title: Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer.
abstract: BACKGROUND
  A previous systematic review found that giving neoadjuvant chemotherapy before surgery improved survival compared with radiotherapy. However, the role of neoadjuvant chemotherapy followed by surgery versus surgery alone is still unclear.
  
  
  OBJECTIVE
  To assess the role of neoadjuvant chemotherapy in women with early or locally-advanced cervical cancer.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) (to Issue 8, 2012), MEDLINE (OVID) (to Aug 2012), LILACS (to Aug 2012), Physician's Data Query (PDQ) (to Aug 2012). We sought both published and unpublished trials and undertook systematic searches of a number of trial sources with no restrictions.
  
  
  METHODS
  Randomised trials comparing neoadjuvant chemotherapy with surgery in women with early or locally-advanced cervical cancer who had not undergone any prior treatment likely to interfere with the treatment comparison. Trials giving radical radiotherapy for inoperable tumours and/or post-operative radiotherapy were also eligible. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), local and distant recurrence, rates of resection and surgical morbidity.
  
  
  METHODS
  Two authors independently extracted and checked data from trial reports, Depending on the type of outcome, trial hazard ratios (HRs) and odds ratios (ORs) were obtained or estimated from trial reports, or sought from trial investigators.
  
  
  RESULTS
  Six trials (1078 women) were identified for inclusion in this updated review. All six trials provided data on OS (1071 women) and PFS (1027 women). Data on resection rates and pathological response were only available for five trials (908 to 940 women) and data on recurrence were only available for four trials (737 women). Both OS (HR 0.77, 95% confidence interval (CI) 0.62 to 0.96, P = 0.02) and PFS (HR 0.75, 95% CI 0.61 to 0.93, P = 0.008) were significantly improved with neoadjuvant chemotherapy. The estimate for local recurrence was in favour of neoadjuvant chemotherapy (OR 0.67, 95% CI 0.45 to 0.99, P = 0.04), although heterogeneity was observed. The result was no longer significant when the random-effects model was used (OR 0.60, 95% CI 0.32 to 1.12, P = 0.11). Whilst not significant, estimates for distant recurrence (OR 0.72, 95% CI 0.45 to 1.14, P = 0.16) and rates of resection (OR 1.55, 95% CI 0.96 to 2.50, P = 0.07) tended to favour neoadjuvant chemotherapy, although heterogeneity was observed. Exploratory analyses of pathological response showed a significant decrease in adverse pathological findings with neoadjuvant chemotherapy (OR 0.54, 95% CI 0.40 to 0.73, P = < 0.0001 for lymph node status; OR 0.58, 95% CI 0.41 to 0.82, P = 0.002 for parametrial infiltration) which, despite substantial heterogeneity, was still significant when the random-effects model was used. There were also no differences in the effect of neoadjuvant chemotherapy on survival according to total cisplatin dose, chemotherapy cycle length or by cervical cancer stage.
  
  
  CONCLUSIONS
  Both OS and PFS were improved with neoadjuvant chemotherapy. Although the effects were less clear on all other pre-specified outcomes, they all tended to be in favour of neoadjuvant chemotherapy. Whilst these results appear to indicate that neoadjuvant chemotherapy may offer a benefit over surgery alone for women with early-stage or locally-advanced cervical cancer, the evidence is based on only a small number of trials, and further research may be warranted.
authors.affiliation: Meta-analysis Group, MRC Clinical Trials Unit, London, UK.lhr@ctu.mrc.ac.uk.
authors.forename: Larysa
authors.initials: L
authors.lastname: Rydzewska
authors.forename: Jayne
authors.initials: J
authors.lastname: Tierney
authors.forename: Claire L
authors.initials: CL
authors.lastname: Vale
authors.forename: Paul R
authors.initials: PR
authors.lastname: Symonds
mesh_terms: D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*