Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis

Abstract

Background: The benefit of neoadjuvant chemoradiotherapy in oesophageal cancer has been extensively studied but data on survival are still equivocal. Objective: To assess the effectiveness of chemoradiotherapy followed by surgery in the reduction of mortality in patients with resectable oesophageal cancer. Methods: Computerised bibliographic searches of MEDLINE and CANCERLIT (1970-2002) were supplemented with hand searches of reference lists. Study selection: Studies were included if they were randomised controlled trials (RCTs) comparing preoperative chemoradiotherapy plus surgery with surgery alone, and if they included patients with resectable histologically proven oesophageal cancer without metastatic disease. Six eligible RCTs were identified and included in the meta-analysis. Data extraction: Data on study populations, interventions, and outcomes were extracted from each RCT according to the intention to treat method by three independent observers and combined using the DerSimonian and Laird method. Results: Chemoradiotherapy plus surgery compared with surgery alone significantly reduced the three year mortality rate (odds ratio (OR) 0.53 (95% confidence interval (CI) 0.31-0.93); p = 0.03) (number needed to treat = 10). Pathological examination showed that preoperative chemoradiotherapy downstaged the tumour (that is, less advanced stage at pathological examination at the time of surgery) compared with surgery alone (OR 0.43 (95% CI 0.26-0.72); p = 0.001). The risk for postoperative mortality was higher in the chemoradiotherapy plus surgery group (OR 2.10 (95% CI 1.18-3.73); p = 0.01). Conclusions: In patients with resectable oesophageal cancer, chemoradiotherapy plus surgery significantly reduces three year mortality compared with surgery alone. However, postoperative mortality was significantly increased by neoadjuvant chemoradiotherapy. Further large scale multicentre RCTs may prove useful to substantiate the benefit on overall survival.

International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus

“…One further study showed a nonsignificant trend in favor of neoadjuvant RCT. Several previous meta-analyses [49][50][51][52] confirmed these results for adenocarcinoma. The metaanalysis by Gebski demonstrated a statistically significant survival benefit for both neoadjuvant chemotherapy and neoadjuvant RCT [40].…”

“…In esophageal cancer, a more detailed analysis of postoperative mortality of preoperative RCT showed increased mortality after RCT and resection only for patients with squamous cell carcinoma [62,63], whereas studies that predominantly included patients with adenocarcinoma had no increase or reduction in mortality [46][47][48]55]. In contrast, the metaanalysis by Fiorica showed that RCT in patients with adenocarcinoma increased post-operative mortality (HR 2.88, 95% CI 0.53-15) [49]. However, this was only observed in a study conducted in 1996 that used a form of radiotherapy that is now obsolete and also had other limitations [45].…”

Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study

“…However, surprisingly few phase III studies have been reported in which preoperative chemoradiotherapy followed by surgery was compared with surgery alone. Meta-analyses of these trials showed a small, if any, effect on survival (Kaklamanos et al, 2003;Urschel and Vasan, 2003;Fiorica et al, 2004). In addition, the results of a recently reported study were disappointing, showing no survival benefit for those patients treated with preoperative chemoradiotherapy (Burmeister et al, 2005).…”

“…Unfortunately, the impact of preoperative chemoradiotherapy with 5-FU and cisplatin on survival is uncertain. An improved 3-year survival was shown in three meta-analyses of randomised controlled trials comparing neoadjuvant chemoradiotherapy and surgery to surgery alone (Kaklamanos et al, 2003;Urschel and Vasan, 2003;Fiorica et al, 2004), but if the study by Walsh et al (1996) is excluded, this benefit is lost. Furthermore, chemoradiotherapy with 5-FU and cisplatin can induce severe toxicity and most patients have to be hospitalised for this treatment.…”

Radical Esophagectomy After Neoadjuvant Chemoradiation: Single Institutional Experience from Tertiary Cancer Centre in India

“…In the Fig. 1 Comparison of OS and DFS in group A and B meta-analysis by Florica et al [13], increase in survival was offset by double postoperative mortality while Urshel and Vasant [14] suggested an increase in mortality, with benefit of preoperative therapy seen only after 3 years of treatment. In a study by Bossetet al [15] there was improvement in disease free survival with induction therapy in stage I and II, but low overall survival due to increase in postoperative mortality from 3.6 to 12.3 %.…”