Esophageal cancer (EC) is a highly malignant digestive system cancer with significant incidence and mortality rates. Globally, there were ~604,000 new cases and 544,000 deaths from esophageal cancer annually. It ranks as the seventh most commonly diagnosed cancer and the sixth leading cause of cancer-related deaths worldwide (1). In China, according to the latest data from the National Cancer Center, esophageal cancer is the sixth most common cancer and the fifth leading cause of cancer deaths (2). In China, ESCC accounts for ~90% of esophageal cancer cases, with a particularly high burden in rural and central regions due to risk factors such as smoking, alcohol consumption and diets high in nitrosamines (3). Unfortunately, ESCC is often asymptomatic in early stages, with only 15–20% of patients diagnosed at localized stages. The majority present with advanced disease, characterized by dysphagia, weight loss or obstruction, by which time treatment options are limited and prognosis deteriorates significantly. Despite advances in treatment, its efficacy remains limited, with a 5-year survival rate of approximately 15–20% (4,5). This poor prognosis, coupled with its high prevalence, makes esophageal cancer a major threat to global and Chinese public health. In previous years, immunotherapy, particularly programmed cell death protein 1 (PD-1) inhibitors, has garnered notable attention and application in the treatment of various malignant tumors, with growing evidence supporting its role in neoadjuvant therapy for esophageal cancer. Concurrently, neoadjuvant therapy has emerged as a cornerstone for locally advanced ESCC, primarily aiming to downstage tumors, enhance resectability and mitigate postoperative recurrence (6,7). Camrelizumab, a domestically developed PD-1 inhibitor, offers advantages in accessibility and cost-effectiveness for Chinese patients. Prior studies, such as the NIC-ESCC2019 trial (a multicenter phase 2 study), demonstrated a 39.2% pathological complete remission (pCR) rate with camrelizumab plus chemotherapy (8,9), but real-world comparative data against chemotherapy alone remain limited.

To address this knowledge gap, a retrospective cohort study was performed to compare outcomes between neoadjuvant hemotherapy alone and camrelizumab-combined therapy in Chinese patients with ESCC. The present study analyzed clinical data from patients who underwent neoadjuvant therapy followed by radical esophagectomy, providing additional insights into the role of camrelizumab in ESCC treatment.

According to statistical data from the National Cancer Center, the incidence and mortality rates of esophageal cancer in China in 2020 were 13.8/100,000 and 12.7/100,000, ranking sixth and fourth among malignant tumors, respectively (10). ESCC accounts for ~90% of esophageal cancer cases in China (11). In previous years, the approach to treating esophageal cancer has evolved from simple surgical interventions to comprehensive surgical-based treatments, with neoadjuvant therapy emerging as a cornerstone in managing locally advanced resectable esophageal cancer. Neoadjuvant therapy refers to the administration of relevant treatment before surgery, aiming to reduce the tumor size and extent or downgrade the tumor stage, thereby enhancing surgical outcomes and reducing the risk of tumor recurrence and metastasis (12,13).

Since its initial report in the New England Journal of Medicine in 2012 (14), neoadjuvant concurrent chemoradiotherapy has been adopted as the global standard for managing locally advanced resectable esophageal/esophagogastric junction cancer. Moreover, research advancements from Yang et al (15) have revealed that neoadjuvant chemoradiotherapy confers substantial survival benefits in locally advanced resectable ESCC, offering more precise guidance for treating this condition in China (15). Despite the high incidence and poor prognosis of esophageal cancer, comprehensive treatment strategies such as neoadjuvant therapy result in improved patient outcomes and enhanced quality of life.

In previous years, immunotherapy has been widely adopted in tumor treatment, with PD-1 inhibitors marking a major breakthrough and emerging as a novel research avenue in esophageal cancer treatment (16,17). Camrelizumab, an independently developed PD-1 inhibitor in China, functions by obstructing the binding of PD-1 and programmed death-ligand 1 (PD-L1), thereby disrupting the PD-1/PD-L1 signaling pathway and inhibiting tumor cell proliferation. Its efficacy has been demonstrated across various malignant tumors, including Hodgkin's lymphoma, hepatocellular carcinoma, non-small cell lung cancer, ESCC and nasopharyngeal carcinoma (18–24). Research indicates that preoperative camrelizumab can enhance the R0 resection rate in patients with locally advanced esophageal cancer, and when combined with chemotherapy, can markedly prolong patient median survival time (25). In a multicenter trial investigating locally advanced resectable ESCC, the combination of two cycles of neoadjuvant chemotherapy with camrelizumab yielded a notable pCR rate of 39.2%, with a surgical R0 resection rate reaching 98% (26). Previous studies (27–29) have also reported satisfactory outcomes with neoadjuvant chemotherapy combined with camrelizumab in the treatment of locally advanced resectable ESCC, with a pCR rate >30% and an R0 resection rate >90%.

The enhanced pCR rates observed with camrelizumab in ESCC arise from synergistic immunomodulatory mechanisms (30). As a selective PD-1 inhibitor, camrelizumab disrupts PD-1/PD-L1 signaling through sustained receptor internalization, reversing T-cell exhaustion and amplifying cytotoxic CD8⁺ T-cell infiltration into tumor cores (31). This checkpoint blockade synergizes with chemotherapy-induced immunogenic priming: Paclitaxel/cisplatin promote tumor antigen release, upregulate PD-L1 expression via IFN-γ/STAT1 signaling and trigger immunogenic cell death to enhance dendritic cell activation (32). Concurrently, the regimen remodels the tumor microenvironment by suppressing immunosuppressive cancer-associated fibroblasts, normalizing aberrant vasculature and alleviating metabolic acidosis to restore T-cell functionality (33). The temporal coordination between chemotherapy-induced immunogenic ‘priming’ and camrelizumab-driven immune ‘amplification’ establishes a self-reinforcing antitumor cycle (34), collectively driving superior pCR outcomes.

In the present study, the observation group exhibited a significantly higher pCR rate compared with the control group (40.0 vs. 8.6%). Additionally, all patients in the observation group achieved complete resection (R0), whereas only 32 patients (91.4%) in the control group achieved R0 resection. No grade ≥4 AEs were observed in either group. AEs induced by chemotherapy drugs in both groups were mild and manageable and did not impede the treatment regimen. In the observation group, the incidence of RCCEP was 45.7% (16 out of 35), whereas no cases were observed in the control group. All RCCEP cases resolved within 1–2 months following treatment discontinuation, and none required extended interventions or alternative management strategies. Symptomatic management, including local skin care and appropriate anti-inflammatory measures, was administered to a few patients. Camrelizumab-related RCCEP is predominantly mild, reversible and occurs exclusively on the skin surface. This observation aligns with prior reports on RCCEP in camrelizumab-treated populations (35). This reaction may be attributed to the potential of camrelizumab to promote capillary proliferation in conjunction with vascular endothelial growth factor (36). Camrelizumab monotherapy may lead to such AEs, but its incidence can be markedly reduced by concurrent treatment with targeted anti-angiogenic drugs (37).

In summary, the combination of camrelizumab, paclitaxel and cisplatin as a neoadjuvant therapy for locally advanced esophageal cancer shows notable clinical efficacy and manageable safety. Compared with neoadjuvant chemotherapy alone, the combination therapy offered benefits in antitumor activity without increased AEs. However, several limitations must be acknowledged. First, the retrospective design introduces potential selection biases, particularly in patient inclusion criteria and treatment allocation, which may influence the representativeness of the cohort. Second, the relatively small sample size (n=70) reduces statistical power to detect subtle differences in outcomes and limits the generalizability of findings to broader populations. Furthermore, the limited follow-up duration in the present study precludes robust analysis of long-term survival outcomes (such as 5-year overall survival) and late-onset treatment-related toxicities. To address this, the follow-up is being actively expanded for this cohort through to 2028, with planned analyses of 5-year overall survival and recurrence-free survival. To address these limitations, future multicenter prospective studies with larger cohorts and extended follow-up periods are warranted to validate the findings.

In conclusion, neoadjuvant camrelizumab combined with paclitaxel and cisplatin may notably enhance pCR rates in locally advanced ESCC, with a manageable safety profile. These findings suggest potential clinical benefit, but confirmation through prospective, randomized trials is essential to validate the regimen's efficacy and long-term outcomes.