Comparison of short-term outcomes of combined neoadjuvant chemotherapy and immunotherapy, neoadjuvant radiotherapy, and neoadjuvant chemotherapy for resectable locally advanced esophageal squamous cell carcinoma

Hai Zhang¹Zicheng Dai¹Bei Wang¹Bomeng Wu¹Jiangbo Lin²Wanli Lin^1*

• ¹Afiliated Gaozhou People's Hospital, Guangdong Medical University, Guangdong, China
• ²Fujian Medical University Union Hospital, Fuzhou, China

Background This study aimed to evaluate the safety and efficacy of neoadjuvant immunochemotherapy (nICT) compared to those of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced resectable ESCC undergoing neoadjuvant therapy followed by minimally invasive McKeown esophagectomy (MIE) between January 1, 2019, and January 1, 2022, were categorized into the nCT, nCRT, and nICT groups. Inverse probability of treatment weighting (IPTW) was used to balance the 13 baseline covariates across the groups. Post-IPTW comparisons included adverse events, surgical outcomes, pathologic complete response (PCR), tumor downstaging, and perioperative complications. Results A total of 437 patients were enrolled (nICT=218, nCRT=78, nCT=141). After propensity score matching(PSM), 78 patients were included in each group. During neoadjuvant therapy, the incidence of leukopenia was significantly higher in the nCRT (33.33%) and nICT (23.08%) groups than in the nCT (10.26%), p <0.05. Neutropenia rates followed a similar trend (nCRT: 19.23%; nICT: 17.95%; nCT: 2.56%, p <0.05). Immune-related dermatitis occurred in 10.26% of patients with nICT. Operative duration was significantly longer with nCRT (347.8 ± 80.8 min) than nCT (325.1 ± 52.6 min; p<0.05). The tumor-downstaging efficacy was ranked as follows: nICT > nCRT > nCT (p <0.05). Lymph node dissection:Yields: nCRT (26±11) < nICT (36±14) and nCT (35±12) (p<0.05),Stations: nICT (13±4) > nCRT (9±2) and nCT (11±2) (p<0.05). The PCR rates were 34.61% (nCRT), 26.92% (nICT), and 5.13% (nCT), respectively (p <0.05). Postoperative 30-day mortality occurred in three nCRT and one nCT patients. Postoperative arrhythmia incidence was highest with nICT (12.82%), intermediate with nCT (5.13%), and absent with nCRT (0.00%).Conclusion For locally advanced resectable ESCC, nCRT requires vigilant management because of its association with grade 3 treatment-related adverse events (AEs). While nICT demonstrates a lower incidence of severe (grade ≥3) non-immune toxicities compared to nCRT, supporting its controllable safety . nCRT achieved superior PCR rates versus nICT/nCT, but nICT showed greater nodal (N) downstaging efficacy. Conversely, nCRT provided enhanced primary tumor (T) control.