De-escalating surgical treatment in low stage gallbladder cancer

Gallbladder cancer is rare with an age-standardized rate of about 1.2 per 100,000. The outcomes are dependent on tumour stage, but because about half of patients have metastatic disease at presentation overall prognosis is poor with a median overall survival of 6 months in a population-based study (1).

About 60% to 70% of gallbladder cancer diagnoses are incidental and made based on the pathology of the gallbladder following cholecystectomy for benign disease (2). When such cases are staged T1a and the margins are negative for tumour, no addition treatment is indicated. In all other cases, complete staging is advised and when considererd resectable, resection of segments IVB and V is advised along with hilar lymphadenectomy by the NCCN and IHPBA-APHPBA clinical practice guidelines (3,4). This recommendation is based on the risk of residual lymph node disease of up to 21% in patients with pT1b tumours. Compared to simple cholecystectomy, extended cholecystectomy (liver resection + lymphadenectomy) is associated with lower recurrence rates and better overall survival (5,6).

Whether the liver resection adds value alongside the lymphadenectomy is heavily debated. While the guidelines recommend resection of segments IVB and V, a wedge resection of these segments is considered sufficient in an international consensus (3). For patients with pT1b tumours several studies were not able to show any benefit of any extent of liver resection compared to simple cholecystectomy (7,8). When there is no suspicion of affected nodes some authors even suggest the lymphadenectomy can be omitted, since it is not always associated with a survival benefit (8-10). Since clinical nodal staging is difficult, it is likely a strategy without lymphadenectomy will result in nodal understaging in some patients and withholding adjuvant treatment, in case that is part of the local protocol for node positive disease (5). True pT1b tumours also appear to be rare and are commonly actual pT2 tumours (11).

In contrast to pT1b disease, most series agree that lymphadenectomy should be performed in patients diagnosed with pT2 gallbladder cancer due to a survival benefit. Recent studies have however suggested that liver resection does not add a survival benefit over lymphadenectomy alone for pT2a tumours (7,12), and another study even concludes that liver resection is not or only marginally beneficial in patients with any pT2 tumour (13).

But what to do in a patient in whom T2 gallbladder cancer is diagnosed based on imaging? Is extended cholecystectomy still indicated in these patients? A recent study included patients with T2 gallbladder cancer who underwent radical cholecystectomy with or without liver resection as primary procedure. Radical cholecystectomy included resection of the cystic plate and resected lymph nodes along the cystic duct, common bile duct, and around the hepatoduodenal ligament, and the posterior superior pancreaticoduodenal nodes. A propensity score matched comparison was performed and there were no differences in disease free or overall survival between the groups (14).

All literature on surgery for gallbladder cancer is retrospective and it is likely the confounders tumour biology and patient selection influence these retrospective study results. For instance, after propensity matching there remains a higher proportion of patients in the group with only lymphadenectomy, although this was not statistically significant. Also, treatment decisions were made based on the findings at computed tomography, endoscopic and laparoscopic ultrasonographic staging. This is inherent to the study, but can be a source of bias and these staging modalities are not standard of care in all institutions.

Altogether, liver resection results in morbidity and the risk is correlated to the extent of liver resection (15). Therefore, it seems reasonable to limit the extent of surgery required without compromising oncological outcomes. For incidental gallbladder cancer stage pT1b, omitting additional surgery seems justifiable when there are negative margins and no suspicious nodes, but accurate (intraoperative) staging can be challenging with the risk of undertreatment. The same approach without liver resection can be justified for incidental pT2 disease, while the role of lymphadenectomy is more controversial in these patients, which should be weighted with the patient preference.

For non-incidental T1b gallbladder cancer simple cholecystectomy is likely sufficient in the absence of suspicious nodes. The data on pT2 disease are again more controversial, but given all data it seems reasonable to consider limiting the extent of surgery while preserving adequate oncological outcomes. One should however consider that these treatment algorithms are mostly, if not completely, based on retrospective series and that determining the extent of liver invasion pre-operatively remains challenging. Weighing the burden and risks of surgery against the expected benefits for every individual patient seems justifiable to tailor treatment to the patient preferences.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-576/coif). The authors have no conflicts of interest to declare.

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