ArticlesPrimary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial
Introduction
Ovarian cancer is the leading cause of death from gynaecological cancer in developed countries.1 More than 75% of women have advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stage IIIC or IV) at diagnosis, of whom a substantial proportion are unwell and unfit and have a 5-year survival rate of less than 25%.1 Primary cytoreductive surgery followed by platinum-based chemotherapy is the mainstay of treatment for advanced disease. Although no randomised trials of primary surgery exist, observational studies consistently report that a lower postoperative tumour residuum is associated with longer survival.2, 3, 4, 5, 6, 7, 8 Achievement of optimum debulking (defined in the study period as disease <1 cm in maximum diameter at completion of surgery) can need complex and widespread surgery, and is more likely to be achieved when done by specialist gynaecological oncologists.9, 10, 11 Even so, many women treated in specialist centres will have bulky residual tumour after surgery.
An alternative treatment strategy using primary chemotherapy with delayed surgery has been developed. This strategy is based on the high response rate to platinum-based chemotherapy and many women have had rapid symptomatic improvement and reduction in tumour burden with it. The primary-chemotherapy strategy seemed to increase optimum debulking rates and reduce surgery related complications in observational studies,12, 13 but two meta-analyses of non-randomised studies produced conflicting results on the effect of delaying surgery on survival.14, 15
We designed the CHORUS trial to test the hypothesis that giving primary chemotherapy with delayed surgery could result in survival similar to primary surgery, with reduced surgical morbidity. A non-inferiority design was chosen because we judged that a reduction in surgery related morbidity without detriment to survival would justify the use of this treatment strategy in clinical practice.
Section snippets
Study design and participants
We designed this trial as an investigator-designed and led multicentre, randomised phase 3 trial that took place in the UK and New Zealand (appendix). We obtained national ethical and regulatory approvals in both countries and local approvals at each centre. Trial conduct and progress were monitored by an independent data monitoring committee and overseen by the UK Medical Research Council Clinical Trials Unit (MRC CTU) Gynaecological Cancer Trial Steering Committee. All participating centres
Results
Between March 1, 2004, and Aug 30, 2010, 552 women were recruited: 539 from 74 UK trial centres and 13 from two centres in New Zealand. Surgery was done at 64 trial centres. Two women were randomly assigned in error and withdrawn from the trial immediately after; one woman because she was unable to give informed consent to participation and the other because of an administrative error. These women were excluded from all analyses, and 550 women were therefore included in the final analyses (
Discussion
Our study (CHORUS) showed that for women with stage III or IV ovarian cancer with a high tumour burden, survival after receiving primary chemotherapy followed by surgery was not inferior compared with receiving primary surgery, and surgical morbidity and mortality were significantly reduced (panel).
The median survival of 22–24 months was less than expected, but was similar in both groups. The explanation for the less-than-expected overall survival might be attributed to the older median age of
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