PONE-D-22-25140Oncological and Functional Outcomes of High-Risk and Very High-Risk Prostate Cancer Patients after Robot-Assisted Radical ProstatectomyPLOS ONE

Dear Dr. Jiang,

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I would like to thank the editor for this opportunity and the authors foe their efforts. Investigating the outcomes of robot-assisted radical prostatectomy outcomes based on a risk stratification method on included sample of patients and also including the impact of neoadjuvant therapy besides the surgery in this study is interesting and adds to the literature. Although the study notion is not novel, the methodology made the material interesting and highlighting the worse outcomes in high-risk patients leverages the importance of material from a clinical aspect of evaluation. The manuscript needs some revisions prior to finalization and reaching a decision. My comments and suggestions are provided below.

1. The first major concern about this manuscript is the used terms of “high-risk” and “very high-risk” patients with prostate cancer in need of surgery. The used nomenclature is not so usual in the literature in field. It is more questionable when the authors presented the results stratified by “below high-risk” and “high-risk and very high-risk”. Why not reporting the results for “low-risk” and “high-risk” patients as it is common in literature? A revision on this issue might be helpful.

2. Abstract: this section needs more information of the study methods and the definitions of study groups and outcomes in the materials and methods part, to make the following presented results clearer and easy to understand.

3. Introduction: the part on the review of previous literature and highlighting the gap in studies that is tried to be covered by this study is insufficient and needs more expansion and citation to similar previous studies.

4. Materials and Methods: The second paragraph introducing the two groups of <high and="" risk="">5. Statistical analysis: it should be clear whether the authors used “multivariate” or “multivariable” logistic regression models to investigate the predictive factors for postoperative outcomes, since these two are different methods statistically. Also, adding the log-rank test as the statistical test to compare the results of survival analysis is suggested in this part.

6. Results: some results in the tables are stratified by four risk groups and it was not mentioned in the methods what the criteria for this stratification was. One major issue about the results are the survival results presented in figure 1B. Since the provided P-value are between three recruited groups it is not clear whether the results between the high-risk groups with and without AT were significant or not. Adding another plot with only these two groups would be beneficial.

7. Discussion: although the results are compared with literature well, some studies are missed and it is suggested to included relevant studies about the results of RaRP in high-risk patients to this section (Example: Abdollah F, Sood A, Sammon JD, Hsu L, Beyer B, Moschini M, Gandaglia G, Rogers CG, Haese A, Montorsi F, Graefen M, Briganti A, Menon M. Long-term cancer control outcomes in patients with clinically high-risk prostate cancer treated with robot-assisted radical prostatectomy: results from a multi-institutional study of 1100 patients. Eur Urol. 2015 Sep;68(3):497-505. doi: 10.1016/j.eururo.2015.06.020. Epub 2015 Jun 26. PMID: 26119559.)</high>

Reviewer #2: Thanks for sending me this analytical work about prostate cancer robotic treatment. First of all congratulations to the authors for their work and achievement, I believe the aims of study are of utmost importance to the designated field but there are some major issues that need to be addressed before proceeding. Would be happy to help with revision and eventually see the paper published.

Majors:

1- The definition of risk (high, low, etc) are not defined while being used throughout the paper

2- The flow of paper (both scientific and narrative) is hard to follow. Several times I was lost in the middle of results and had to turn back and read from the beginning. In other words, the results section is not organized and is long. They may add some subsections

Minors:

1- Authors were too generous with using abbreviations. I strongly suggest using full wording as much as possible

2- I think it is MacOS Big Sur

Reviewer #3: In this paper, BCR-free survival rate as an oncological outcome and stress urinary incontinence (SUI) and Urgency Urinary Incontinence (UUI) as functional outcomes of robot assisted radical prostatectomy (RaRP) were investigated in high-risk and very high-risk prostate cancer patients and were compared to below high-risk group. The BCR-free survival of patients in high-risk and very high-risk group who also received adjuvant therapy was comparable to those in below high-risk group. Also, in long-term follow-up, the rate of SUI was not significantly different between high-risk/ very high-risk and low risk group. Suggesting that RaRP is a safe treatment option in high-risk/ very high-risk prostate cancer patients.

The paper is well-written and the content is interesting to the readers of the journal.

In my opinion, the paper could be accepted after making major/minor revisions as follows:

Major concerns

It is not clear how the patients were assessed in the selected time intervals. Was it through clinic visits?

It would be better to mention in the statistical analysis part that data was reported as mean ± SD and median (range).

As well as age, the relationship between other characteristics of the 71 patients included for SUI and UUI analysis should be mentioned.

In 5th paragraph of results: odds ratios should come with confidence intervals.

In tables 1, S1, and S2, the total columns need to be transferred before risk groups as the p-value is related to the comparison of the risk groups.

In table 2 and supplementary table 3 heading, the number of patients that were included and analyzed should be mentioned.

Heading of table 1 and S2 are similar, and their difference is unclear.

Figure 2: in the horizontal axis the interval between 0-1 months shouldn’t be equal to 1-3 months or 3-6 months.

The latest study that authors discussed and referred is for Jul 2021, there are some recent studies for example by Shin et al. on oncological and functional outcomes of RaRP that should be discussed here.

Minor concerns

For the reference [(11)] in the material and method part, [] is extra.

UUI is abbreviation for “Urge/ urgency urinary incontinence” not “urinary urgency incontinence”.

In 4th paragraph of results, after talking about 71 patients included, first the number (%) of patients in each group should be mentioned and then the age and other characteristics.

Style of reference 4 should be corrected. It’s a published paper and there is no need to mention the website.

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Reviewer #1: Yes: Sina Azadnajafabad, MD, MPH

Reviewer #2: Yes: Esmaeil Mohammadi, MD MPH

Reviewer #3: No

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Oncological and Functional Outcomes of High-Risk and Very High-Risk Prostate Cancer Patients after Robot-Assisted Radical Prostatectomy

PONE-D-22-25140R1

Dear Dr. Jiang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Mohammad-Mahdi Rashidi, M.D.

Guest Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: With many thanks, the authors have carefully addressed my comments and suggestions in this revision. I endorse this manuscript for publication in its current format.

Reviewer #2: Authors did a great job and revised the paper accordingly. I have no further suggestions at this point

Reviewer #3: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Sina Azadnajafabad, MD, MPH

Reviewer #2: Yes: Esmaeil Mohammadi, MD MPH

Reviewer #3: Yes: Niloufar Salehi

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