Systematic Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Jun 30, 2019; 7(6): 309-322
Published online Jun 30, 2019. doi: 10.13105/wjma.v7.i6.309
Surgery with adjuvant or neoadjuvant treatment vs surgery alone for resectable pancreatic cancer: A network meta-analysis
Pu Shen, Kai-Jun Huang, Chuan-Zhao Zhang, Li Xiao, Tao Zhang
Pu Shen, Li Xiao, Tao Zhang, Department of Anesthesia, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Kai-Jun Huang, Chuan-Zhao Zhang, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
Author contributions: Shen P and Zhang T designed and organized the study protocol; Huang KJ and Xiao L reviewed and selected the papers; Shen P and Zhang CZ extracted and analyzed the data and wrote the paper; all authors had access to the data and statistical analyses, approved the final article, and attested to the validity of the results.
Supported by the Medical Scientific Research Foundation of Guangdong Province, No. A2017229.
Conflict-of-interest statement: The authors disclose no potential conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Tao Zhang, MD, Doctor, Professor, Department of Anesthesia, the First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan II Road, Guangzhou 510080, Guangdong Province, China. zhangt45@mail2.sysu.edu.cn
Telephone: +86-20-37583761 Fax: +86-20-37583761
Received: April 13, 2019
Peer-review started: April 15, 2019
First decision: May 16, 2019
Revised: June 4, 2019
Accepted: June 10, 2019
Article in press: June 10, 2019
Published online: June 30, 2019
Abstract
BACKGROUND

Pancreatic cancer is one of the most common and lethal malignancies worldwide. The common treatment options for resectable pancreatic cancer include surgery alone, neoadjuvant chemotherapy (CT), neoadjuvant chemoradiotherapy (CRT), adjuvant CT, and adjuvant CRT. However, the optimal treatment is still controversial.

AIM

To identify the most effective approach for pancreatic cancer using network meta-analysis.

METHODS

Eligible studies were searched from PubMed, MEDLINE, EMBASE, Cochrane database, and Google scholar. We searched and included randomized controlled trials reporting on neoadjuvant and adjuvant therapies. For direct comparisons, standard pairwise meta-analysis was performed using the inverse variance DerSimonian-Laird random-effects model. For indirect comparisons, Bayesian network meta-analysis was used to combine direct and indirect evidence. We used relative hazard ratios (HRs) to estimate death difference of different treatments, and relative odds ratios (ORs) for toxic effects. Treatment effects were ranked based on their efficacy for improving survival or reducing toxicity using rankogram. The quality of evidence of estimates from direct comparison and network meta-analysis was evaluated following the GRADE approach.

RESULTS

We included 13 high quality trials with 1591 participants in this network meta-analysis. Compared with surgery alone [pooled HR = 0.7, 95% confidence interval (CI): 0.62-0.79] and surgery with adjuvant CRT (pooled HR = 0.6, 95%CI: 0.54-0.72), surgery with adjuvant CT had a higher rate of overall survival. In contrast, standard pairwise meta-analysis showed a statistically significant survival advantage of surgery with adjuvant CT compared with surgery alone (pooled HR = 0.75, 95%CI: 0.63-0.89; P < 0.001). Rankogram showed that surgery with adjuvant CT was most likely to rank the best in terms of overall survival (probability: 94.2%), followed by surgery alone (probability: 5.8%). No significant differences in overall toxicity or haematological toxicity were found between all the therapies. High quality evidence supported surgery with adjuvant CT over surgery alone for increasing overall survival. Moderate quality evidence supported surgery with adjuvant CT over surgery with adjuvant CRT for increasing overall survival.

CONCLUSION

Surgery with adjuvant CT prolongs overall survival compared with surgery alone and surgery with adjuvant CRT, suggesting surgery with adjuvant CT is the optimal treatment for resectable pancreatic cancer.

Keywords: Pancreatic cancer, Surgery, Network meta-analysis, Adjuvant therapy, Neoadjuvant therapy

Core tip: No consensus is available in previous studies about the most beneficial treatment option for resectable pancreatic cancer. This is the first network meta-analysis comparing the efficiency of surgery alone, neoadjuvant chemotherapy (CT), neoadjuvant chemoradiotherapy (CRT), adjuvant CT, and adjuvant CRT. We investigated these treatment options in terms of overall survival and toxicity. We found that surgery with adjuvant CT prolonged overall survival compared with surgery alone and surgery with adjuvant CRT. Surgery with adjuvant CT is the optimal treatment for resectable pancreatic cancer.