Neoadjuvant chemotherapy before surgery versus surgery followed by chemotherapy for initial treatment in advanced epithelial ovarian cancer.

rationaleEpithelial ovarian cancer (EOC) presents at an advanced stage in the majority of women. These women require a combination of surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery. This is an update of a review first published in 2007 and last updated in 2025.

objectivesTo assess the advantages and disadvantages of treating women with advanced EOC with chemotherapy before cytoreductive surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows cytoreductive surgery (primary cytoreductive surgery (PCRS)). SEARCH

methodsWe searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 9 October 2025. We also checked the reference lists of relevant papers for further studies. We contacted the principal investigators of relevant studies for further information. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) of women with advanced EOC (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery. OUTCOMES: We extracted data on overall survival and progression-free survival, adverse events, surgically related mortality and morbidity, and quality-of-life outcomes. RISK OF BIAS: We used the Cochrane Risk of Bias 1 tool (RoB 1) to assess risk of bias in RCTs. SYNTHESIS

methodsWe conducted meta-analyses using random-effects models (due to heterogeneity between studies) to calculate hazard ratios (HR), risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) for all outcomes. We assessed the certainty of evidence according to the GRADE approach. INCLUDED STUDIES: A total of seven RCTs of varying quality and size met the inclusion criteria, with two new completed studies in this update. The studies assessed a total of 2650 women with stage III/IV ovarian cancer randomised to NACT followed by interval cytoreductive surgery (ICRS) or PCRS followed by chemotherapy. We included data from five studies in the meta-analyses (2380 participants). SYNTHESIS OF

resultsSurvival We found little or no difference between groups in overall survival (HR 1.00, 95% CI 0.91 to 1.10; I² = 2%; 5 studies, 2380 participants; high-certainty evidence) and likely little or no difference between groups in progression-free survival (HR 1.03, 95% CI 0.92 to 1.15; I² = 34%; 5 studies, 2380 participants; moderate-certainty evidence). Adverse events Adverse events, surgical morbidity, and quality-of-life outcomes were variably and incompletely reported across studies. NACT reduces postoperative mortality (0.5% in the NACT group versus 2.6% in the PCRS group) (RR 0.25, 95% CI 0.10 to 0.63; I² = 0%; 5 studies, 2201 participants; high-certainty evidence). There are probably clinically meaningful differences in favour of NACT compared to PCRS in overall surgically related adverse effects (grade 3+ (G3+)) (6.4% in the NACT group versus 29.4% in the PCRS group) (RR 0.34, 95% CI 0.14 to 0.82; I² = 82%; 3 studies, 1094 participants; moderate-certainty evidence). Organ resection NACT probably results in a large reduction in the need for stoma formation (6.9% in the NACT group versus 20.1% in the PCRS group) (RR 0.34, 95% CI 0.20 to 0.57; I² = 54%; 3 studies, 1291 participants; moderate-certainty evidence) and probably reduces the risk of needing bowel resection at the time of surgery (18.9% in the NACT group versus 38.6% in the PCRS group) (RR 0.49, 95% CI 0.35 to 0.69; I² = 79%; 5 studies, 2237 participants; moderate-certainty evidence). Quality of life Global quality of life on the EORTC QLQ-C30 produced imprecise results in three studies, with high levels of heterogeneity (quality of life at 6 months: MD 6.62, 95% CI -2.89 to 16.13; I² = 92%; 3 studies, 559 participants; very low-certainty evidence) and any differences might not be clinically meaningful. AUTHORS'

conclusionsThe available high- to moderate-certainty evidence shows there is likely little or no difference in primary survival outcomes between PCRS and NACT for those with advanced EOC who are suitable for either treatment option. NACT reduces the risk of postoperative mortality, and probably reduces the risk of serious adverse events around the time of surgery, and the need for stoma formation. These data are consistent across ~20 years of studies, through significant changes in surgical radicality, and should inform women and clinicians (involving specialist gynaecological multidisciplinary teams) to allow treatment to be tailored to the individual patient, taking into account surgical resectability, age, histology, stage, and performance status. Further data from studies unpublished in peer-reviewed journals and ongoing studies are awaited, but are unlikely to significantly change the results of this review.

fundingThis Cochrane review update had no dedicated funding. REGISTRATION: Protocol (2005): DOI: 10.1002/14651858.CD005343 Original review (2007): DOI: 10.1002/14651858.CD005343.pub2 Review update (2012): DOI: 10.1002/14651858.CD005343.pub3 Review update (2019): DOI: 10.1002/14651858.CD005343.pub4 Review update (2021): DOI: 10.1002/14651858.CD005343.pub5 Review updated (2021a): DOI: 10.1002/14651858.CD005343.pub6 Review updated (2025): DOI: 10.1002/14651858.CD005343.pub7.