Introduction
Gallbladder cancer (GBC) is the most common biliary tract malignancy, with substantial geographic variations in incidence and biology. Widespread use of laparoscopic cholecystectomy has increased the incidental detection of early stage disease. The incidence of GBC varies widely, with the high-risk regions being South America (Chile and Bolivia), South Asia (Northern India and Pakistan), and East Asia. Chronic cholelithiasis, porcelain gallbladder, and certain anatomical variants (e.g., pancreaticobiliary maljunction) are implicated risk factors. The increasing detection of incidental GBC following laparoscopic cholecystectomy has shifted the stage distribution toward earlier disease. This trend provides an opportunity to refine the surgical strategies for T1 GBC. Within the T1 category, T1a is confined to the lamina propria and is adequately treated with simple cholecystectomy (SC), whereas T1b invades the muscularis propria and has historically prompted consideration of radical/extended cholecystectomy (EC), typically involving regional lymph node (LN) dissection with or without hepatic resection of the gallbladder bed (wedge resection or segment IVb/V resection). The dogma favoring EC arose from the perceived risk of occult nodal disease and residual microscopic invasion of the hepatic bed. However, contemporary multicenter studies and national databases increasingly suggest that routine EC may not confer a survival advantage over SC for carefully selected T1b cases [1-4]. This review synthesizes key data on LN metastasis risk, oncological outcomes by surgical extent, morbidity, and contemporary guidelines and proposes a disciplined, risk-adapted algorithm for clinical decision making.
Pathology, staging, and sources of heterogeneity
Accurate pathological staging is essential for operative decision making. In the American Joint Committee on Cancer, 8th edition, T1b denotes invasion of the muscularis propria without extension into the perimuscular connective tissue. Distinguishing T1a from T1b can be challenging in thin-walled gallbladder specimens, particularly in the presence of chronic cholecystitis or Rokitansky–Aschoff sinuses. Interobserver variability and variable sampling depth contribute to stage migration. The rate of occult perimuscular invasion can be reduced through meticulous grossing and step sectioning. The histopathological risk factors associated with adverse outcomes include poor differentiation, lymphovascular invasion (LVI), perineural invasion (PNI), and positive surgical margins. Crucially, modern series with standardized pathology reviews often report lower LN metastasis rates than earlier studies, helping to explain the shift in conclusions regarding the necessity of EC in patients with T1b disease [1,2].
Incidental versus non‑incidental T1b cancer
A significant proportion of T1b cancers are diagnosed incidentally after cholecystectomy for presumed benign disease. In these cases, the index operation frequently achieves an R0 resection. When adverse features are absent (negative margins, favorable grade, and no LVI/PNI), several cohorts have suggested that SC alone yields excellent long-term disease-free survival, comparable to that observed after EC [1]. Conversely, clinically suspected or radiologically evident T1b lesions may carry a higher probability of understaging or adjacent hepatic infiltration. In this context, some surgeons favor EC, particularly when cross-sectional imaging or intraoperative assessment raises concern for T2 extension or nodal disease.
Risk of LN metastasis in T1b
Meta-analytic estimates place LN metastasis in T1b at approximately 10%–11%, compared to approximately 2% in T1a, However, reported values range widely, from 0% in rigorously re-reviewed institutional series to much higher outliers in some single-center cohorts (Table 1) [2-4]. The sources of heterogeneity include pathological sampling intensity, definitional differences across editions of the staging manuals, and era effects. In a large institutional study with strict serial sectioning (5-mm intervals), LN metastasis was not detected among the analyzed nodes in T1b, and long-term disease-free survival rates exceeded 90%, irrespective of SC vs. EC [3]. Importantly, the risk is not uniform; a higher grade, LVI/PNI, and larger tumor size are associated with increased odds of nodal spread. As the baseline probability of LN metastasis is relatively low, routine nodal dissection may be unnecessary in many cases. When adverse pathological features are absent, a selective approach rather than a routine approach is reasonable.
Accurate nodal staging is prognostically important. Several guidelines suggest that a minimum of six nodes should be retrieved for adequate staging. In T1b disease, because the baseline nodal risk is relatively low, the incremental therapeutic value of extensive lymphadenectomy remains debatable. Selective nodal sampling or focused dissection may be reasonable in low-risk incidental cases, whereas comprehensive dissection remains prudent in the presence of high-risk histological findings or radiological suspicion. High-quality contrast-enhanced comtuted tomography (CT) or magnetic resonance imaging is standard for diagnosis and LN staging. Positron emission tomography/CT may assist in excluding occult distant disease in equivocal cases, although its routine use has not yet been established. Endoscopic ultrasound can be used to delineate the depth of invasion in selected settings. Intraoperative assessment using frozen-section margin analysis (cystic duct and hepatic bed) is essential when considering a step-up resection strategy. However, despite these advances in imaging, prediction of LN metastasis, particularly in the early stages, remains limited.
Oncological outcomes: SC vs. EC
EC usually entails either a non-anatomical wedge resection of the gallbladder bed or a formal bisegmentectomy (IVb/V) combined with regional lymphadenectomy (hepatoduodenal ligament stations including the cystic duct (12c), pericholedochal (12b), common hepatic artery (8), and retropancreatic (13) nodes). The goals are to clear potential microscopic hepatic invasion along the gallbladder bed and stage/treat the nodal disease.
Multiple data sources have compared SC and EC for T1b. The largest international multicenter analysis (14 centers across Asia and the Americas) reported no difference in 5‑year disease-specific survival (93.7% vs. 95.5%) or recurrence between SC and EC (Table 2) [1]. Similarly, a National Cancer Database analysis found no overall survival advantage for EC over SC in pathologic T1b, supporting the safety of SC in appropriately selected patients [5]. A 2025 Chilean multicenter series (1988–2023) of 129 patients with T1b disease observed an overall 5‑year survival of approximately 83% and no survival difference according to resection extent [6]. Meta-analyses have yielded mixed results, with some detecting short-term advantages for EC in selected contexts; however, consistent long-term superiority has not been established, especially when high-quality pathology, margin negativity, and careful selection are ensured [7].
Perioperative morbidity and quality of liver considerations
EC requires LN dissection, and in some cases, hepatic parenchymal transection or bile duct resection. Consequently, the operative time and blood loss tend to increase, and the risks of bile leak, liver failure, and infectious complications may also increase. In the absence of a clear survival benefit, the additional morbidity and recovery burden are weighed against routine EC for all patients. Although radical surgery extends the scope of surgery compared to SC, potentially increasing the risk associated with a more extensive procedure and leading to concerns regarding poorer postoperative quality of life, evidence supporting these concerns remains inconclusive. However, the tradeoff between the potential but unproven benefits of EC and the concrete risks of additional surgery must be discussed transparently. In particular, older or comorbid patients may derive a greater net benefit from SC alone, with vigilant surveillance in the absence of adverse features.
Recently, laparoscopic or robotic radical cholecystectomies have been reported to have acceptable perioperative outcomes in experienced centers. Minimally invasive radical approaches are feasible in expert hands and may attenuate morbidity; however, their incremental oncological value in strictly defined T1b, over and above SC, remains unproven [8,9]. Minimally invasive surgery offers advantages over open procedures, including reduced surgical complications and faster postoperative recovery. Given the current limitations in accurately assessing the T stage or LN metastasis through preoperative imaging and even intraoperative frozen biopsy, many cases still require a two-stage surgery. Therefore, the advancement of minimally invasive surgical techniques may enable a more proactive adoption of one-stage EC, even for early GBC, particularly T1b disease.
Guideline recommendations and practice patterns
The guidelines diverge for T1b. The Japanese Society of Hepato-Biliary-Pancreatic Surgery 2019/2021 English 3rd edition permits SC when invasion is strictly confined to the muscularis propria and other adverse features are absent, reflecting Japanese surgical experience and meticulous pathology [10]. In contrast, some Western guidelines (e.g., the National Comprehensive Cancer Network) continue to list radical resection with portal lymphadenectomy for T1b disease [11]. The European Society for Medical Oncology (ESMO) 2024 interim update, the 2024 Pan-Asian-adapted ESMO guidelines and Korean guideline emphasize individualized, multidisciplinary decision-making that incorporates comorbidities, radiologic staging, margin status, and available expertise [12-14]. Therefore, national and institutional practice patterns vary, but the convergent theme is risk adaptation rather than the universal application of EC (Table 3).
Special scenarios
When the margins in the cystic duct or hepatic bed are positive, re-resection with EC is appropriate to achieve R0 resection. In the presence of adverse histological features such as poor differentiation or LVI/PNI, EC should be considered because of the higher risk of nodal metastasis. In cases of incidental pT1b with R0 and no high-risk features, observation after SC with careful counseling and surveillance is defensible [1,3].
Proposed treatment algorithm
We propose the following pragmatic algorithm synthesizing current evidence: (1) confirm pathologic staging with expert re‑review; (2) if incidental pT1b with R0 resection and no high‑risk features is observed, discuss observation vs. targeted nodal evaluation; (3) if positive margin, adverse pathology, or clinical suspicion of nodal/T2 disease are present, perform EC with regional lymphadenectomy in fit patients; and (4) engage the patient in shared decision making regarding the tradeoff between modest, uncertain oncological gains and the tangible perioperative risks of EC [1-7,15-18] (Fig. 1).
Limitation of the evidence and future directions
The literature is dominated by retrospective studies with inherent selection bias. Randomized trials are unlikely due to the rarity of this disease. Cohort heterogeneity (incidental vs. clinical presentation, variable pathology, and surgical era effects) complicates cross-study comparisons. Prospective registries with standardized pathology, rigorous nodal mapping, and incorporation of molecular features are needed. Sentinel node strategies, ultra-staging, and ctDNA-guided surveillance merit evaluation. Health‑economic analyses and quality‑of‑life endpoints are critical to determine the true net benefit of EC in T1b.
Conclusion
Across multiple cohorts and guideline frameworks, routine EC for all T1b tumors has not been consistently supported. When the margins are negative and high-risk histopathological features are absent, SC appears to be oncologically sufficient in many patients. Selective escalation to EC is most defensible in the presence of positive margins, aggressive histology, LVI/PNI, or convincing radiological suspicion of a higher T-stage or nodal disease. A structured, multidisciplinary, and patient-centered approach should guide the extent of surgery.
PDF Links
PubReader
ePub Link
XML Download
Full text via DOI
Download Citation
