A commentary on ‘Significance of anatomical resection and resection margin status in patients with HBV-related hepatocellular carcinoma and microvascular invasion: a multicenter propensity score-matched study’

Dear Editor,

We have read with great interest the article by Dr Zhang et al. ¹. They performed a multicenter propensity score-matched study, and the results of their study showed that anatomical resection (AR) with wide resection margin (RM) was associated with the best survival outcomes in patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) after hepatectomy. Wide RM resulted in a significantly lower RM recurrence rate than narrow RM, regardless of whether the patient was in the AR or nonanatomical resection (NAR) group. If technically feasible and safe, AR with wide RM is the best therapeutic strategy for HCC patients who are estimated to have a high risk of MVI using the currently available preoperative predictive models. Although this study was well-designed and high-quality, we would like to raise the following comments:

First, in the ‘Postoperative follow-up’ section, the authors defined recurrence-free survival (RFS) as ‘the time from date of liver resection (LR) to the time of tumor recurrence’, and ‘patients with no recurrent disease were censored at the last time at which they were known to be recurrence free’. However, the description mentioned above is not the generally-recognized definition of RFS but is always regarded as the definition of time to recurrence (TTR). Actually, in most previous studies, RFS is generally defined as ‘the time from date of curative surgery to the time of recurrence or death’. In other words, if a patient died without recurrence in the follow-up after surgery, it should be considered as an endpoint for RFS but not a censored event. For example, one male patient died of decompensated cirrhosis in the 10th month after resection of HCC, but recurrence did not occur at the time of death. For this patient, the RFS should be considered as having an endpoint event (defined as ‘1’), while the TTR should be considered as a censored event (defined as ‘0’). Although the time of RFS and TTR is the same (10 months), it was totally different between the two final events. Thus, we hope that the authors need to distinguish the two concepts or redefine RFS.

In addition, propensity score matching (PSM) analysis has been generally used in retrospective observational studies, which enables better balance between groups across all potential risk factors and evaluates the extent of balanced match in a measurable approach^2,3. However, how the authors select variables for matching, or which variables are included in the matching, are not mentioned in the ‘Statistical analysis’ section of this paper. Different variables included in the matching will affect the matched samples, thus affecting the results. Therefore, we suggest that the authors add them to the corresponding part of the article.

Furthermore, postoperative adjuvant therapy can significantly improve the prognosis of HCC patients with MVI⁴, especially since most of the patients included in the study underwent NAR with wide or narrow RM. And the authors did not state whether the included patients received adjuvant therapy or not.

Last but not least, since the included patients were all treated by LR, it would be better to list the variables related to surgery. For example, duration of operation, intraoperative blood loss, requirement of transfusion, postoperative severe complications, length of hospital stay, and perioperative mortality should be included in this study.

In summary, clarification regarding these issues would greatly solidify the conclusions of the study by Dr Zhang et al.

Ethical approval

Not applicable.

Consent

Not applicable.

Sources of funding

The comment does not receive any funding.

Author contribution

S.Y.: study design and writing; C.X. and Z.M.: critical review; S.Y.: study supervision.

Conflicts of interest disclosure

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Shiye Yang and Chunqiu Xia.

Data availability statement

Not applicable.

Provenance and peer review

This manuscript was not an invited paper.