Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer.
BACKGROUND
A prior 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), (Issue 2, 2009), MEDLINE (to March 2009), LILACS (to March 2009), Physician's Data Query (PDQ) (to March 2009). Both published and unpublished trials were sought and systematic searches of a number of trial sources were undertaken with no restrictions.


METHODS
Randomised controlled trials (RCTs) 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
Data were extracted from trial reports and independently checked by two review authors. 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 (1072 women) were identified for inclusion in the review. Although data on PFS was available for all six trials (1036 women), data on overall survival, resection rates and pathological response were only available for five trials (909 to 938 women) and data on recurrence were only available for three trials (604 women). Whilst PFS was significantly improved with neoadjuvant chemotherapy (HR = 0.76, 95% CI = 0.62 to 0.94, p = 0.01), no OS benefit was observed (HR = 0.85, 95% CI = 0.67 to 1.07, p = 0.17). Furthermore, estimates for both local (OR = 0.76, 95% CI = 0.49 to 1.17, p = 0.21) and distant (OR = 0.68, 95% CI = 0.41 to 1.13, p = 0.13) recurrence and rates of resection (OR = 1.55, 95% CI = 0.96 to 2.50, p = 0.07) only tended to be in favour of neoadjuvant chemotherapy, and heterogeneity was observed. Exploratory analyses of pathological response showed a significant decrease in adverse pathological findings with neoadjuvant chemotherapy (OR = 0.54, 95% CI = 0.39 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 a high level of heterogeneity was still significant when the random effects model was used. There was also no difference in the effect of neoadjuvant chemotherapy according to total cisplatin dose, chemotherapy cycle length or by cervical cancer stage.


CONCLUSIONS
Despite outcomes tending to be in favour of neoadjuvant chemotherapy few, including overall survival, were significant. Therefore, it remains unclear whether neoadjuvant chemotherapy consistently offers a benefit over surgery alone for women with early-stage or locally advanced cervical cancer.
Rydzewska
Larysa
L
Meta-analysis Group, MRC Clinical Trials Unit, 222 Euston Road, London, UK, NW1 2DA.
Tierney
Jayne
J
Vale
Claire L
CL
Symonds
Paul R
PR
D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*