PONE-D-21-03241

Risk of adverse pathological features for intermediate risk prostate cancer: clinical implications for definitive radiation therapy

PLOS ONE

Dear Dr. Zhang,

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We look forward to receiving your revised manuscript.

Kind regards,

Qinghui Zhang

Academic Editor

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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: 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

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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

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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: This is a well-written retrospective review of patients who underwent definitive surgery for intermediate risk prostate cancer. The study highlights the importance of adequate pre-clinical staging and demonstrates further benefit for the use of MP-MRI prior to definitive-intent treatment. The statistical analysis have been performed appropriately, and the author's conclusions are supported by them.

Minor stylistic/grammar comments:

1) Consider rewording "Per NCCN guidelines, intermediate risk prostate cancer (PCa) has been defined as having at least one of the following features: cT2b to cT2c, Gleason score (GS) 7 (3+4/4+3), and PSA 10 to 20 ng/ml." as "According to guidelines published by the National Comprehensive Cancer Network (NCCN), intermediate risk prostate cancer (PCa) is defined as having at least one of the following features: cT2b to cT2c, Gleason score (GS) 7 (3+4/4+3), and PSA 10 to 20 ng/ml."

2) Consider rewording "For men receiving definitive curative intent radiotherapy (RT), the success of treatment relies on accurately defining the target volume in order to ensure disease control and reduce toxicity. Recent technology improvement in treatment planning and delivery with image guidance and intensity-modulated RT has improved treatment precision by reducing the treatment margins, therefore limiting radiation dose to surrounding normal tissues. However, the reduction of margins without considering the pattern and extent of microscopic spread of disease may negatively influence the outcome." to "For men receiving curative-intent radiotherapy (RT), treatment success relies on accurate delineation of target volumes. Recent technology improvement in treatment planning and delivery with image guidance and intensity-modulated RT has improved treatment precision by reducing the treatment margins, therefore limiting radiation dose to surrounding normal tissues. However, the reduction of margins without considering the pattern and extent of microscopic spread of disease may negatively influence outcomes."

Minor comments:

1) Please describe pre-treatment workup in greater detail in the Methods section. In the discussion, it is stated that *none* of the patients underwent MP-MRI prior to treatment. Did pre-treatment work-up solely consist of rectal exam, PSA, and TRUS biopsy/findings? This is crucial to the results of the study.

2) In the discussion section, I recommend further discussion on the utility of MP-MRI, including rates of upstaging from these studies.

Overall, the study is well done, and merits publication in a journal.

Reviewer #2: A retrospective review addressing a clinically significant question. A Well written, easy read, and statistically sound manuscript. The format of data presentation in figures is right but needs editing/ improvement. The first two figures look busy and difficult to follow. The authors acknowledge the study's limitations and gaps in the data collection, not an uncommon problem in retrospective studies. This will be an excellent addition to the existing literature in the context of uncertainties of clinical staging and delineation of CTV in intermediate-risk prorate cancer patients.

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Reviewer #1: No

Reviewer #2: Yes: Naseer Ahmed, MD, FRCPC

Radiation Oncologist, Associate Professor, Max Rady College of Medicine, Faculty of Health Sciences, Department of Radiology, Section of Radiation Oncology, University of Manitoba

Affiliate Scientist, Research Institute in Oncology and Hematology, University of Manitoba

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Risk of Adverse Pathological Features for Intermediate Risk Prostate Cancer: Clinical Implications for Definitive Radiation Therapy

PONE-D-21-03241R1

Dear Dr. Zhang,

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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Kind regards,

Qinghui Zhang

Academic 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

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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

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

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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

**********

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: All changes were made, as requested. The paper is well-written and supports the growing literature that supports the routine use of mpMRI in the workup and treatment for prostate cancer.

Reviewer #2: I feel that the authors have written a good manuscript and that the paper is acceptable for publication.*

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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: No

Reviewer #2: No