Reviewer’s report
Title: 
Determining the survival benefit of postoperative radiotherapy in patients
with pT1-3N1M0 rectal cancer undergoing total mesorectal excision: a
retrospective analysis
Version: 
0 
Date: 
31 Jul 2022
Reviewer's report:
The manuscript by Chen and colleagues describes a SEER based retrospective
analysis of the role of postoperative chemotherapy with or without radiotherapy
in patients with "low-risk" rectal cancer who had not received preoperative
treatment. The rational to conduct this study is the fact that the NCCN guidelines
recommend postoperative chemoradiotherapy in stage III rectal cancer patients
without preoperative therapy in the era of improved TME surgery and standard
preoperative (chemo)radiotherapy in intermediate/high risk patients.
Given the disbalance in the target population, the investigators performed a
propensity score matching allowing to study their primary endpoint of cancer-
specific survival (CSS). 
The main finding from the total matched cohort of 842 patients, was that only in
the subgroups of patients with 3 or more tumor positive lymph nodes and those
with tumors larger than 5 cm, a statistically significant improved CSS can be
expected.
Based on their findings, the authors suggest to take these two adverse prognostic
factors into account in the guidelines to support the decision to treat
postoperatively. 
The question addressed in this study is clinically relevant, however, there are
several major issues that do not justify its acceptance for publication:
1. First of all, the English is very poor, making the article difficult to read. This
starts with the title that is not a proper English sentence. Many more examples
follow. The paper should be checked and rewritten.
2. Current guidelines are based on the highest level of evidence from randomized
trials. Although it can be argued that RWD are important as well, the results
from the current analysis cannot be considered to make treatment choices in
clinical practice. Many relevant factors such as information on CRM, EMI and
MRI (re)staging are lacking. Therefore, the results do not add sufficient new
information to the current knowledge and are therefore of limited value to the
scientific community.
3. The authors indicate pT1-3N1M0 as "low-risk", yet these stages also include
intermediate risk disease that should receive preoperative (chemo)radiotherapy
according to current guidelines. In addition, these stages are not in agreement
with the locally advanced stages mentioned in the NCCN guidelines. It is not
clear why the authors limited their target cohort by making this selection.
4. Figures 3A, 3B, 3C, 3D, 4A, 4B, 6A, 6B, 6C, 6D, 7A, 7B, 7C are redundant
and should be presented in a table or moved to the supplementary part.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Determining the survival benefit of postoperative radiotherapy in patients
with pT1-3N1M0 rectal cancer undergoing total mesorectal excision: a
retrospective analysis
Version: 
0 
Date: 
31 Jul 2022
Reviewer's report:
The manuscript by Chen and colleagues describes a SEER based retrospective
analysis of the role of postoperative chemotherapy with or without radiotherapy
in patients with "low-risk" rectal cancer who had not received preoperative
treatment. The rational to conduct this study is the fact that the NCCN guidelines
recommend postoperative chemoradiotherapy in stage III rectal cancer patients
without preoperative therapy in the era of improved TME surgery and standard
preoperative (chemo)radiotherapy in intermediate/high risk patients.
Given the disbalance in the target population, the investigators performed a
propensity score matching allowing to study their primary endpoint of cancer-
specific survival (CSS). 
The main finding from the total matched cohort of 842 patients, was that only in
the subgroups of patients with 3 or more tumor positive lymph nodes and those
with tumors larger than 5 cm, a statistically significant improved CSS can be
expected.
Based on their findings, the authors suggest to take these two adverse prognostic
factors into account in the guidelines to support the decision to treat
postoperatively. 
The question addressed in this study is clinically relevant, however, there are
several major issues that do not justify its acceptance for publication:
1. First of all, the English is very poor, making the article difficult to read. This
starts with the title that is not a proper English sentence. Many more examples
follow. The paper should be checked and rewritten.
2. Current guidelines are based on the highest level of evidence from randomized
trials. Although it can be argued that RWD are important as well, the results
from the current analysis cannot be considered to make treatment choices in
clinical practice. Many relevant factors such as information on CRM, EMI and
MRI (re)staging are lacking. Therefore, the results do not add sufficient new
information to the current knowledge and are therefore of limited value to the
scientific community.
3. The authors indicate pT1-3N1M0 as "low-risk", yet these stages also include
intermediate risk disease that should receive preoperative (chemo)radiotherapy
according to current guidelines. In addition, these stages are not in agreement
with the locally advanced stages mentioned in the NCCN guidelines. It is not
clear why the authors limited their target cohort by making this selection.
4. Figures 3A, 3B, 3C, 3D, 4A, 4B, 6A, 6B, 6C, 6D, 7A, 7B, 7C are redundant
and should be presented in a table or moved to the supplementary part.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Determining the survival benefit of postoperative radiotherapy in patients
with pT1-3N1M0 rectal cancer undergoing total mesorectal excision: a
retrospective analysis
Version: 
0 
Date: 
31 Jul 2022
Reviewer's report:
The manuscript by Chen and colleagues describes a SEER based retrospective
analysis of the role of postoperative chemotherapy with or without radiotherapy
in patients with "low-risk" rectal cancer who had not received preoperative
treatment. The rational to conduct this study is the fact that the NCCN guidelines
recommend postoperative chemoradiotherapy in stage III rectal cancer patients
without preoperative therapy in the era of improved TME surgery and standard
preoperative (chemo)radiotherapy in intermediate/high risk patients.
Given the disbalance in the target population, the investigators performed a
propensity score matching allowing to study their primary endpoint of cancer-
specific survival (CSS). 
The main finding from the total matched cohort of 842 patients, was that only in
the subgroups of patients with 3 or more tumor positive lymph nodes and those
with tumors larger than 5 cm, a statistically significant improved CSS can be
expected.
Based on their findings, the authors suggest to take these two adverse prognostic
factors into account in the guidelines to support the decision to treat
postoperatively. 
The question addressed in this study is clinically relevant, however, there are
several major issues that do not justify its acceptance for publication:
1. First of all, the English is very poor, making the article difficult to read. This
starts with the title that is not a proper English sentence. Many more examples
follow. The paper should be checked and rewritten.
2. Current guidelines are based on the highest level of evidence from randomized
trials. Although it can be argued that RWD are important as well, the results
from the current analysis cannot be considered to make treatment choices in
clinical practice. Many relevant factors such as information on CRM, EMI and
MRI (re)staging are lacking. Therefore, the results do not add sufficient new
information to the current knowledge and are therefore of limited value to the
scientific community.
3. The authors indicate pT1-3N1M0 as "low-risk", yet these stages also include
intermediate risk disease that should receive preoperative (chemo)radiotherapy
according to current guidelines. In addition, these stages are not in agreement
with the locally advanced stages mentioned in the NCCN guidelines. It is not
clear why the authors limited their target cohort by making this selection.
4. Figures 3A, 3B, 3C, 3D, 4A, 4B, 6A, 6B, 6C, 6D, 7A, 7B, 7C are redundant
and should be presented in a table or moved to the supplementary part.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant