Abstract
BACKGROUND: Vulval cancer is a rare gynaecological cancer. There is no standard approach for treating locally advanced primary vulval cancer (FIGO stage III and IV). Combined treatment modalities have been developed using radiotherapy, chemotherapy and surgery. The advantages and disadvantages of such treatment is not well evaluated. OBJECTIVES: To evaluate the effectiveness and safety of neoadjuvant and primary chemoradiation for women with locally advanced primary vulval cancer compared to other primary modalities of treatment such as primary surgery or primary radiation. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE (to July 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) or non-randomised studies that included multivariate analyses of chemoradiation in women with locally advanced, primary squamous cell carcinoma of the vulva. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. An adjusted hazard ratio (HR) for overall survival was calculated for one non-randomised study and risk ratios (RRs) were used in an RCT to compare five-year death rates and adverse events in women who received neoadjuvant, primary chemoradiation or primary surgery. Adverse events were also reported more extensively in a further non-randomised study. All results were displayed in single study analyses. MAIN RESULTS: One RCT and two non-randomised studies that allowed for multivariate analyses met the inclusion criteria and included a total of 141 women.One RCT found that neoadjuvant chemoradiation did not appear to offer longer survival compared to primary surgery in advanced vulval tumours (RR = 1.29, 95% confidence interval (CI) 0.87 to 1.91). There was also no statistically significant difference in survival between primary chemoradiation and primary surgery in a study that included 63 women (pooled adjusted HR= 1.09, 95% CI 0.37 to 3.17) and in another study that only included 12 eligible women and compared the same interventions (HR was non-informative when statistical adjustment was made).Adverse events were extensively reported in only one study, which found no statistically significant difference in risk of adverse events between primary chemoradiation and primary surgery due to the very small numbers in each group. In the RCT there was no observed statistically significant difference between neoadjuvant chemoradiation and primary surgery. Adverse events were not reported in the largest study of 63 women. Quality of life (QoL) was not reported in any of the included studies. All studies were at high risk of bias. AUTHORS' CONCLUSIONS: Women with advanced vulval tumours showed no significant difference in overall survival or treatment-related adverse events when chemoradiation (primary or neoadjuvant) was compared with primary surgery.The retrospective studies had a high risk of bias as the entry criteria for primary chemoradiation was based on inoperability or tumour requiring exenteration.The radiochemotherapy regimens varied widely. There was no data on QoL.There is no standard terminology for 'operable and inoperable vulval cancer', and for 'primary and neoadjuvant chemoradiation'. Stratification according to unresectability of the primary tumour and/or lymph nodes is needed, for good quality comparison.