Adding pembrolizumab to standard neoadjuvant chemoradiotherapy is not associated with increased postoperative...

The current standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) consists of neoadjuvant chemoradiotherapy (nCRT) followed by curative surgery. Recent single-arm trials have demonstrated that incorporating immune checkpoint inhibitors (ICIs) into neoadjuvant regimens improves pathological complete response (pCR) rates. However, the comparative risk of postoperative complications between nCRT and neoadjuvant chemoimmunoradiotherapy (nCIRT) followed by esophagectomy in patients with ESCC remains unclear.

We retrospectively analyzed ESCC patients who underwent neoadjuvant therapy followed by esophagectomy at Ruijin Hospital (April 2019-April 2025). Postoperative complications were defined as adverse events occurring within 90 days after surgery, primarily involving the respiratory, digestive, and cardiovascular systems. Severity was assessed using the Clavien-Dindo classification (CDC), and Grade IIIA or higher levels were considered severe complications. To overcome limitations of CDC in capturing the full morbidity spectrum and burden, we further evaluated complications using the Comprehensive Complication Index (CCI).

A total of 271 patients who underwent curative esophagectomy were enrolled, including 169 in the nCRT group and 102 in the nCIRT group. No significant differences were observed in age or gender distribution between the two groups. According to Clavien-Dindo classification, there was no significant difference in overall complication rates between the nCRT and nCIRT groups (p = 0.76). Regarding severe complications (Grade ≥ IIIA), the overall incidence was 35.50% in the nCRT group and 28.43% in the nCIRT group (p = 0.23). The CCI analysis indicated a comparable morbidity burden, with median CCI scores of 22.60 in both nCRT and nCIRT cohorts (p = 0.65). Furthermore, no statistically significant differences were observed in subgroups analyses of patients with cardiac complications, pulmonary complications, anastomotic leakage, chyle leakage and wound infections, especially in severe complications.

In this retrospective analysis of a prospectively maintained cohort, the addition of pembrolizumab to nCRT was not associated with a statistically significant increase in postoperative complications among patients with ESCC. These findings provided preliminary evidence regarding the perioperative safety of this combination. Further studies were warranted to investigate the long-term efficacy of nCIRT for the treatment of ESCC.