Robotic Liver Resection for Breast Cancer Metastasis: A Multicenter Case Series and Literature Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

A brief summary: 

This is a multi-center retrospective study evaluating the safety and efficacy of robotic liver resection in breast cancer with liver metastasis. This is the first study of its kind in the literature, demonstrating that the approach is both feasible and safe. 

General concept comments:

1. Follow-up duration and long term outcomes:

The follow-up duration is not clearly defined, making it difficult to assess long-term outcomes. Although the study period spans from 2011 to 2023, it’s unclear how long patients were followed after surgery. Mortality is only reported at 90 days, and the timing of recurrence is not clearly defined. It would be helpful to specify when recurrence occurred and provide recurrence and mortality rate at defined intervals (e.g., 1, 5, and 10 years).

2. Criteria for liver resection:

The criteria for selecting patients for resection are not well described. Specifically, it would be useful to clarify whether there was a tumor size or number of lesions threshold. 

3. Results table:

In the results table, it would be informative to include the range (in addition to the mean) for the variables such as number of lesions, tumor size, age etc. This would provide better insight into the variability within the cohort. 

Specific comments: 

Table 1:

For consistency and clarity, I recommend listing both the number and percentage for categorical variables (e.g., “Previous open abdominal surgery, n (%)” → “9 (25.71%)”).

Table 3:

The variable “Conversion to laparoscopy” seems incorrect. Conversions typically refer to procedures that begin laparoscopically and are converted to open. Converting from open to laparoscopy is not standard practice and may need clarification or correction.

for all table:

Percentages should use decimal points (e.g., 42.85%, not 42,85%)

 

Thank you

Author Response

Comments 1: A brief summary: 

This is a multi-center retrospective study evaluating the safety and efficacy of robotic liver resection in breast cancer with liver metastasis. This is the first study of its kind in the literature, demonstrating that the approach is both feasible and safe. 

General concept comments:

1. Follow-up duration and long term outcomes:

The follow-up duration is not clearly defined, making it difficult to assess long-term outcomes. Although the study period spans from 2011 to 2023, it’s unclear how long patients were followed after surgery. Mortality is only reported at 90 days, and the timing of recurrence is not clearly defined. It would be helpful to specify when recurrence occurred and provide recurrence and mortality rate at defined intervals (e.g., 1, 5, and 10 years).

2. Criteria for liver resection:

The criteria for selecting patients for resection are not well described. Specifically, it would be useful to clarify whether there was a tumor size or number of lesions threshold. 

3. Results table:

In the results table, it would be informative to include the range (in addition to the mean) for the variables such as number of lesions, tumor size, age etc. This would provide better insight into the variability within the cohort. 

Specific comments: 

Table 1:

For consistency and clarity, I recommend listing both the number and percentage for categorical variables (e.g., “Previous open abdominal surgery, n (%)” → “9 (25.71%)”).

Table 3:

The variable “Conversion to laparoscopy” seems incorrect. Conversions typically refer to procedures that begin laparoscopically and are converted to open. Converting from open to laparoscopy is not standard practice and may need clarification or correction.

for all table:

Percentages should use decimal points (e.g., 42.85%, not 42,85%)

 

Thank you

Response 1: Dear reviewer, thank you for your thorough and detailed work. As requested, I have made the following changes:
- I have included the mean and median values for follow-up and disease-free survival in the tables and added a comment referring to these in the results. With regard to mortality, I have specified that only one patient died during the follow-up period, and in any case within 90 days of surgery.
- In the results, in the paragraph dedicated to the type of resections performed, I have specified why it was decided to perform certain types of resections.
- ‘Conversion to laparoscopy’ refers to the conversion from a robotic approach to a laparoscopic approach, which has never occurred, demonstrating that if there are problems in robotic surgery that require conversion, it is done using an open approach rather than a laparoscopic one.
- Finally, I have modified the tables as requested.
Thank you for your work, and I hope that these changes, together with those reported by the other reviewers, will lead to the publication of this paper, which we believe to be unique in its kind.
Kind regards.

Reviewer 2 Report

Comments and Suggestions for Authors

The topic of the article is of great relevance and interest to clinicians and researchers.

The authors have highlighted the advantages of robotic surgery used for the treatment of liver metastases from breast cancer.

The entire methodology and results are clearly presented and explained.

The discussions compare the results obtained by the authors with those published in the literature and highlight the advantages and limitations of the method and study.

In the discussion chapter, the authors can also refer to the improvement of the preoperative assessment of the bleeding risk, especially in patients who also have chronic liver diseases, with a degree of liver dysfunction, including hepatopriv syndrome. Unfortunately, the classic tests used to explore the intrinsic and extrinsic pathways of coagulation (APTT and INR) do not estimate the bleeding or thrombotic risk with sufficient accuracy. Therefore, it would be advisable to resort to the preoperative study of thrombin generation or coagulation using thromboelastography in these patients, although these methods also have their limitations (the study of thrombin generation is not standardized and currently validated target levels in cirrhotic patients are missing for both methods), but progress is expected in this field as well. There are studies that have found that thrombin generation decreases with the progression of liver fibrosis (Vecerzan L, Maniu I, Cioca G. Correlation Between Thrombin Generation and Hepatic Fibrosis in Chronic Liver Diseases. Cureus. 2024 Oct 13;16(10):e71376. doi: 10.7759/cureus.71376). Thromboelastography (TEG) is a whole blood viscoelastic test which globally reflects changes in the haemostatic system, and its utility in evaluating patients with liver disease is increasingly recognised. TEG can reflect the haemostatic status of liver diseases more comprehensively than conventional coagulation tests. It has the potential to assess the severity of liver diseases, predict the risk of bleeding and death in patients with liver disease and guide blood product transfusion (He Y, Yao H, Ageno W, Méndez-Sánchez N, Guo X, Qi X. Review article: thromboelastography in liver diseases. Aliment Pharmacol Ther. 2022 Aug;56(4):580-591. doi: 10.1111/apt.17080).

There are a few small grammatical errors, which need to be corrected [e.g. ”model for BCLM compost da 5 steps: (1) intravasation: invasive breast cancer cells in...” (line 195) or ”La Stereotactic Body Radiation Therapy (SBRT) e la Interstitial Brachytherapy (BT) are two options…” (line 230)].

The bibliography is very inhomogeneous. It should be written according to the journal’s recommendations.

The article makes an important contribution to the knowledge of the advantages and limitations of robotic surgery in this field of oncology. I propose that the article need a minor revision.

Author Response

Comments 2: The topic of the article is of great relevance and interest to clinicians and researchers.

The authors have highlighted the advantages of robotic surgery used for the treatment of liver metastases from breast cancer.

The entire methodology and results are clearly presented and explained.

The discussions compare the results obtained by the authors with those published in the literature and highlight the advantages and limitations of the method and study.

In the discussion chapter, the authors can also refer to the improvement of the preoperative assessment of the bleeding risk, especially in patients who also have chronic liver diseases, with a degree of liver dysfunction, including hepatopriv syndrome. Unfortunately, the classic tests used to explore the intrinsic and extrinsic pathways of coagulation (APTT and INR) do not estimate the bleeding or thrombotic risk with sufficient accuracy. Therefore, it would be advisable to resort to the preoperative study of thrombin generation or coagulation using thromboelastography in these patients, although these methods also have their limitations (the study of thrombin generation is not standardized and currently validated target levels in cirrhotic patients are missing for both methods), but progress is expected in this field as well. There are studies that have found that thrombin generation decreases with the progression of liver fibrosis (Vecerzan L, Maniu I, Cioca G. Correlation Between Thrombin Generation and Hepatic Fibrosis in Chronic Liver Diseases. Cureus. 2024 Oct 13;16(10):e71376. doi: 10.7759/cureus.71376). Thromboelastography (TEG) is a whole blood viscoelastic test which globally reflects changes in the haemostatic system, and its utility in evaluating patients with liver disease is increasingly recognised. TEG can reflect the haemostatic status of liver diseases more comprehensively than conventional coagulation tests. It has the potential to assess the severity of liver diseases, predict the risk of bleeding and death in patients with liver disease and guide blood product transfusion (He Y, Yao H, Ageno W, Méndez-Sánchez N, Guo X, Qi X. Review article: thromboelastography in liver diseases. Aliment Pharmacol Ther. 2022 Aug;56(4):580-591. doi: 10.1111/apt.17080).

There are a few small grammatical errors, which need to be corrected [e.g. ”model for BCLM compost da 5 steps: (1) intravasation: invasive breast cancer cells in...” (line 195) or ”La Stereotactic Body Radiation Therapy (SBRT) e la Interstitial Brachytherapy (BT) are two options…” (line 230)].

The bibliography is very inhomogeneous. It should be written according to the journal’s recommendations.

The article makes an important contribution to the knowledge of the advantages and limitations of robotic surgery in this field of oncology. I propose that the article need a minor revision.

Response 2:

Dear reviewer, thank you for your excellent work and for your appreciation of our paper. I have reviewed the grammar and corrected some glaring errors that had escaped our review. Regarding the risk of bleeding, we did not include it in the discussion because we think it could be misleading with regard to the main topic of the article. However, blood loss is the subject of a study we are currently publishing.
Thank you for your work, and I hope that these changes, together with those reported by the other reviewers, will lead to the publication of this paper, which we believe to be unique in its kind.
Kind regards.

Reviewer 3 Report

Comments and Suggestions for Authors

The topic of liver resection of breast cancer liver mets had not been studied much in the past due to the assumption that the prognosis is poor. However, as mentioned in the study, the same was noted with colorectal liver mets resection which is now considered part of best practice. The aim was clearly stated that the study was to analyse the feasibility of robotic liver resection on breast cancer mets.

It is a retrospective study and so as mentioned has limitations. It could also be added that the number of cases in this study is small (only 35 cases) and there is no long-term data eg survival rates etc.

A question for the authors would be, is there a maximal number of mets that they would not operate on? or a maximal size or a maximal degree of hepatectomy? Historically, colorectal mets resection was limited by several criteria and it would be interesting if there is such limits for breast cancer mets in the infancy of liver resection for breast cancer.

There was a mention of 20% recurrence rate. What was the interval of follow up? What was the progression free survival? 

A few typos of note:

1. line 74 - HCC was mentioned - should it be BCLM?
2. Line 122 - 2310.28 min of operative time - should it be 210.28 ?
3. line 195 - 'da'?

Otherwise, this is an area that certainly needs more work on.

good effort.

Author Response

Comments 3:

The topic of liver resection of breast cancer liver mets had not been studied much in the past due to the assumption that the prognosis is poor. However, as mentioned in the study, the same was noted with colorectal liver mets resection which is now considered part of best practice. The aim was clearly stated that the study was to analyse the feasibility of robotic liver resection on breast cancer mets.

It is a retrospective study and so as mentioned has limitations. It could also be added that the number of cases in this study is small (only 35 cases) and there is no long-term data eg survival rates etc.

A question for the authors would be, is there a maximal number of mets that they would not operate on? or a maximal size or a maximal degree of hepatectomy? Historically, colorectal mets resection was limited by several criteria and it would be interesting if there is such limits for breast cancer mets in the infancy of liver resection for breast cancer.

There was a mention of 20% recurrence rate. What was the interval of follow up? What was the progression free survival? 

A few typos of note:

1. line 74 - HCC was mentioned - should it be BCLM?
2. Line 122 - 2310.28 min of operative time - should it be 210.28 ?
3. line 195 - 'da'?

Otherwise, this is an area that certainly needs more work on.

good effort.

 

Comments 3:
Dear reviewer, thank you for your comments and appreciation. As you suggested, I have included in the limitations of the study that the study cohort is small and that the follow-up data are not so long-term. I have also revised the grammar of some glaring errors that were missed in the first review and included data on follow-up and disease-free survival. Regarding the maximum degree of hepatectomy, we also performed major hepatectomies and I have specified, in the dedicated paragraph within the results, the reason why we performed them. Regarding the maximum number of metastases that we would not operate on, we think that this could lead to a long and misleading explanation in the discussion, as there are still no guidelines on this and, being a multicentre study, there is a degree of freedom of execution that depends on the surgeon in question.
Thank you for your work, and I hope that these changes, together with those reported by the other reviewers, will lead to the publication of this paper, which we believe to be unique in its kind.
Kind regards.

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript presents a timely and well-organized multicenter case series addressing the feasibility and safety of robotic liver resection for breast cancer liver metastases (BCLM). The topic is of high clinical relevance, and the study is methodologically sound, supported by an extensive literature review and clearly described results. The authors appropriately highlight the growing interest in surgical treatment of oligometastatic disease and justify the role of robotic-assisted liver surgery in carefully selected patients. The retrospective nature and limited sample size are acknowledged as limitations, yet the strength of multicenter collaboration adds significant value.

Some minor revisions are recommended to improve the manuscript’s clarity and impact. First, while the intraoperative and postoperative outcomes are well detailed, the operative time statistics (mean 210.28 min vs. median 180 min) appear misrepresented in Table 3 and should be double-checked for accuracy. Additionally, a few typographical inconsistencies (e.g., misplaced commas in percentages or number formats) should be corrected throughout tables and text. It would also strengthen the discussion to briefly comment on the potential role of patient molecular subtypes (e.g., HER2, ER/PR status) in guiding surgical candidacy or outcomes, as this information is touched upon in the background but not integrated into the presented data. Overall, this is a well-conducted and relevant study, and minor revisions are needed.

Author Response

Comments 4:

The manuscript presents a timely and well-organized multicenter case series addressing the feasibility and safety of robotic liver resection for breast cancer liver metastases (BCLM). The topic is of high clinical relevance, and the study is methodologically sound, supported by an extensive literature review and clearly described results. The authors appropriately highlight the growing interest in surgical treatment of oligometastatic disease and justify the role of robotic-assisted liver surgery in carefully selected patients. The retrospective nature and limited sample size are acknowledged as limitations, yet the strength of multicenter collaboration adds significant value.

Some minor revisions are recommended to improve the manuscript’s clarity and impact. First, while the intraoperative and postoperative outcomes are well detailed, the operative time statistics (mean 210.28 min vs. median 180 min) appear misrepresented in Table 3 and should be double-checked for accuracy. Additionally, a few typographical inconsistencies (e.g., misplaced commas in percentages or number formats) should be corrected throughout tables and text. It would also strengthen the discussion to briefly comment on the potential role of patient molecular subtypes (e.g., HER2, ER/PR status) in guiding surgical candidacy or outcomes, as this information is touched upon in the background but not integrated into the presented data. Overall, this is a well-conducted and relevant study, and minor revisions are needed.

 

Response 4:

Dear reviewer, thank you for your comments and appreciation. As you suggested, I have made corrections to the data in the tables (commas and number formats) and we have double-checked the data. I have also included the absence of data on the biology of primary breast tumours within the limitations. However, we are integrating this data into a prospective database for new cases in order to carry out a new, more accurate investigation with comprehensive data, including breast pathology, to strengthen the discussion.
Thank you for your work, and I hope that these changes, together with those reported by the other reviewers, will lead to the publication of this paper, which we believe to be unique in its kind.
Kind regards.