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Residual Disease Threshold After Primary Surgical Treatment for Advanced Epithelial Ovarian Cancer, Part 1: A Systematic Review and Network Meta-Analysis

Lookup NU author(s): Andrew Bryant, Eugenie Johnson, Dr Michael Grayling, Shaun HiuORCiD, Dr Ahmed Elattar, Professor Dawn CraigORCiD, Professor Luke ValeORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. BACKGROUND: We present a systematic review and network meta-analysis (NMA) that is the precursor underpinning the Bayesian analyses that adjust for publication bias, presented in the same edition in AJT. The review assesses optimal cytoreduction for women undergoing primary advanced epithelial ovarian cancer (EOC) surgery. AREAS OF UNCERTAINTY: To assess the impact of residual disease (RD) after primary debulking surgery in women with advanced EOC. This review explores the impact of leaving varying levels of primary debulking surgery. DATA SOURCES: We conducted a systematic review and random-effects NMA for overall survival (OS) to incorporate direct and indirect estimates of RD thresholds, including concurrent comparative, retrospective studies of ≥100 adult women (18+ years) with surgically staged advanced EOC (FIGO stage III/IV) who had confirmed histological diagnoses of ovarian cancer. Pairwise meta-analyses of all directly compared RD thresholds was previously performed before conducting this NMA, and the statistical heterogeneity of studies within each comparison was evaluated using recommended methods. THERAPEUTIC ADVANCES: Twenty-five studies (n = 20,927) were included. Analyses demonstrated the prognostic importance of complete cytoreduction to no macroscopic residual disease (NMRD), with a hazard ratio for OS of 2.0 (95% confidence interval, 1.8-2.2) for <1 cm RD threshold versus NMRD. NMRD was associated with prolonged survival across all RD thresholds. Leaving NMRD was predicted to provide longest survival (probability of being best = 99%). The results were robust to sensitivity analysis including only those studies that adjusted for extent of disease at primary surgery (hazard ratio 2.3, 95% confidence interval, 1.9-2.6). The overall certainty of evidence was moderate and statistical adjustment of effect estimates in included studies minimized bias. CONCLUSIONS: The results confirm a strong association between complete cytoreduction to NMRD and improved OS. The NMA approach forms part of the methods guidance underpinning policy making in many jurisdictions. Our analyses present an extension to the previous work in this area.

Publication metadata

Author(s): Bryant A, Johnson E, Grayling M, Hiu S, Elattar A, Gajjar K, Craig D, Vale L, Naik R

Publication type: Article

Publication status: Published

Journal: American Journal of Therapeutics

Year: 2023

Volume: 30

Issue: 1

Pages: e36-e55

Print publication date: 01/01/2023

Acceptance date: 02/04/2018

Date deposited: 18/01/2023

ISSN (print): 1075-2765

ISSN (electronic): 1536-3686

Publisher: Lippincott Williams & Wilkins


DOI: 10.1097/MJT.0000000000001584

PubMed id: 36608071


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Funder referenceFunder name
NIHR Applied Research Collaboration for North East and North Cumbria