Key messages
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There is little difference in how long women with advanced epithelial ovarian cancer (EOC) survive, whether they have chemotherapy or surgery first. There is probably little difference in how long it takes for EOC to return after treatment.
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Giving chemotherapy prior to surgery (neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICRS)) probably reduces some of the risks of surgery; probably halves the risk of needing the bowel removed during surgery; and probably results in a large reduction in the risk of needing a stoma (bowel diverted through the abdominal wall into a bag to collect bowel contents).
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NACT/ICRS is an alternative to surgery followed by chemotherapy (primary cytoreductive surgery (PCRS) and adjuvant chemotherapy) in women with stage IIIC/IV EOC. Decisions about which treatment to have first will depend on patient preference, how well the woman is at time of diagnosis, the risks of surgery, and the amount and spread of disease.
What is epithelial ovarian cancer, and how is it treated?
Ovarian cancer is the eighth most common cancer worldwide in females. Around 90% of ovarian cancers are epithelial ovarian cancer (EOC), arising from the surface of the ovary or lining of fallopian tubes. Most women with EOC are diagnosed when their cancer is at a late stage, and their disease has spread throughout the abdominal cavity (stage IIIC/IV). Abnormal cells can spread throughout the abdominal cavity even when the primary tumour is microscopic (cannot be seen), attach to other surfaces, and grow over time before they cause symptoms. Although survival rates have improved over the last 20 years, only two in every five women with EOC are alive five years after diagnosis.
Treatment for ovarian cancer involves a combination of surgery and chemotherapy. Surgery aims to remove as much visible (macroscopic) cancer as possible. However, with widespread disease, surgery alone is unlikely to cure EOC, and most women will also need chemotherapy, which uses platinum-based medications to treat cells that cannot be removed by surgery (macroscopic disease) or cannot be seen (microscopic disease).
Traditionally, chemotherapy was given after surgery (primary cytoreductive surgery (PCRS) and adjuvant chemotherapy). However, chemotherapy can be used before surgery (neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICRS)). Women who receive NACT and ICRS complete the remaining cycles of chemotherapy following surgery.
Why is this important?
Women with advanced EOC may be very unwell at diagnosis or may have disease that would require extensive surgery to remove all visible disease, or both. NACT can help to shrink EOC prior to surgery, which might result in women needing less extensive surgery, or being made well enough to undergo surgery.
What did we want to find out?
We wanted to find out if giving chemotherapy before surgery was better than doing surgery first.
What did we do?
We reviewed the evidence on whether NACT and ICRS or PCRS followed by chemotherapy is more effective and safe in women diagnosed with advanced EOC. We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We included five studies involving a total of 1774 women. We were able to pool data from four studies (1692 women). These studies compared women who were given NACT/ICRS with women who underwent PCRS prior to chemotherapy.
We found little or no difference between treatments in time to death, and probably little or no difference in time to disease regrowth.
NACT/ICRS reduces deaths due to surgery and probably reduces the risk of some severe unwanted effects of surgery. NACT/ICRS probably results in a large reduction in the risk of needing a stoma (bowel diverted through the abdominal wall into a bag to collect bowel contents) and probably reduces the risk of needing the bowel removed during surgery (bowel resection). Overall, patient symptoms and quality of life may be slightly better at 6 months after treatment with NACT/ICRS, but this did not differ at 12 months after starting treatment. These differences might not be noticeable to patients.
The studies only enrolled women with advanced ovarian cancer (stage IIIC/IV), and many had extensive disease. We await the results of four ongoing studies and one unpublished full publication of a study.
What are the limitations of the evidence?
We are confident that there is little difference in overall survival (the length of time after diagnosis that a person is still alive) and fewer deaths due to surgery with NACT/ICRS. We are only moderately confident in other results related to survival, unwanted effects, and need for surgery to remove sections of bowel and need for a stoma, because women knew which treatment they were getting. We have little confidence in the quality of life evidence because the studies were done in different types of women, and approaches to surgery have changed over time, although the results of more recent studies are similar.
How up-to-date is the evidence?
The evidence is current to 21 March 2024.
The 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 likely reduces the risk of serious adverse events, especially those around the time of surgery, and the need for stoma formation. These data should inform women and clinicians (involving specialist gynaecological multidisciplinary teams) and allow treatment to be tailored to the individual patient, taking into account surgical resectability, age, histology, stage, and performance status. Data from an unpublished study and ongoing studies are awaited.
Epithelial ovarian cancer 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.
To 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)).
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 21 March 2024. We also checked the reference lists of relevant papers for further studies. We contacted the principal investigators of relevant trials for further information.
Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (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.
Two review authors independently extracted data and assessed risk of bias in each included trial. We extracted data of overall (OS) and progression-free survival (PFS), adverse events, surgically-related mortality and morbidity and quality of life outcomes. We used GRADE methods to determine the certainty of evidence.
We identified 2227 titles and abstracts through our searches, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1774 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the four studies where data were available and found little or no difference with regard to overall survival (OS) (Hazard Ratio (HR) 0.96, 95% CI 0.86 to 1.08; participants = 1692; studies = 4; high-certainty evidence) or progression-free survival in four trials where we were able to pool data (Hazard Ratio 0.98, 95% CI 0.88 to 1.08; participants = 1692; studies = 4; moderate-certainty evidence).
Adverse events, surgical morbidity and quality of life (QoL) outcomes were variably and incompletely reported across studies. There are probably clinically meaningful differences in favour of NACT compared to PDS with regard to overall postoperative serious adverse effects (SAE grade 3+): 6% in NACT group, versus 29% in PDS group, (risk ratio (RR) 0.22, 95% CI 0.13 to 0.38; participants = 435; studies = 2; heterogeneity index (I2) = 0%; moderate-certainty evidence). NACT probably results in a large reduction in the need for stoma formation: 5.9% in NACT group, versus 20.4% in PDS group, (RR 0.29, 95% CI 0.12 to 0.74; participants = 632; studies = 2; I2 = 70%; moderate-certainty evidence), and probably reduces the risk of needing bowel resection at the time of surgery: 13.0% in NACT group versus 26.6% in PDS group (RR 0.49, 95% CI 0.30 to 0.79; participants = 1565; studies = 4; I2 = 79%; moderate-certainty evidence). NACT reduces postoperative mortality: 0.6% in NACT group, versus 3.6% in PDS group, (RR 0.16, 95% CI 0.06 to 0.46; participants = 1623; studies = 5; I2 = 0%; high-certainty evidence). QoL on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scale produced inconsistent and imprecise results in three studies (MD -0.29, 95% CI -2.77 to 2.20; participants = 524; studies = 3; I2 = 81%; very low-certainty evidence) but the evidence is very uncertain and should be interpreted with caution.
This Cochrane review update had no dedicated funding.
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