Does giving chemotherapy before surgery improve survival or quality of life for women with advanced ovarian epithelial cancer?

What is the issue?
Epithelial ovarian cancer, arising from the surface layer of the ovaries or lining of the fallopian tubes, is the ninth most common cancer worldwide in women, and is the most common form of ovarian cancer (approximately 90% of ovarian cancers). Unfortunately, most women with ovarian cancer present at a late stage, when their disease has spread throughout the abdomen. This is because ovarian cancer often arises from the ends of the fallopian tubes, from where single cells can drop out into the abdominal cavity even when the primary tumour is microscopic. These tumour cells circulate around the abdominal cavity in the lubricating peritoneal fluid, implant on other surfaces and grow over time until they cause symptoms. Even then, symptoms, such as bloating and bowel disturbance (most commonly constipation), are nonspecific and easily attributed to more common benign conditions. In Europe and the UK, just over a third of women diagnosed with ovarian cancer are alive five years after diagnosis.

Conventional treatment for ovarian cancer involves two modalities of treatment: surgery and chemotherapy. The intention of surgery is to stage the disease (assess where the cancer has spread to) and remove as much of the visible (macroscopic) cancer as possible (known as debulking or cytoreduction), preferably to the point where the surgical team is not able to see any visible residual disease in the abdominal cavity. However, since most women will have widespread disease, surgery alone is unlikely to cure the disease and most will also need chemotherapy. Chemotherapy for ovarian cancer uses platinum-based drugs to treat cells that cannot be removed by surgery (macroscopic disease) or are too small to be seen (microscopic disease). Traditionally, chemotherapy was given after surgery (primary debulking surgery (PDS) and adjuvant chemotherapy) . However, chemotherapy can be used before surgery (known as neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS)) with the aim of shrinking the cancer and allowing women to get better prior to undertaking major surgery. Women who receive NACT and IDS complete the remaining cycles of chemotherapy following surgery.

What did we do?
We searched electronic databases up to October 2020 and conducted handsearches for unpublished reports of trials. We included randomised controlled trials (RCTs) of NACT and IDS versus surgery (primary debulking surgery (PDS)) followed by chemotherapy in women diagnosed with advanced stage epithelial ovarian cancer and pooled study outcome data, where appropriate.

What did we find?
We identified 2227 titles and abstracts from the search. From these, we found five RCTs which met our inclusion criteria, including a total of 1774 women with advanced ovarian cancer. We were able to pool data from four studies. These trials compared women who were given chemotherapy prior to surgery (NACT) with women who underwent surgery first (PDS) prior to chemotherapy. We found little or no difference between the two treatments with respect to the time to death and probably little or no difference in the time to progression of the disease. We found that giving NACT reduces the risk of postoperative mortality and need for stoma formation, for which we have high certainty. NACT probably reduces the risk of some severe complications of surgery, but some of these data were less well reported in the included studies and so we have moderate to low certainty about these results. The studies only enrolled women with stage IIIc/IV ovarian cancer i.e. those who had advanced disease; a large proportion of women in this review had very bulky tumours. We are currently awaiting results of three ongoing studies and one unpublished full publication of a study that is awaiting classification that will hopefully contribute more evidence to guide clinical practice in this area in the future.

What does this mean?
Overall, the evidence was of moderate to high certainty. There is little or no difference in how long women with advanced epithelial ovarian cancer will survive, if they have chemotherapy or surgery first, where both treatments are planned. There is probably little or no difference in how long it will take for the cancer to regrow after initial treatment. NACT probably reduces some of the risks of surgery, probably halves the risk of needing the bowel removed, and probably has a large reduction in the risk of needing the bowel diverted through the abdominal wall via a stoma (a bag attached to the abdominal wall to collect bowel contents). NACT/IDS is an alternative to PDS followed by chemotherapy in women with bulky stage IIIc/IV disease. Individual decisions about which treatment to have first will depend on the individual woman's wishes, how well she is at the time of diagnosis, the risks of surgery and the burden and distribution of disease.

Authors' conclusions: 

The available high to moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT probably reduces the risk of serious adverse events, especially those around the time of surgery, and reduces the risk of postoperative mortality and the need for stoma formation. These data will inform women and clinicians (involving specialist gynaecological multidisciplinary teams) and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.

Read the full abstract...

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 whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before debulking surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows debulking surgery (primary debulking surgery (PDS)).

Search strategy: 

We searched the following databases up to 9 October 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information.

Selection criteria: 

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.

Data collection and analysis: 

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.

Main results: 

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.

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