Response to commentary: “Propofol-based total intravenous anesthesia and recurrence-free survival after hepatectomy-does it improve outcomes?”

We thank Drs. Zhou and Gabriel for their thoughtful commentary on our study and for placing our findings within the broader context of the literature on anesthetic technique and oncologic outcomes (1).

We agree with the commentators that the question of whether anesthetic choice meaningfully influences cancer recurrence remains unresolved. As they rightly point out, retrospective studies—even large ones—are inherently limited by residual confounding, and the existing randomized controlled trial (RCT) evidence, including our own, has so far not demonstrated a clear survival benefit of propofol-based total intravenous anesthesia (TIVA) over volatile anesthesia in the short term.

The commentators highlighted the open surgery subgroup finding as a potentially important signal. We share their interest in this observation. In our study, TIVA was associated with a significantly lower hazard of recurrence or death among patients undergoing open hepatectomy [hazard ratio (HR) 0.49, 95% confidence interval (CI): 0.25–0.95], whereas no such association was seen in the laparoscopic group. We have proposed that this difference may reflect the greater surgical stress and immune perturbation associated with open procedures, creating a more favorable environment for the immunopreserving and anti-tumor properties of propofol to manifest. However, we wish to emphasize, as we did in the original paper, that this subgroup analysis was post hoc and the study was not powered for this comparison. The finding should therefore be interpreted with caution and requires prospective validation in a dedicated trial.

The commentators also noted that the current publication reports only 1-year outcomes, while the study was originally designed with a 3-year follow-up as a prespecified secondary endpoint. We can confirm that long-term follow-up data are being compiled and will be reported in due course. We anticipate that the 3-year outcomes will provide important additional insight, particularly with respect to late recurrence, which may be more susceptible to the immunomodulatory effects of anesthetic agents.

Finally, we concur with the commentators’ call for further large RCTs, particularly in the setting of major open cancer surgery and in cancer types with distinct immunologic or metastatic profiles. Our study contributes level I evidence for hepatocellular carcinoma undergoing predominantly laparoscopic resection, and we hope it will help frame the design of future trials that are specifically powered to address subgroup questions that remain open.

We thank the editorial team at Annals of Translational Medicine for the opportunity to respond.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Translational Medicine. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-2026-0113/coif). The authors have 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. Zhou YQ, Gabriel RA. Propofol-based total intravenous anesthesia and recurrence-free survival after hepatectomy-does it improve outcomes? Ann Transl Med 2026;14:21. [Crossref] [PubMed]