Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer.
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.


OBJECTIVE
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.


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).


METHODS
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.


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


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.


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.
Department of Obstetrics and Gynaecology, Musgrove Park Hospital, Taunton, UK. jo.morrison@obs-gyn.ox.ac.uk
Jo
J
Morrison
Krishnayan
K
Haldar
Sean
S
Kehoe
Theresa A
TA
Lawrie
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011183:Postoperative Complications; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents