Efficacy and safety of neoadjuvant chemotherapy versus primary debulking surgery in patients with ovarian cancer: a meta-analysis

Xiaofeng Lv; Shihong Cui; Xiao'an Zhang; Chenchen Ren

doi:10.3802/jgo.2020.31.e12

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Lv, Cui, Zhang, and Ren: Efficacy and safety of neoadjuvant chemotherapy versus primary debulking surgery in patients with ovarian cancer: a meta-analysis

Original Article

J Gynecol Oncol 2020;31(2):e12.

Published online: 4 March 2020

DOI: https://doi.org/10.3802/jgo.2020.31.e12

Efficacy and safety of neoadjuvant chemotherapy versus primary debulking surgery in patients with ovarian cancer: a meta-analysis

Xiaofeng Lv¹, Shihong Cui^1,, Xiao'an Zhang², Chenchen Ren¹

¹Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

²Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

Correspondence to Shihong Cui Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Front Street, Erqi District,Zhengzhou, Henan 450052, China. E-mail: superlxf1992@outlook.com

Received 20 February 2019 Revised 5 August 2019 Accepted 16 August 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Neoadjuvant chemotherapy (NACT) for the treatment of epithelial ovarian cancer (EOC) has remained controversial. This meta-analysis was performed to systematically assess the efficacy and safety of NACT versus primary debulking surgery (PDS) in patients with EOC.

Methods

PubMed, Embase, ClinicalTrials.gov, and Cochrane Library were queried to assess the therapeutic value of NACT versus PDS in EOC. Electronic databases were queried by using the keywords “ovarian cancer/neoplasms”, “primary debulking surgery”, and “neoadjuvant chemotherapy”.

Results

The available trials were pooled, and hazard ratios (HRs), relative risk ratios (RRs) and associated 95% confidence intervals (95% CIs) were determined. Sixteen trials involving 57,450 participants with EOC (NACT, 9,475; PDS, 47,975) were evaluated. We found that NACT resulted in markedly decreased overall survival than PDS in patients with EOC (HR=1.30; 95% CI=1.13–1.49; heterogeneity: p<0.001, I²=82.7%). Furthermore, our results demonstrated that the NACT group displayed increased completeness of debulking removal (RR=1.69, 95% CI=1.32–2.17; heterogeneity: p<0.001, I²=81.9%), and reduced risk of postsurgical death (RR=0.18, 95% CI=0.06–0.51; heterogeneity: p=0.698, I²=0%) and major infection (RR=0.29, 95% CI=0.17–0.51; heterogeneity: p=0.777, I²=0%) compared with patients administered PDS.

Conclusions

This meta-analysis indicated that NACT results in increased completeness of debulking removal, and reduced risk of postsurgical death and major infection compared with PDS, while PDS is associated with improved survival in comparison with NACT in EOC patients.

Keywords: Neoadjuvant Therapy, Debulking Surgical Procedure, Epithelial Ovarian Cancer, Meta-Analysis

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Fig. 1.

Flow diagram of study inclusion.

Fig. 3.

Post-operative complications and mortality. (A) Postsurgical death, (B) Major infections, and (C) Wound complications. CI, confidence interval; NACT, neoadjuvant chemotherapy; PDS, primary debulking surgery; RR, risk ratio.

Fig. 2.

Forest plots for survival and extent of surgical debulking. (A) OS, (B) PFS, (C) Completeness of debulking removal, and (D) Residual disease ≤1 cm. CI, confidence interval; HR, hazard ratio; NACT, neoadjuvant chemotherapy; PDS, primary debulking surgery; RR, risk ratio.

Table 1.

Characteristics of the studies included in this meta-analysis

First authors/ year of publication	Country	Mean age (yr)	Study design	No. of patients in intervention		Stage	Period of study (yr)	Outcomes assessed
First authors/ year of publication	Country	Mean age (yr)	Study design	NACT	PDS	Stage	Period of study (yr)	Outcomes assessed
Loizzi/2005 [18]	Italy	NACT: 64±11.35 PDS: 58±10.57	A case-control study	30	30	IIIC, IV	1994–2003	OS, PFS, and residual disease ≤1 cm
Vergote/2010 [7]	Belgium	NACT: 63±12 PDS: 62±15.25	RCT	334	336	IIIC, IV	1998–2006	OS, PFS, completeness of debulking removal, residual disease ≤1 cm, postsurgical death, and major infection
Milam/2011 [19]	USA	NACT: 61±13.5 PDS: 57±17	Cohort study	46	217	IIIC, IV	1993–2005	OS, PFS
Glasgow/2012 [20]	USA	NACT: 76.9±4.75 PDS: 75.9±4.75	Cohort study	42	62	IIIC, IV	1996–2009	OS, PFS, completeness of debulking removal, residual disease ≤1 cm, postsurgical death, major infection, and wound complication
Zheng/2012 [21]	China	NACT: 55.8 PDS: 54.5	Cohort study	30	37	IIIC, IV	2006–2009	OS, PFS
Taskin/2013 [31]	Turkey	NACT: 60.5±11.3 PDS: 56.4±12.6	Cohort study	74	23	IIIC, IV	2001–2010	OS
Worley/2013 [22]	USA	NACT: 74±3.5 PDS: 75±6.25	Cohort study	40	125	IIIC, IV	2000–2010	OS, PFS, postsurgical death, major infection, and wound complication
Colombo/2014 [23]	France	NA	Cohort study	147	220	IIIC, IV	1995–2010	OS
Fagö-Olsen/2014 [24]	Denmark	NACT: 66±3.25 PDS: 65±4.25	Cohort study	515	990	IIIC, IV	2005–2011	OS, completeness of debulking removal, and residual disease ≤1 cm
Kehoe/2015 [8]	UK	NACT: 65±13.5 PDS: 66±15.25	RCT	274	276	III, IV	2004–2010	OS, PFS, completeness of debulking removal, residual disease ≤1 cm, postsurgical death, and major infection
Bian/2016 [25]	China	NACT: 53±10.25 PDS: 50.7±15.75	Cohort study	114	225	IIIC, IV	2005–2010	OS, PFS, completeness of debulking removal, and residual disease ≤1 cm
Kessous/2016 [26]	Canada	NACT: 64.8±12.5 PDS: 58±11.5	Cohort study	127	136	IIIC	2003–2015	OS, PFS
Lim/2017 [27]	Korea	NACT: 57 PDS: 53	Cohort study	136	143	III, IV	2000–2009	OS, PFS
May/2017 [28]	USA	NACT: 62.2±12.25 PDS: 59.3±11	Cohort study	161	142	IIIC, IV	2004–2011	OS, completeness of debulking removal, and residual disease ≤1 cm
Seagle/2017 [29]	USA	NACT: 65±4 PDS: 61±4.5	Cohort study	7,348	44,970	III, IV	1998–2011	OS
Siesto/2018 [30]	Italy	NACT: 63.2±10.1 PDS: 60.8±10.7	Cohort study	50	50	IIIC, IV	2009–	OS, PFS, completeness of debulking removal, residual disease ≤1 cm, major infection, and wound complication

NACT, neoadjuvant chemotherapy; OS, overall survival; PDS, primary debulking surgery; PFS, progression-free survival; RCT, randomized controlled trial.

Table 2.

Methodological quality of observational studies included in the meta-analysis^*

First author/ year of publication	Representativeness of the exposed cohort	Selection of the unexposed cohort	Ascertainment of exposure	Outcome of interest not present at start of study	Control for important factor or additional factor	Outcome assessment	Follow-up long enough for outcomes to occur	Adequacy of follow-up of cohorts	Total quality scores
Loizzi/2005 [18]	☆	☆	☆	☆	☆	☆	☆	☆	8
Milam/2011 [19]	☆	☆	☆	–	☆	☆	☆	☆	7
Glasgow/2012 [20]	☆	☆	☆	☆	☆	☆	☆	☆	8
Zheng/2012 [21]	☆	☆	☆	☆	☆	☆	–	☆	7
Taskin/2013 [31]	☆	☆	☆	☆	☆	☆	☆	☆	8
Worley/2013 [22]	☆	☆	☆	☆	☆	☆	☆	☆	8
Fagö-Olsen/2014 [24]	☆	☆	☆	☆	☆	☆	☆	☆	8
Colombo/2014 [23]	☆	☆	☆	☆	☆	☆	–	☆	7
Bian/2016 [25]	☆	☆	☆	☆	☆	☆	☆	☆	8
Kessous/2016 [26]	☆	☆	☆	☆	☆	☆	☆	☆	8
May/2017 [28]	☆	☆	☆	☆	☆	☆	☆	☆	8
Lim/2017 [27]	☆	☆	☆	☆	☆	☆	☆	☆	8
Seagle/2017 [29]	☆	☆	☆	☆	☆	☆	☆	☆	8
Siesto/2018 [30]	☆	☆	☆	☆	☆	☆	–	☆	7

^* A study could be awarded a maximum of one star for each item except for the item control for important factor or additional factor.

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