title: Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer.
abstract: BACKGROUND
  Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of 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 subgroups of women 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 subgroups 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
  We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH).
  
  
  METHODS
  We selected randomised 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. We performed random-effects meta-analyses and subgroup analyses.
  
  
  RESULTS
  Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four trials were included in the meta-analyses and we considered them to be at a low risk of bias. Meta-analysis of five-year data from three trials indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (1008 women; hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.53 to 0.93). Likewise, meta-analysis of five-year data from four trials indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (1170 women; 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. In addition, these findings were robust over time (10-year PFS: two trials, 925 women; HR 0.67; 95% CI 0.54 to 0.84).Subgroup 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; two trials, 234 women) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85; two trials, 772 women). 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/medium risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these subgroup findings could be due to chance and should be interpreted with caution.
  
  
  CONCLUSIONS
  Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease. Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where optimal staging is not normally performed/achieved. In such settings, adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade 1 serous and endometrioid carcinoma and offered to all others with early stage disease.
authors.affiliation: Department ofObstetrics and Gynaecology, Salford Royal NHS Foundation Trust, Stott Lane,Salford, UK. brett.winter-roach@srft.nhs.uk. brett.winter_roach@btinternet.com.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Winter-Roach
authors.forename: Henry C
authors.initials: HC
authors.lastname: Kitchener
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Lawrie
mesh_terms: 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; D055088:Early Detection of Cancer; 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
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin; D008558:Melphalan