Abstract
Background
Radical resection remains the cornerstone of curative-intent treatment for perihilar cholangiocarcinoma (pCCA). With the evolution of minimally invasive approaches, laparoscopic surgery (LS) and robot-assisted surgery (RAS) have been increasingly adopted in its surgical management. However, high-quality comparative evidence evaluating these approaches against conventional open surgery (OS) remains limited, and direct comparisons between LS and RAS are scarce. This systematic review and meta-analysis aimed to synthesize the available direct comparative evidence on RAS, LS, and OS for pCCA. Given the sparse evidence network and limited ability to verify the transitivity assumption, network meta-analysis was retained only as an exploratory adjunct.
Methods
A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database was performed to identify clinical studies comparing robot-assisted surgery (RAS), laparoscopic surgery (LS), and open surgery (OS). Perioperative efficacy and safety were prespecified as the primary domains of interest. Outcomes included operative time, intraoperative blood loss, intraoperative transfusion rate, length of hospital stay, hospitalization costs, Clavien–Dindo grade ≥ III complications, R0 resection rate, 1- and 2-year overall survival, and changes in liver function and nutrition-related biochemical indices, including ALT, T-BIL, and ALB. The primary quantitative synthesis was based on direct pairwise meta-analyses of head-to-head comparisons, using random-effects or fixed-effect models according to prespecified heterogeneity criteria. An exploratory network meta-analysis was performed to describe the broader comparative evidence structure, but indirect comparisons and treatment rankings were not used as the primary basis for clinical interpretation. The certainty of evidence was evaluated using the GRADE framework, with additional consideration of network-specific concerns where applicable.
Results
A total of 24 comparative studies involving 1,598 patients were included, comprising 18 LS–OS studies, five RAS–OS studies, and one direct RAS–LS study. Compared with OS, both LS and RAS were associated with significantly longer operative time, lower intraoperative blood loss, and shorter hospital stay. No clear differences were observed in intraoperative transfusion rate, R0 resection rate, 1-year overall survival, or 2-year overall survival. Neither LS nor RAS was associated with a statistically significant difference in major complications compared with OS. For RAS versus OS, the point estimate was greater than 1, but the confidence interval crossed the null value and the evidence was of very low certainty. For biochemical outcomes, LS was associated with a smaller postoperative–preoperative change in T-BIL, whereas no clear differences were observed in ALT or ALB. The single direct RAS–LS study was summarized using study-specific estimates and was not quantitatively pooled. The exploratory network analysis was generally directionally consistent with the direct pairwise evidence for several perioperative outcomes, but most outcome networks lacked a robust closed loop, and any triangular loop depended on a single small retrospective RAS–LS study. Key clinical effect modifiers, including tumor extent, Bismuth classification, vascular involvement, extent of hepatectomy, reconstruction requirements, case complexity, and surgeon or institutional experience, were incompletely reported across studies, limiting the validity of indirect comparisons. Reporting of operative extent, patient-selection criteria, surgeon experience, learning-curve status, and institutional surgical volume was incomplete and inconsistent, precluding reliable subgroup analysis or adjustment for these clinically important effect modifiers.
Conclusion
Current direct comparative evidence suggests that minimally invasive surgery may offer selected short-term perioperative benefits in carefully selected patients with pCCA, particularly reduced intraoperative blood loss and shorter hospital stay with LS. However, the optimal selection criteria for minimally invasive approaches remain undefined. However, these potential benefits should be balanced against longer operative time and the low or very low certainty of the available evidence. No surgical approach can currently be considered superior with respect to intraoperative transfusion rate, major complications, oncologic outcomes, or survival. Evidence regarding liver function and nutrition-related biochemical indices remains limited and heterogeneous. Because the evidence network was sparse and the direct RAS–LS comparison was limited to a single small retrospective study, the transitivity assumption could not be adequately supported. Accordingly, network estimates and treatment rankings should be considered exploratory and hypothesis-generating rather than confirmatory and should not be used in isolation to guide surgical decision-making. Well-designed multicenter prospective studies with standardized reporting of tumor complexity, operative extent, reconstruction requirements, and surgeon or center experience are needed.
Systematic Review Registration
https://www.crd.york.ac.uk/PROSPERO/view/CRD420261297194, PROSPERO: CRD420261297194
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