Esophageal cancer (EC) represents a highly lethal malignancy with considerable global incidence and mortality, as evidenced by the 604,000 new cases and 544,000 deaths reported in 2020, positioning it as the seventh most prevalent and sixth most fatal cancer worldwide (1). EC is classified into two pathological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). In China, ESCC predominates, accounting for approximately 90% of esophageal cancer cases (2), whereas in Europe and America, 70–80% of esophageal cancers are adenocarcinomas (3). The prognosis for EC remains poor, with an 5-year overall survival (OS) rate of less than 30%, and post-surgical survival outcomes are similarly unsatisfactory (4, 5). Recently, neoadjuvant therapies, such as neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT), followed by surgical intervention, have emerged as the standard treatment approach for patients with locally advanced EC (6). High-quality clinical studies, including ESCORT-NEO, have demonstrated that the combination of neoadjuvant chemotherapy and immunotherapy (NCIT) is safe and efficacious for patients with locally advanced EC (7). We can discuss the case in a multidisciplinary commission with the nutritionist and the oncologist for neoadjuvant treatment (8). Following neoadjuvant therapy, numerous patients with EC exhibit tumor regression. However, surgical intervention becomes increasingly complex and hazardous due to edema, adhesion, and scar tissue formation within the esophageal bed. Additionally, some patients may experience adverse events related to the treatment, resulting in compromised physical health (9). Investigating surgical approaches that prioritize patient safety, efficacy, and long-term survival outcomes is imperative.

The progression of minimally invasive surgical techniques has facilitated a shift in EC surgery from the conventional open esophagectomy (OE) to minimally invasive esophagectomy (MIE) (10). MIE is a surgical approach for esophageal cancer that primarily utilizes video-assisted thoracoscopic esophagectomy (VATE). MIE includes procedures such as video-assisted thoracoscopic esophagectomy (VATE) and total minimally invasive esophagectomy (TMIE). Among these techniques, VATE is considered the foundational technology and cornerstone of MIE within the thoracic field, and it is extensively utilized in clinical practice. In this study, We concentrates on VATE, include hybrid esophagectomy procedures. The two main procedural classifications under this paradigm are the McKeown esophagectomy (three-field approach) and the Ivor-Lewis esophagectomy (two-field approach). Concurrently, the global adoption of robot-assisted minimally invasive esophagectomy (RAMIE) is rising (11). A retrospective study compared OE and VATE for EC. The findings indicated that VATE significantly reduced operation time and postoperative hospital stay, while also enhancing the 5-year OS rate of patients (12). A retrospective study compared RAMIE with OE, revealing that the former is associated with a reduced length of hospital stay and a lower reoperation rate. However, it also showed an increased incidence of postoperative pulmonary embolism, with no significant difference in long-term survival between the two methods (13). Additionally, clinical trials have compared RAMIE with VATE. These trials indicated that RAMIE may enhance lymph node dissection in patients with esophageal cancer. However, no significant differences were observed in mortality, complication rates, or perioperative outcomes between the two groups (14). While several studies have examined the advantages and disadvantages of various surgical techniques, there is a paucity of clinical research specifically addressing surgical methods for EC patients who have undergone neoadjuvant therapy, with existing studies often constrained by limited sample sizes. Consequently, it is imperative to perform a network meta-analysis utilizing all available data to comprehensively investigate the safety, efficacy, and long-term survival outcomes associated with different surgical approaches-namely, OE, VATE, and RAMIE-in the context of locally advanced EC following neoadjuvant therapy.

The combination of neoadjuvant therapy with surgical resection has now become the standard treatment modality for locally advanced EC. Over decades of continuous refinement and innovation, radical esophagectomy has undergone a remarkable transformation, evolving from conventional open procedures to minimally invasive approached. In recent years, robot-assisted surgery has become more and more popular, which reduces the trauma of patients and raises the requirements for surgeons. The neoadjuvant therapy-induced cytotoxic effects on the tumor may enhance the fragility of both the neoplastic and adjacent tissues, thereby elevating the susceptibility to rupture or hemorrhage during surgical intervention, this may augment the complexity and associated risks of the surgical procedure (25). In addition, neoadjuvant chemoradiotherapy may induce immunosuppression, which could compromise the body’s self-repair capacity by impairing the immune system’s critical role in tissue regeneration 27). Importantly, Immune checkpoint inhibitors (ICIs) have the potential to induce adverse effects, including cardiotoxicity, hepatotoxicity, and thyroid dysfunction, which are linked to endocrine disruptions. These complications may adversely affect postoperative recovery in patients with EC and elevate the risk of perioperative morbidity (26). The optimal surgical strategy for patients undergoing neoadjuvant therapy continues to be a topic of considerable discussion within the medical community. A systematic literature review indicates that contemporary clinical studies and meta-analyses have largely concentrated on pairwise comparisons. For example, a meta-analysis by Zhang et al. (27) thoroughly assessed the efficacy differences between RAMIE and VATE in the context of thoracic surgery. Their findings revealed that RAMIE offers notable technical advantages over VATE in certain anatomical areas, such as mediastinal and left recurrent laryngeal nerve lymph node dissection. Furthermore, the group undergoing RAE demonstrated a favorable trend in 3-year OS.

Substantial evidence gaps persist in direct comparative studies of RAMIE, VATE, and OE for EC following neoadjuvant therapy. This situation introduces a risk of bias in clinical decision-making due to reliance on multiple indirect comparisons. The analysis aimed to elucidate comparative advantages and limitations in performing radical esophagectomy following neoadjuvant therapy. This study represents the inaugural application of network meta-analysis methodology to synthesize both direct and indirect evidence through the development of a Bayesian probability model. This approach overcomes the constraints of traditional pairwise comparisons, enabling the concurrent quantitative evaluation and ranking of the three surgical procedures. Consequently, it offers a more comprehensive evidence-based foundation for optimizing the selection of surgical strategies.

This network meta-analysis systematically evaluated data from 7 randomized or observational studies involving 1,847 patients with EC who underwent neoadjuvant therapy. The study assessed three surgical approaches-OE, RAMIE, and VATE-focusing on critical clinical outcomes, including postoperative complication rates, operative time, R0 resection rate, and 3-year OS.

The network meta-analysis demonstrated no statistically significant differences in operative time, R0 resection rate, lymph node yield, or overall complications among OE, RAMIE, and VATE. However, intervention rankings revealed clinically relevant gradients: OE exhibited superior probability for reducing operative time (OE > RAMIE > VATE) and optimizing lymphadenectomy (OE > RAMIE >VATE), while RAMIE ranked highest for complication minimization (RAMIE > OE > VATE).For 3-year OS, pairwise comparisons between OE and VATE showed equivalent survival outcomes (HR = 1.12, 95% CI = 0.87-1.44), with sensitivity analyses confirming robustness despite predominantly observational evidence. These results suggest that while statistical equivalence exists across surgical modalities, nuanced performance differences may guide procedure selection based on individualized clinical priorities.

Esophagectomy for EC is a complex surgical procedure characterized by a relatively high incidence of complications, encompassing esophageal dissection, lymphadenectomy, and esophagogastric anastomosis. Common postoperative complications include pulmonary infections, hoarseness resulting from recurrent laryngeal nerve injury, anastomotic leakage, and chylothorax (28). The advent and increasing utilization of RAMIE have demonstrated substantial benefits in mitigating postoperative complications. Notably, RAMIE showed significant decrease in cardiopulmonary complications. Compared to traditional OE, RAMIE has decreased incidence of postoperative pneumonia (29). OE may offer advantages in terms of operation time, because OE can be more direct and effective, particularly with complex tumors. With advancements in surgeon skill and procedural optimization, the operative time for both VATE and RAMIE has shortened significantly. While initial studies noted longer durations for RAMIE—attributed to the learning curve associated with 3D visualization, robotic instrumentation, and team integration—increasing surgical experience leads to greater efficiency (30). As surgeons and operating room teams climb the learning curve, streamlined workflows and improved intraoperative management allow RAMIE to achieve operative times comparable to, or even shorter than, those of conventional minimally invasive esophagectomy (31). Furthermore, RAMIE demonstrates superior outcomes in recurrent laryngeal nerve preservation, a critical factor for reducing postoperative voice and swallowing dysfunction, thereby significantly enhancing patients’ quality of life (32). Nevertheless, OE is associated with greater invasiveness and is linked to increased intraoperative blood loss, postoperative complications, and postoperative pain when compared to RAMIE or VATE (33).

The network meta-analysis of included studies revealed no statistically significant differences in R0 resection rates among the three surgical approaches. Although cumulative ranking probabilities indicated RAMIE had the highest likelihood of achieving R0 resection (SUCRA = 47.3%), the minimal disparity compared with OE (SUCRA = 43.8%) and wide confidence intervals collectively suggest clinical equipoise across these techniques. This finding underscores that while technical variations exist in operative details and postoperative recovery profiles, comparable oncological efficacy in R0 resection can be attained with RAMIE, OE, and VATE under specific clinical contexts. These results provide clinicians with greater flexibility in procedure selection, supported by existing evidence demonstrating therapeutic equivalence in tumor eradication outcomes among surgical modalities. A meta-analysis encompassing several studies revealed no statistically significant difference between RAMIE and OE concerning the critical prognostic indicator of the R0 resection rate (34). A prospective cohort study conducted by Tokyo Medical University, encompassing more than ten years of postoperative follow-up, established clinical equivalence in R0 resection rates and long-term survival outcomes between the RAMIE and VATE groups. Additionally, the study highlighted the superior efficacy of RAMIE in minimizing procedure-related complications and intraoperative blood loss (35). Given the high risk associated with esophagectomy, it is may better to centralize patients in high-volume hospitals (36).

The quantity of excised lymph nodes serves as a crucial parameter in assessing surgical efficacy in treating EC. This study demonstrated no statistically significant differences in the total number of dissected lymph nodes among the OE, VATE, and RAMIE groups (P > 0.05). However, network meta-analysis revealed that OE exhibited superior performance in cumulative ranking of lymph node dissection quantity (SUCRA = 59.5%), demonstrating significantly higher values compared to both RAMIE (SUCRA = 21.3%) and VATE (SUCRA = 19.2%). The three surgical approaches (OE, RAMIE, and VATE) demonstrate distinct characteristics and advantages in lymph node dissection. Compared to minimally invasive approaches, open esophagectomy (OE) offers an inherent advantage for lymph node dissection due to its larger operative space and more straightforward manual access. In contrast, VATE, as a minimally invasive approach, offers clinical advantages including reduced operative trauma and expedited postoperative recovery. The study by Li Zhenhua et al. (37) demonstrated comparable lymph node yield between VATE and OE, highlighting the technically demanding nature of VATE requiring advanced surgical proficiency. Notably, the procedure’s inherent limitations of two-dimensional visualization may potentially compromise dissection completeness in anatomically complex cases, particularly when operating surgeons lack sufficient thoracoscopic expertise. In recent years, RAMIE has attracted increasing attention in EC surgery. The robotic system’s wristed instruments, like the EndoWrist in the da Vinci platform, offer multiple degrees of freedom, surpassing human hand dexterity in tight surgical spaces. Tremor filtration removes hand tremors, boosting the surgeon’s ability to work in complex areas. These features enhance the precision and flexibility of robotic-assisted surgery., In addition, the RAMIE offers greater comfort to the first operator that should not be underestimated (38). Lei J et al. (39) showed although RAMIE has no significant superiority in total lymph node yield, but stratified analyses of nodal stations in existing clinical investigations have identified enhanced dissection efficacy in anatomically critical zones, particularly the left recurrent laryngeal nerve basin and mediastinal regions where conventional approaches encounter technical constraints. A meta-analysis comparing the short-term outcomes between RAMIE and conventional minimally invasive esophagectomy found that RAMIE offers advantages in lymph node dissection, particularly yielding a higher number of retrieved lymph nodes in the left recurrent laryngeal nerve area (40). Furthermore, the first Irish study on robotic esophagectomy also demonstrated that robotic surgery achieved a greater lymph node harvest compared to other surgical approaches (41). Therefore, we conclude that with the growing proficiency of surgeons in robotic techniques, RAMIE demonstrates a superior ability for lymph node dissection compared to OE or VATE, particularly in challenging areas such as the left recurrent laryngeal nerve region.

Long-term survival continues to be the primary endpoint in oncological research. The current study demonstrated similar 3-year OS rates between the OE and VATE cohorts, with 64.5% and 67.2% rates. The analysis revealed no statistically significant difference in survival outcomes (P > 0.05). These results indicate that with ongoing advancements in thoracoscopic surgical techniques, VATE has achieved long-term oncological outcomes comparable to the traditional open approach, underscoring its clinical non-inferiority in the comprehensive management of cancer. This observation has been consistently confirmed by multiple high-quality studies in recent years. Specifically, findings from the Japanese 10-year clinical trial JCOG1409, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated comparable 3-year OS rates between the VATE and OE groups (82.0%, 70.9%, respectively; P > 0.05). These data indicate comparable long-term survival outcomes between the two surgical approaches (39). However, the equivalence of surgical approaches regarding oncological efficacy and long-term prognosis remains debated. A Japanese retrospective study from the Osaka International Cancer Institute reported divergent conclusions. Their analysis demonstrated significantly superior 3-year disease-free survival (DFS: 71.4%, 50.5%; P = 0.004) and overall survival (OS: 80.3%, 61.2%; P = 0.002) rates in the VATE group compared to the OE cohort (40). Current evidence indicates that VATE has overcome technical bottlenecks, and its long-term survival outcomes are comparable to those of OE. This is mainly attributed to developing of high-definition imaging systems and establishing of standardized lymph node dissection procedures. However, the heterogeneity of results from different studies suggests that the potential advantages of VATE may be influenced by multiple factors such as the surgical team’s experience, case selection criteria, and perioperative management strategies. Notably, although RAE does not show significant survival benefits, its precise operation characteristics may offer new solutions for dissection high-risk anatomical regions.