B10Mixed meta-analysis of treatment options for locally advanced oesophageal squamous-cell carcinoma

Background: Different multimodality approaches including chemotherapy (CT) or chemo-radiotherapy (CRT) prior to surgery have been investigated for locally advanced oesophageal squamous cell cancer (OESCC), but direct comparisons are lacking. We performed a systematic review and mixed meta-analysis to assess the best strategy. Methods: Pubmed, EMBASE and abstracts presented at ASCO meetings, ASCO Gastrointestinal Cancers Symposium and ESMO congresses were searched for randomised controlled trials. Primary endpoint was overall survival. A mixed meta analysis of the network obtained was performed in a Bayesian framework using hazard ratios (HRs) and standard errors extracted from the publications. Risk of bias was addressed as suggested by the Cochrane Collaboration. Node-split models were built to assess inconsistency. Results: 25 trials including a total of 3866 patients were included. Most studies compared surgery with neoadjuvant CRT (n= 942) or CT (n = 997); 2 trials compared surgery with adjuvant CT (n= 447); 1 trial compared adjuvant with neoadjuvant CT (n = 330); 2 trials investigated definitive CRT vs. surgery (n = 81) or neoadjuvant CRT (n = 172); 3 studies compared surgery with either neoadjuvant RT, CT and CRT (n = 186), neoadjuvant CT and CRT (n = 473) or neoadjuvant CRT and adjuvant CRT (n = 238). Despite marked differences in study procedures, we found no evidence of significant heterogeneity or inconsistency: 10 studies were deemed at high risk of bias, 6 at low risk and 8 at unclear risk. Our results suggest that neoadjuvant CRT provides the most consistent survival advantage among the different multimodality treatment options (Table 1). Definitive and adjuvant CRT may represent effective alternatives to surgical resection, but the small number of studies prevents definitive conclusions. Neoadjuvant CT is associated to a lesser benefit. Conclusions: our analysis confirms that neoadjuvant CRT seems to be the best strategy in locally advanced OSCC, with definitive and adjuvant CRT as a reasonable alternative in selected cases.