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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.