Surgery to remove tumour so that it is not visible with the naked eye prolongs survival in women with recurrent epithelial ovarian cancer

Epithelial ovarian cancer is a disease in which malignant cells form in the tissue covering the ovary. It accounts for about 90% of ovarian cancers; the remaining 10% arise from germ cells or the sex cords and stroma of the ovary. Women with epithelial ovarian cancer that has returned after primary treatment (recurrent disease) may need secondary surgery to remove all or part of the cancer. When ovarian cancer recurs after more than six months it is considered suitable for further treatment with platinum chemotherapy (platinum sensitive).

The results of this review suggest that surgery may be associated with improved outcomes in terms of prolonging life in some women (platinum-sensitive disease). In particular, surgery removing all visible disease is associated with a significant improvement in survival, although this may be due to the cancer biology facilitating surgery, rather than the surgery itself. We conclude from the current evidence that surgery with the aim of removing all visible disease should be considered in women with recurrent ovarian cancer on an individual basis. However, the data are limited to non-randomised studies with a median age of women in their 50s and early 60s, which may not be representative of all women with ovarian cancer. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

Authors' conclusions: 

In women with platinum-sensitive recurrent ovarian cancer, ability to achieve surgery with complete cytoreduction (no visible residual disease) is associated with significant improvement in overall survival. However, in the absence of RCT evidence, it is not clear whether this is solely due to surgical effect or due to tumour biology. Indirect evidence would support surgery to achieve complete cytoreduction in selected women. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

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Background: 

The standard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy. Most women with primary ovarian cancer achieve remission on this combination therapy. For women achieving clinical remission after completion of initial treatment, most (60%) with advanced epithelial ovarian cancer will ultimately develop recurrent disease. However, the standard treatment of women with recurrent ovarian cancer remains poorly defined. Surgery for recurrent ovarian cancer has been suggested to be associated with increased overall survival.

Objectives: 

To evaluate the effectiveness and safety of optimal secondary cytoreductive surgery for women with recurrent epithelial ovarian cancer. To assess the impact of various residual tumour sizes, over a range between 0 cm and 2 cm, on overall survival.

Search strategy: 

We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to December 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For databases other than MEDLINE, the search strategy has been adapted accordingly.

Selection criteria: 

Retrospective data on residual disease, or data from randomised controlled trials (RCTs) or prospective/retrospective observational studies that included a multivariate analysis of 50 or more adult women with recurrent epithelial ovarian cancer, who underwent secondary cytoreductive surgery with adjuvant chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm.

Data collection and analysis: 

Two review authors (KG, TA) independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis.

Main results: 

There were no RCTs; however, we found nine non-randomised studies that reported on 1194 women with comparison of residual disease after secondary cytoreduction using a multivariate analysis that met our inclusion criteria. These retrospective and prospective studies assessed survival after secondary cytoreductive surgery in women with recurrent epithelial ovarian cancer.

Meta- and single-study analyses show the prognostic importance of complete cytoreduction to microscopic disease, since overall survival was significantly prolonged in these groups of women (most studies showed a large statistically significant greater risk of death in all residual disease groups compared to microscopic disease).

Recurrence-free survival was not reported in any of the studies. All of the studies included at least 50 women and used statistical adjustment for important prognostic factors. One study compared sub-optimal (> 1 cm) versus optimal (< 1 cm) cytoreduction and demonstrated benefit to achieving cytoreduction to less than 1 cm, if microscopic disease could not be achieved (hazard ratio (HR) 3.51, 95% CI 1.84 to 6.70). Similarly, one study found that women whose tumour had been cytoreduced to less than 0.5 cm had less risk of death compared to those with residual disease greater than 0.5 cm after surgery (HR not reported; P value < 0.001).

There is high risk of bias due to the non-randomised nature of these studies, where, despite statistical adjustment for important prognostic factors, selection is based on retrospective achievability of cytoreduction, not an intention to treat, and so a degree of bias is inevitable.

Adverse events, quality of life and cost-effectiveness were not reported in any of the studies.

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