Is liver resection necessary for T2 gallbladder cancer?

We read with delight the manuscript titled: “Prognostic effect of liver resection in extended cholecystectomy for T2 gallbladder cancer revisited: a retrospective cohort study with propensity score-matched analysis” (1). This is a retrospective study of 150 patients from three tertiary hospitals which examines the impact of liver resection on patients with suspected gallbladder cancer (GBC) who were pathologically confirmed as stage pT2 GBC post-operatively. These cases were further subdivided by location as T2a (peritoneal side) or T2b (hepatic side).

Of 197 patients meeting inclusion criteria, 100 patients with lymph node dissection and liver resection (LND+L) were matched 2:1 to 50 patients with lymph node dissection only (LND). The outcomes of interest were frequency of disease recurrence, and length of disease-free survival. There is potential bias between these groups since for one hospital decisions regarding liver resection were based on preoperative evaluation of imaging work-up, whereas liver resection was routinely performed at the two other hospitals. Other unmeasured hospital characteristics may differentially affect not only case selection but also patient selection, other non-surgical treatment, and follow-up.

Prior to propensity score matching (PSM) these two groups were found to differ significantly by age, operative method (open vs. laparoscopic/robotic), T stage (T2a vs. T2b), and frequency of adjuvant treatment, specifically concurrent chemoradiotherapy. These differences were significantly different based on a P value of P<0.05 (Tab. 1). The authors note that these differences were non-significant after PSM, except for operative method, which remained significant after matching. This information was reported in the “Results-Patient characteristics”. However, earlier in the manuscript under the “Method-Study population” section, the authors write that propensity score “matching factors included age, sex, operative method, T stage, LN metastasis, and adjuvant treatment”. We note that in Tab. 1 there is no significant difference between LND+L and LND groups for sex (P=0.066), or for LN metastasis (P=0.188), so it is unclear if these two additional variables were used for determining matching in the final results. As PSM is included in the study title, it is disappointing that the variables used for the matching process are not more clearly indicated.

The goal of PSM is to compare untreated units to treated units, as if the treatment has been fully randomized, conditional on observable characteristics common to both groups. PSM usually requires very large samples, and the matching for this study started with a sample of only 197 eligible cases produced from a total of 329 cases diagnosed with pT2 GBC. Considering that this study was (I) unable to successfully match cases on operative method, which would have been indicated by a non-significant group difference post-matching, and that (II) two of three hospitals routinely applied liver resection to pT2 GBC cases, one may question whether the conclusion of this study is valid, namely, that liver resection is ineffective in affecting disease recurrence or disease-free survival. We believe that the application of PSM in this study, based on the small sample size, may have been less-than-ideal method for comparing the groups. We believe the study may have had more statistical power to detect a significant group difference in outcomes between LND+L and LND alone if the authors had used all cases meeting selection criteria before the application of PSM. The use of PSM in this study weakens rather than enhances the validity of the results observed. The variables on which groups differed, such as age or T stage could have been controlled for by applying multivariable analysis without using PSM. Hence, while the study concludes by saying that liver resection is not necessary and it is the LN disease that determines longevity, we are not entirely convinced that evidence fully lines up based on this sample size and the variables compared.

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: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-586/coif). G.S. has stock in a company: Exilio, but none to do with this publication. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Park Y, Lee JS, Lee B, et al. Prognostic Effect of liver resection in extended cholecystectomy for T2 gallbladder cancer revisited: a retrospective cohort study with propensity score-matched analysis. Ann Surg 2023;278:985-93. [Crossref] [PubMed]