Skeletal muscle wasting during neoadjuvant therapy as a prognosticator in patients with esophageal and esophagogastric junction cancer: A systematic review and meta-analysis

Considerable controversies exist regarding the severity of skeletal muscle wasting (SMW) during neoadjuvant therapy (NAT) and its impact on therapeutic outcomes in patients with esophageal or esophagogastric junction cancer (EC/EGJC). This systematic review and meta-analysis aimed to resolve these issues. Particularly, the prognostic value of SMW during NAT was compared to pre-NAT and pre-surgery sarcopenia status.We searched PubMed, Embase, and Cochrane Library databases through October 13th, 2021 to identify cohort studies focusing on SMW during NAT and therapeutic outcomes in EC/EGJC patients. Both neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy were studied. A meta-analysis was conducted to quantify SMW and increased sarcopenia during NAT. Therapeutic outcomes include perioperative morbidities and survival profiles. A separate meta-analysis investigating the impacts of pre-NAT/pre-surgery sarcopenia on therapeutic outcomes was synchronously performed.Twenty-five studies with 2706 participants were included in this review. The pooled SMW during NAT were -2.47 cm2/m2 in skeletal muscle index and -0.23 cm2/m2 in psoas muscle index, with wasting proportion reaching 4.44%. The pooled prevalence rate of sarcopenia increased from 53.1% before NAT to 65.8% before surgery. Neoadjuvant chemoradiotherapy, advanced age, and being male were identified as risk factors for severe SMW during NAT. Notably, severe SMW during NAT showed a greater hazard ratio (HR) than pre-NAT and pre-surgery sarcopenia in predicting overall survival (HR 1.92, P < 0.001; HR 1.17, P = 0.036; and HR 1.28, P = 0.011, respectively) and recurrence-free survival (HR 1.51, P = 0.002; HR 1.27, P = 0.008; and HR 1.38, P = 0.006, respectively). However, severe SMW during NAT was not significantly associated with perioperative morbidities.SMW during NAT is a novel prognosticator that is different from sarcopenia for poor survival in EC/EGJC patients. Interventions aiming at maintaining skeletal muscle during NAT are anticipated to promote therapeutic outcomes.