Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer

  • Review
  • Intervention

Authors


Abstract

Background

Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment is to perform surgery first and then give chemotherapy. However, it is not yet clear whether there are any advantages to using chemotherapy before surgery.

Objectives

To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before cytoreductive surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows maximal cytoreductive surgery.

Search methods

For the original review we searched, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2006), MEDLINE (Silver Platter, from 1966 to 1 Sept 2006), EMBASE via Ovid (from 1980 to 1 Sept 2006), CANCERLIT (from 1966 to 1 Sept 2006), PDQ (search for open and closed trials) and MetaRegister (most current search Sept 2006). For this update randomised controlled trials (RCTs) were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2011) and the Cochrane Gynaecological Cancer Specialised Register (2011), MEDLINE (August week 1, 2011), EMBASE (to week 31, 2011), PDQ (search for open and closed trials) and MetaRegister (August 2011).

Selection criteria

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

Data were extracted by two review authors independently, and the quality of included trials was assessed by two review authors independently.

Main results

One high-quality RCT met the inclusion criteria. This multicentre trial randomised 718 women with stage IIIc/IV ovarian cancer to NACT followed by interval debulking surgery (IDS) or primary debulking surgery (PDS) followed by chemotherapy. There were no significant differences between the study groups with regard to overall survival (OS) (670 women; HR 0.98; 95% CI 0.82 to 1.18) or progression-free survival (PFS) (670 women; HR 1.01; 95% CI 0.86 to 1.17).

Significant differences occurred between the NACT and PDS groups with regard to some surgically related serious adverse effects (SAE grade 3/4) including haemorrhage (12 in NACT group vs 23 in PDS group; RR 0.50; 95% CI 0.25 to 0.99), venous thromboembolism (none in NACT group vs eight in PDS group; RR 0.06; 95% CI 0 to 0.98) and infection (five in NACT group vs 25 in PDS group; RR 0.19; 95% CI 0.07 to 0.50). Quality of life (QoL) was reported to be similar for the NACT and PDS groups.

Three ongoing RCTs were also identified.

Authors' conclusions

We consider the use of NACT in women with stage IIIc/IV ovarian cancer to be a reasonable alternative to PDS, particularly in bulky disease. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account resectability, age, histology, stage and performance status. These results cannot be generalised to women with stage IIIa and IIIb ovarian cancer; in these women, PDS is the standard. We await the results of three ongoing trials, which may change these conclusions.

Plain language summary

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

Epithelial ovarian cancer is the seventh most common cancer worldwide in women under the age of 65 years, 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 symptoms are vague, often occur only after the cancer has spread, and can be misdiagnosed as being caused by other benign conditions. In Europe, just over a third of women diagnosed with ovarian cancer are alive five years after diagnosis.

Conventional treatment for ovarian cancer is to have surgery (laparotomy) to remove the womb, ovaries, the omentum (a fatty structure (apron) that hangs down from the stomach and drapes over the intestines in the upper abdomen) and to sample the lymph nodes (glands) in the pelvis and abdomen. The intention of surgery is to stage the disease (assess where the cancer has spread to) and remove as much of the cancer as possible (debulking or cytoreduction). However, since most women will have widespread disease, surgery alone does not cure the disease and further treatment is necessary, in the form of chemotherapy. Chemotherapy for ovarian cancer uses platinum-based drugs (carboplatin and cisplatin) to treat any cancer cells that cannot be removed by surgery or are too small to be seen (microscopic disease).

Chemotherapy can be used before surgery (also called neoadjuvant chemotherapy) with the aim of shrinking the cancer and making it easier to remove all of the cancer.

One good-quality study in women with advanced ovarian cancer was included in this review. This study compared 336 women who were given chemotherapy first with 334 women who underwent surgery first and found no difference between the two treatments with respect to the time to death or the time to progression of the disease, that is chemotherapy before surgery had a similar effect on survival as the conventional treatment. The study only enrolled women with stage IIIc/IV ovarian cancer. (Stage IIIc is when the tumour that has spread into the abdomen is greater than 2 cm in size.) A large proportion of women in the study had very bulky tumours. We therefore assessed the evidence to be of moderate quality and concluded that neoadjuvant chemotherapy is a reasonable alternative to primary surgery in women with bulky stage IIIc/IV disease. Three other studies are currently being conducted that will hopefully contribute more evidence to guide clinical practice in this area in the future.

Ancillary