Neoadjuvant chemoradiotherapy (nCRT) followed by minimally invasive esophagectomy (MIE) has similar safety and better histopathologic outcomes than neoadjuvant chemotherapy (nCT) followed by MIE for patients with locally advanced esophageal squamous cell carcinoma (ESCC), investigators reported in JAMA Surgery.

This prospective, open-label, randomized clinical trial was conducted from January 1, 2017, to December 31, 2018, in 10 high-volume institutions in China. The primary outcome was 3-year overall survival. Secondary outcomes included postoperative complications, mortality, postoperative pathologic outcomes, recurrence-free survival time, and quality of life.

A total of 264 patients with locally advanced ESCC (226 men [85.6%]; mean [SD] age, 61.4 [6.8] years) were included and randomly allocated to either the nCRT group (n = 132) or the nCT group (n = 132). Before treatment was initiated, 3 patients withdrew consent (1 in the nCRT group and 2 in the nCT group), and thus 131 patients in nCRT group and 130 patients in nCT group received neoadjuvant treatment.

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The postoperative complications rate was 47.4% (54 of 114) in the nCRT group and 42.6% (46 of 108) in the nCT group, with no significant difference between the 2 groups (difference, 4.8%; 95% CI, −8.2 to 17.5; P =.48). The 90-day mortality rate was 3.5% (4 of 114) in the nCRT group and 2.8% (3 of 108) in the nCT group (P =.94).

The nCRT and nCT groups also had similar R0 resection rates (97.3% [109 of 112] vs 96.2% [100 of 104]; P =.92, respectively). Participants in the nCRT group had a better tumor regression grade compared with the nCT group (residual tumor, 0%: 40 of 112 [35.7%] vs 4 of 104 [3.8%]; P <.001, respectively), fewer lymph nodes involved (ypN0: 74 of 112 [66.1%] vs 48 of 104 [46.2%]; P =.03, respectively), and a better ypTNM stage (stage I: 58 of 112 [51.8%] vs 21 of 104 [20.2%]; P <.001, respectively).

Intention-to-treat analysis showed that the 1-year overall survival rate was 87.1% (115 of 132) in the nCRT group compared with 82.6% (109 of 132) in the nCT group (P =.30). Deaths resulting from tumor progression or recurrence occurred significantly less frequently in the nCRT group than in the nCT group (9 of 132 [6.8%] vs 19 of 132 [14.4%]; P =.046), although deaths from nontumor causes were similar (8 of 132 [6.1%] vs 4 of 132 [3.0%]; P =.24).

Among several limitations noted by the researchers, patients with poorer performance status and older patients were not included in the study cohort. Thus, applicability of this therapy to these patients requires additional research. Additionally, this study only included patients with ESCC, and so whether these results are applicable to those with esophageal or esophagogastric junction adenocarcinoma also requires further investigation.

“This clinical trial showed that nCRT followed by MIE could result in a better histopathologic outcome, as well as similar morbidity and mortality rates, compared with nCT,” the study authors concluded. “It is worth observing the long-term survival benefit of nCRT vs nCT in the follow-up.”


Wang H, Tang H, Fang Y, et al. Morbidity and mortality of patients who underwent minimally invasive esophagectomy after neoadjuvant chemoradiotherapy vs neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma a randomized clinical trial. JAMA Surg. Published online March 17, 2021. doi: 10.1001/jamasurg.2021.0133