Robotic versus Open Surgery in Locally Advanced Non-Small Cell Lung Cancer: Evaluation of Surgical and Oncological Outcomes

Round 1

Reviewer 1 Report

Dear Authors, the article is well written and the case history is relevant, but in my opinion, if the aim of the study is also to assess oncologic outcomes, a propensity score between the two populations should be considered. As described, the two patient groups are nonhomogeneous, with a predominance of T1-T2 in patients undergoing robotic surgery, and a predominance of T3-T4 in patients undergoing open surgery. This may represent a selection bias. 

Author Response

Dear Reviewer,

Thank you for your interesting comment. We have evaluated this possible selection bias and according to the analysis performed by the Statistician, we have obtained:

Robotic surgery vs OS adjusted for T stage (T1+T2, T3+T4): p=0.888

Robotic surgery vs local recurrence-free survival adjusted for T stage (T1+T2, T3+T4): p=0.562

Robotic surgery vs metastasis-free survival adjusted for T stage (T1+T2, T3+T4): p=0.846

Reviewer 2 Report

The authors presented a retrospective analysis of locally advanced NSCLC patients treated with open surgery and robotic surgery in a tertiary cancer centre. The main study conclusion was that robotic surgery could be considered safe and feasible in locally advanced NSCLC.

The study provides new insights on the topic but has several limitations.

Major comments

1. Both groups are incomparable for treatment outcomes owing to severe stage imbalance (Stage IIIA vs. IIIB). This should be clearly stated, and figures 1-3 should be removed.
2. There is no information on perioperative therapies in both groups (preoperative and postoperative chemotherapy, postoperative radiotherapy).
3. There is no information on initial staging procedures.
4. There is no information on the number of removed lymph nodes.
5. Treatment complications should be presented in detail in the table.
6. Data from early NSCLC indicate that robotic surgery seems to be more expensive and is associated with longer operating times than conventional VATS: https://pubmed.ncbi.nlm.nih.gov/34165501/ ; https://pubmed.ncbi.nlm.nih.gov/24210834/. Most likely, the costs have not been captured; however, the operating times in this series were much longer with robotic surgery despite less advanced disease. This is an explicit limitation of this procedure and should strongly be addressed in the discussion.
7. The consort diagram should be presented, starting from the total number of patients operated on within the study period, the number of exclusions, etc.
8. The authors state that there was “a positive trend in surgical results after robotic surgery when compared to open surgery”. What aspect do you mean? Fig. 1 shows slightly better results in the open surgery group despite much more advanced stages.

Minor comments

1. Neoadjuvant immunotherapy will likely become a new standard in locally advanced NSCLC. This group of patients was excluded from the analysis due to anticipated side effects. However, there is no information on whether they were not subjected to robotic surgery or excluded ex-post (this would be incorrect). This aspect needs clarification and discussion.
2. The authors use the term “advanced-stage lung cancer” a few times, which may be considered a metastatic disease. Use consequently “locally advanced”.
3. What does “Figure 4” (p. 7) refer to?

1. The article necessitates professional proofreading.

Author Response

Dear Reviewer,

Thank you for taking the time to review our manuscript and for your interesting feedback

Please consider the following list explaining our answer to your comments:

• According to your suggestion, new Kaplan-Meier curves were calculated
• Information on neoadjuvant/adjuvant therapy is reported in lines 151, 175, 185 and 197.
• Details on preoperative staging are described in lines 80-86
• Characteristics of the lymphadenectomy have been inserted in Table 2
• The postoperative complications are described in the text (lines 159-161; lines 191-193)
• In the past, robotic surgery was characterized by higher cost when compared to open surgery and VATS, as reported by different papers. Over the years,the use of robotic surgery for the treatment of lung cancer has substantially increased and due to the standardization of the technique, it is cost-effective. Robotic surgery is currently associated with improved perioperative outcomes compared with vats and open surgery and, in high-volume centers, no significant cost difference is observed between these different approaches.
• The longer operative time still represents a critical point of robotic surgery. Nevertheless, the robotic approach is associated with a lower complication rate and length of hospital stay, as reported in our study, allowing to reduce postoperative costs. We have argued this point in the discussion (lines 336-343)

Patel YS, Baste JM, Shargall Y, Waddell TK, Yasufuku K, Machuca TN, Xie F, Thabane L, Hanna WC. Robotic Lobectomy is Cost-Effective and Provides Comparable Health Utility Scores to Video-Assisted Lobectomy: Early Results of the RAVAL Trial. Ann Surg. 2023 Aug 8

Nguyen DM, Sarkaria IS, Song C, Reddy RM, Villamizar N, Herrera LJ, Shi L, Liu E, Rice D, Oh DS. Clinical and economic comparative effectiveness of robotic-assisted, video-assisted thoracoscopic, and open lobectomy. J Thorac Dis. 2020 Mar;12(3):296-306

Shah PC, de Groot A, Cerfolio R, Huang WC, Huang K, Song C, Li Y, Kreaden U, Oh DS. Impact of type of minimally invasive approach on open conversions across ten common procedures in different specialities. Surg Endosc. 2022 Aug;36(8):6067-6075

• We affirm that “a positive trend was observed in surgical results after robotic surgery” as regards the postoperative outcomes. In detail, the complications rate and the length of the hospitalization were lower in the robotic group. Moreover, according to the Reviewer, we declare that “, no statistically significant differences were observed between the robotic and open groups regarding oncological outcomes”
• In our experience, a series of patients underwent surgery after neoadjuvant immunochemotherapy, mainly treated with robotic surgery. The decision to exclude these patients from this study was not based on the side effects related to the induction therapy, but rather on the better survival observed after this treatment, which would influence the analysis of the oncological results. We clarify this point in the discussion (lines 373-374)
• Advanced-stage was corrected with locally advanced
• There are only 3 figures in the paper. The explanation of the image is reported before each figure.
• The English language was revised by a native speaker doctor

Reviewer 3 Report

Dear Authors,

I read with interest the manuscript titled "Robotic versus open surgery in locally advanced non-small cell lung cancer: evaluation of surgical and oncological outcomes". The topic is timely, and comparing robotic and open outcomes in advanced NSCLC is necessary to define a more precise patient selection without clear indications.

I congratulate you on the sample size and the results obtained. Before considering the manuscript worthy of publication, I would like you to improve a few points:

1) explain what is meant by OS, DFS, local recurrence FS, and every oncological outcome you investigated. To help the reader more easily make personal conclusions about the results of your manuscript, rather than running into nerve-wracking puzzles: for example, the discrepancy between medians of FU and mean of OS in the two groups;

2) line 81: Reverse abbreviation of EBUS-TBNA with explanation in full;

3) line 84: add FDG for PET examination;

4) although you declare substantial homogeneity of characteristics between the two groups, I ask you to add a statistical evaluation in Table 1 for each feature to make the data quick to read;

5) it would be beneficial to integrate a forest plot and indicate the HR for the OS by the stratified Cox regression model for the main features shown in Table 1 and Table 2

6) You should add a censored bar in Fig. 1-3 or state the number of patients at risk and add HR considering a reference group.

7) I suggest to revise the English language

I suggest an integral manuscript revision to avoid redundancy of terminology. Prepositions need a more appropriate usage. There is an excessive use of passive verb forms. Some sentences should be shorter.  Commas should be revised.

Author Response

Dear Reviewer,

thank you for your insightful comments and feedback.

According to your comments:

• The definition of OS, FS, local recurrence-free survival and metastasis-free survival was inserted in the text (lines 113-120).
• There was no discrepancy in follow-up in our series, resulting in 70 months in the total sample (83 months in the open group and 76 in the robotic group). The section “Oncological Outcomes” is modified to clarify the concepts.
• Table 1 has been modified inserting the p-value, according to your suggestion
• The analysis of predictive factors for the OS is reported in Table 3
• The patients censored were indicated by bar
• The English language was revised by a native speaker doctor.

Round 2

Reviewer 1 Report

Dear authors, after the changes to the text, and in particular the statistical part, I believe the paper has improved, and and may be of interest to readers of the journal.

Reviewer 3 Report

Dear authors,

I thank you for the changes you have made.