Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer.
BACKGROUND
Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease. Ten to fifteen percent of all cases are diagnosed early when there is still a good possibility for cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum based chemotherapy but the precise role of this treatment in sub-groups of patients with differing prognoses needs to be defined.


OBJECTIVE
To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine; firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly; to determine if clinical sub-groups of differing prognosis based on histological sub-type or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery.


METHODS
An electronic search was performed using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008) and CancerLit. The search strategy was developed using free text and medical subject headings (MESH).


METHODS
The review authors selected those clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures.


METHODS
Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. Random effects meta-analyses and sub-group analyses were conducted.


RESULTS
Five randomised controlled trials (RCTs), enrolling 1277 women, with 46 to 110 months follow-up, met the inclusion criteria. These trials had low risk of bias. Meta-analysis of three trials with adequate data, assessing 1008 women, indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (hazard ratio (HR) 0.71; 95% CI 0.53 to 0.93). Likewise, meta-analysis of four trials with adequate data, assessing 1170 women, indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (HR 0.67; 95% CI 0.53 to 0.84). The trials included in these meta-analyses gave consistent estimates of the effects of chemotherapy.Sub-group analysis suggested that women who had optimal surgical staging of their disease were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85). One trial showed a benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these sub-group findings could be due to chance.


CONCLUSIONS
Adjuvant platinum based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early stage epithelial ovarian cancer. However, even given the limits of sub-group analyses, there is strong evidence that optimal surgical staging identifies patients who have either little or nothing to gain from adjuvant chemotherapy. Taken together with the lack of a survival advantage seen in patients with "low-risk" cancers in the ICON1 trial, it appears safe to withhold adjuvant chemotherapy from optimally staged patients with well differentiated tumours.
Winter-Roach
Brett A
BA
Department of Obstetrics and Gynaecology, Salford Royal NHS Foundation Trust, Stott Lane, Salford, UK, M6 8HD.
Kitchener
Henry C
HC
Dickinson
Heather O
HO
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008558:Melphalan / Q000627:therapeutic use; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin; D008558:Melphalan