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
Processing time: 160 Days and 1.3 Hours
ARTICLE HIGHLIGHTS
Research background

The use of chemotherapy (CTx) after curative surgery for non-metastatic rectal cancer and its role in improving patient survival remains controversial.

Research motivation

In 2012, Petersen et al[3] reported in a Cochrane review the effect of postoperative adjuvant CTx following curatively resected rectal cancer (Tany, Nany, M0) on overall survival. The authors identified 21 randomized controlled trials (RCT) reporting overall survival as primary endpoint. The meta-analysis of these RCTs showed a significant reduction in the risk of death (17%) among patients undergoing postoperative CTx as compared to those undergoing observation (hazard ratio = 0.83; 95% confidence interval: 0.76-0.91).

Research objectives

We aimed to analyze the quality of the data supporting the advantage of adjuvant CTx after surgery for rectal cancer.

Research methods

Using the CONSORT Checklist, the current analysis evaluated the validity of the three most powerful studies reviewed and analyzed within the Cochrane review by Petersen et al[3] 2012 which support the survival benefit of adjuvant CTx.

Research results

The detailed analysis of the three most powerful studies highlighted inconsistencies including inappropriate answers in up to 47% of the items of the CONSORT checklist. Inadequate or unclear randomization without allocation concealment, missing blinded set-up, absence of intention-to-treat analysis and omission of sample size calculation were the most common findings.

Research conclusions

We suggest a more critical appraisal regarding the validity of single RCTs, as these studies are included in meta-analysis that are the basis for guidelines.

Research perspectives

As CTx has several side effects for the patient and generates costs for the health system, it should be used only if its benefit is real.