G and Hapke F contributed to the analysis and interpretation of the data; Manzini G performed the meta-analysis; Manzini G, Hines IN and Kremer M wrote the manuscript; all authors gave their final approval of the version to be published.
Conflict-of-interest statement: The authors declare that they have no competing interests
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Giulia Manzini, MD, MSc, Doctor, Surgeon, Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, Ulm 89081, Germany. giulia.manzini@uniklinik-ulm.de
Received: November 7, 2019
Peer-review started: November 7, 2019
First decision: December 5, 2019
Revised: February 27, 2020
Accepted: March 22, 2020
Article in press: March 22, 2020
Published online: April 15, 2020
Abstract
BACKGROUND

According to the result of the Cochrane review published in 2012, postoperative adjuvant chemotherapy (CTx) is associated with a survival benefit for rectal cancer patients operated for cure in comparison to patients who underwent only the surgical resection.

AIM

To analyze the quality of the data supporting the advantage of adjuvant CTx after surgery for rectal cancer. In the times of increasing health care costs, it is imperative to offer the patient an evidence-based therapy that justifies potential side effects as well as costs.

METHODS

Overall survival was selected as endpoint of interest. Among the 21 included papers which analyzed this endpoint, we identified those three publications which have the highest weights to influence the final result. The validity of these papers was analyzed using the CONSORT checklist for randomized controlled trials. We performed a second meta-analysis excluding the three analyzed studies (n = 18) in order to assess their impact on the overall result of the original meta-analysis. Finally, we performed a third meta-analysis excluding all studies (n = 16) which showed a statistically improved overall survival.

RESULTS

The detailed analysis of the three most relevant RCTs according to the items of the CONSORT checklist showed several pitfalls. In up to 47% of the items, inappropriate answers were found. Generally, a lack of information regarding the randomization procedure as well as the absence of allocation concealment, blinded set-up, of intention-to-treat analysis and omission of sample size calculation were common problems of the analyzed studies. The exclusion of these three studies from the meta-analysis did not affect the general result of the meta-analysis, still confirming a survival advantage after adjuvant chemotherapy. After exclusion of single studies with a statistically significant outcome improvement, the meta-analysis of the remaining 16 studies again shows a statistically significant result due in part to a large remaining sample size.

CONCLUSION

The three most powerful publications show substantial deficits. We suggest a more critical appraisal regarding the validity of single studies because a meta-analysis cannot overcome the limitations of individual trials by pooling treatment effect estimates to generate a single best estimate.

Keywords: Rectal cancer, Validity, Meta-analysis, CONSORT checklist, Postoperative chemotherapy, Overall survival

Core tip: The role of adjuvant chemotherapy (CTx) in curatively resected rectal cancer needs to be considered cautiously. Petersen et al published a Cochrane review in 2012 which found an improvement in survival in patients receiving adjuvant CTx after surgery in comparison to those who were treated by surgery only. The result was based on 21 studies, 5 of them supporting the advantage of CTx. Among these, we selected the three most powerful studies and assessed their validity, which was poor. Surprisingly, our meta-analysis without these studies yielded similar results as the original study (still in favor of adjuvant CTx).