PONE-D-22-17365Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancerPLOS ONE

Dear Dr. Holmberg,

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PLOS ONE

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Additional Editor Comments:

Dear Prof. Holmberg,

We appreciate your submission to PLoS ONE. In addition to the reviewers’ comments, I would like to bring up a couple of points required your clarifications:

1. Firstly, I feel confused as regards the comparison cohort was matched on what variables exactly, as there were inconsistent statements in your paper --

(a). P. 5, lines 103-104, “Controls were matched for sex, year of birth and county of residence”.

(b). P. 7, lines 169-170, “… the comparison cohort, matched for age, sex and county. We adjusted the models for prognostic group, CCI and educational level but not for the matching factors”.

(c). P. 8, lines 178-179, “These analyses were adjusted for prognostic group, CCI, educational level and age”.

Based on the statistics in Table 1, I assume the matched variables were sex, age, and education.

2. Furthermore, concerning some 95% CI statistics:

(a). P. 12, lines 240-241, “… however with lower unadjusted HRs than for overall mortality varying from 1.04 (95% CI 1.00-1.07)”.

(b). P. 12, line 232, “… the absolute difference at ten years was 1.4% (95% CI 0.7%-2.1%)”.

If the confidence interval crosses 1, then it implies that the HR is not statistically significant (i.e., there is no difference between arms of the study).

Kuo-Cherh Huang

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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: Yes

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: the authors reported their experience on Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer.

the research is well pconducted and well presented.

Anymway, I suggest some rivisions:

- please state the sample size calculation

- when possible, perform a flow chart on included/exluded patients

- were patients consecutive?

- in my opinion, it is better to evaluate the risk classification rather than the grade alone of bladder cancer

Reviewer #2: The Authors investigated the overall and disease-specific risk of death in patients with NMIBC

28 compared to a background population sample. The manuscript is well written, with a good statistical analysis and explore an interesting topic. My compliments to the Authors.

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Reviewer #1: No

Reviewer #2: Yes: Simone Sforza

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Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer

PONE-D-22-17365R1

Dear Dr. Holmberg,

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,

Kuo-Cherh Huang

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Prof. Holmberg,

Your rebuttal letter and re-submitted manuscript are much appreciated.  Both reviewers are positive regarding your responses.  Here, I have a remaining issue for your consideration, albeit I recommend the acceptance of your work.

One of my previous concerns was about the matched variables of your analysis as there were inconsistent statements in your paper -- (a). P. 5, lines 103-104, “Controls were matched for sex, year of birth and county of residence”.  (b). P. 7, lines 169-170, “… the comparison cohort, matched for age, sex and county. We adjusted the models for prognostic group, CCI and educational level but not for the matching factors”.  (c). P. 8, lines 178-179, “These analyses were adjusted for prognostic group, CCI, educational level and age”.  Due to the fact that frequency distributions were nearly identical between the two groups with respect to sex, age, and education in Table 1, so I would comment so at the time -- “Based on the statistics in Table 1, I assume the matched variables were sex, age, and education.”

In the rebuttal letter you had responded: “The matching between the NMIBC-patients and their comparison cohort was for sex, year of birth and county of residence. We thank you for indicating that we did not word this consistently and have now done so in the manuscript. The analyses mentioned under (c) above were not done on the matched dataset; they did not include the comparison cohort which we now have underlined more specifically in the manuscript. Thus, these analyses did not include matching, but adjustment for prognostic group, CCI, educational level and age.”

Firstly, I am not quite sure about what you meant -- “The analyses mentioned under (c) above were not done on the matched dataset; they did not include the comparison cohort [emphasis added] which we now have underlined more specifically in the manuscript.”  Secondly, in Table 1 the comparisons were carried out between the NMIBC cohort and the matched comparison cohort, if I am correct.  That’s why I assumed the matched variables were sex, age, and education, based on the statistics.  Indeed, in the revised manuscript you stated: “Table 1 shows the baseline characteristics of the patients in the NMIBC cohort and their 192,733 age-, sex- and county matched individuals in the comparison cohort.” (p. 9, lines 209-211).  It is clear that age is one of the matched variables.  Accordingly, the declaration seems to be problematic -- “Thus, these analyses did not include matching, but adjustment for prognostic group, CCI, educational level and age.”  Finally, I think “year of birth” and “age” would result in the same effect on your analysis, although you affirmed that the variable of year of birth was the matched variable, while age was not (that is, for the purpose of adjustment, rather -- “but adjustment for prognostic group, CCI, educational level and age”).  Then again, the argument is incompatible with the descriptor -- “age-, sex- and county-matched individuals in the comparison cohort”. 

Thank you.

Kuo-Cherh Huang

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

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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

**********

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

Reviewer #1: 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

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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

**********

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: the authors improved the quality of the paper "Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer" by following all the suggested revisions.

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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: Luca Di Gianfrancesco

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