Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers

Background: The long-term survival benefits of neoadjuvant chemotherapy (NAC) and chemoradiotherapy (NACR) for oesophageal carcinoma are well established. Both are burdened, however, by toxicity that could contribute to perioperative morbidity and mortality. Methods: MEDLINE, the Cochrane Library and Embase were searched to capture the incidence of any postoperative complications, cardiac complications, respiratory complications, anastomotic leakage, postoperative 30-day mortality, total postoperative mortality and treatment-related mortality in randomized clinical trials comparing NAC or NACR with surgery alone, or NAC versus NACR. Meta-analyses comparing NAC and NACR were conducted by using adjusted indirect comparison. Results: Twenty-three relevant studies were identified. Comparing NAC or NACR with surgery alone, there was no increase in morbidity or mortality attributable to neoadjuvant therapy. Subgroup analysis of NACR for squamous cell carcinoma (SCC) suggested an increased risk of total postoperative mortality and treatment-related mortality compared with surgery alone: risk ratio 1.95 (95 per cent confidence interval 1.06 to 3.60 ; P = 0.032) and 1.97 (1.07 to 3.64; P = 0.030) respectively. A combination of direct comparison and adjusted indirect comparison showed no difference between NACR and NAC regarding morbidity or mortality. Conclusion: Neither NAC nor NACR for oesophageal carcinoma increases the risk of postoperative morbidity or perioperative mortality compared with surgery alone. There was no clear difference between NAC and NACR. Care should be taken with NACR in oesophageal SCC, where an increased risk of postoperative mortality and treatment-related mortality was apparent.