Predictive Value of Inflammatory and Nutritional Indexes in the Pathology of Bladder Cancer Patients Treated with Radical Cystectomy

Round 1

Reviewer 1 Report

In the present manuscript entitled “Predictive value of inflammatory and nutritional indexes in the pathology of bladder cancer patients treated with radical cystectomy” the authors address an interesting topic which has relevance in Bladder cancer prognostication, reporting the correlation of inflammatory and nutritional indexes with histopathological characteristics and prognostic features of urothelial bladder carcinoma. They have successfully performed an in-depth statistical analysis of a sufficient cohort, in order to conclude in accurate results.

The manuscript is greatly written and the results support the working hypothesis and the general conclusions of the manuscript.

 

However, I have a major concern which significantly lowers the quality of the study and the overall merit of the manuscript. The illustration and presentation of the results is of utmost importance for a manuscript to be appealing to the reader and to deliver the conclusions.

 

The quality of the results’ illustration is clearly insufficient. The authors have generated only a number of tables to organize and present their results. Statistically significant results from tables 3-10 should be illustrated using barplots/boxplots/violinplots/forest plots or spearman plots depending on correlation of categorical/continuous variables. Also, table 10 is hardly readable.

Few other minor issues that the authors should address, in order to ameliorate their manuscript and publish their results are listed below:

1.     Material-Methods section. The authors should organize materials and methods section using subsections. E.g. Screening cohort and baseline characteristics, inflammatory and nutritional indexes calculation, Statistical analysis.

2.     Which statistical test was used for the generation of the p-values in Table 3?

3.     Which tests have you used to test the normal distribution of the data?

Author Response

Dear Reviewer,

Thank you very much for taking the time to review our manuscript and for providing constructive feedback.

We have addressed the comments and included changes/additional data, which have improved our manuscript. The response to the comments is below.

1. The quality of the results’ illustration is clearly insufficient. The authors have generated only a number of tables to organize and present their results. Statistically significant results from tables 3-10 should be illustrated using barplots/boxplots/violinplots/forest plots or spearman plots depending on correlation of categorical/continuous variables. Also, table 10 is hardly readable.

We thank the reviewer for this comment. We comply with the reviewer comment and we have created figures to graphically display statistically significant results from Tables 4 to 9. Given the relatively large number of data and tables in our Results section, your suggestion regarding where to place added Figures would be important to us. Namely, we are not sure if a large amount of data would be appropriate in the manuscript body, or we should perhaps present part of the results as supplementary material. Please find all figures that we have additionaly created in the separate file attached to this letter. 

2. Material-Methods section. The authors should organize materials and methods section using subsections. E.g. Screening cohort and baseline characteristics, inflammatory and nutritional indexes calculation, Statistical analysis.

We thank the reviewer for this comment. We have made changes and organized  Material-Methods section with using subsections to comply with the reviewer comments.

3. Which statistical test was used for the generation of the p-values in Table 3?

We thank the reviewer for this comment. Statistical test that was used for the generation of the p-values in Table 3 is Spearman's rank correlation, and we have added it in the Legend below the Table 3.

4. Which tests have you used to test the normal distribution of the data?

We thank the reviewer for this comment. To test the normal distribution of the data, we have used the Kolmogorov–Smirnov test and we have added it in the Statistical analysis subsection in Material and Methods section.

In the hope that you will respond positively to our corrections, we thank you in advance.

Sincerely,

Uros Babic

Author Response File: Author Response.docx

Reviewer 2 Report

A very interesting paper, however, it lacks a conclusion on how to apply these findings in clinical practice. In the analyzed group, there is a big group of patients with the disease at the MIBC stage (90%), and only 10% with NMIBC. Since these are to be potential markers of progression, the research should be carried out in accordance with the REMARK recommendations.

Author Response

Dear Reviewer,

Thank you very much for taking the time to review our manuscript and for providing constructive feedback.

We have addressed the comments and provide response below.

• A very interesting paper, however, it lacks a conclusion on how to apply these findings in clinical practice.

We thank the reviewer for this comment. Our study showed a multiple association of inflammatory and nutritional indexes with histopathological characteristics of urothelial bladder carcinoma. Morover, we found a predictive value of SIRI, dNLR and GNRI for the presence of lymphovascular invasion, positive surgical margins and the presence of lymph node metastases after radical cystectomy, respectively. Currently, it is not that simple to assess the clinical value and how to apply these findings in clinical practice. Considering that these inflammatory and nutritional indexes in patients with bladder cancer are easily accessable, it will be reasonable in further research to investigate them as potential biomarkers for better patient selection for radical surgical treatment and their influence on treatment outcome, eg. overall survival.

• In the analyzed group, there is a big group of patients with the disease at the MIBC stage (90%), and only 10% with NMIBC. 

We thank the reviewer for this comment. All patients in our study who underwent radical cystectomy based on preoperatively diagnosed and pathohistologically confirmed MIBC or high-risk NMIBC. However, after radical cystectomy, definitive pathological stage was obtained. According to literature data, the majority of patients who underwent radical cystectomy will have MIBC stage of disease. Our population of patients with MIBC stage (90%) after radical cystectomy is in line with literature data.

• Since these are to be potential markers of progression, the research should be carried out in accordance with the REMARK recommendations.

Our study aimed to examine the relationship between nutritional and inflammatory indexes and the pathohistological characteristics of bladder cancer. Given that further research is needed to show the correlation of the examined factors with prognosis in these patients, we believe that in our study the REMARK recommendations are not applicable.

In the hope that you will respond positively to our response, we thank you in advance.

Sincerely,

Uros Babic

 

Reviewer 3 Report

Prijovic et al. conducted an observational study that found multiple connections between inflammatory and nutritional factors and the histological features of urothelial bladder cancer. Additionally, they discovered that SIRI, dNLR, and GNRI can predict the likelihood of lymphovascular invasion, positive surgical margins, and lymph node metastases after radical cystectomy, respectively. Although it is an observational study, it is informative, it would have been nicer if more patients could be recruited.

Author Response

Dear Reviewer,

Thank you very much for taking the time to review our manuscript and for providing constructive feedback.

We have addressed the comments and provide response below.

1. Although it is an observational study, it is informative, it would have been nicer if more patients could be recruited.

We thank the reviewer for this comment. We agree that number of patients included in this retrospective observational study is relatively small, and we have addressed it as one of the limitations of our study.  First reason is that this is a single center study conducted in the most important center in our country with the largest number of radical cystectomies performed annualy. Second reason is a lack of quality electronic documentation for patients who were hospitalized before 2017. Therefore, the number of patents who were enroled in this study represent the number of all eligible patients with available quality electronic documentation who were surgicaly treated with radical cystectomy in the most important single center in Serbia during the period from from January 1, 2017. to December 31, 2021.

In the hope that you will respond positively to our response, we thank you in advance.

Sincerely,

Uros Babic

Round 2

Reviewer 1 Report

The authors have addressed most of my suggestions. However the quality of the figures presented is still very poor and not informatic. Only barplots can be generated from the results?

What are the variables in y axis of all of the figures generated?

Also, p-values should be indicated in the figures.

In my opinion figures are important for the better illustration of the results in the main text and should be included in the main revised manuscript.

Author Response

Dear Reviewer,

Thank you very much for taking the time to review our manuscript and for providing constructive feedback.

We have addressed the comments and included changes/additional data, which have improved our manuscript. The response to the comments is below.

1. However the quality of the figures presented is still very poor and not informatic. Only barplots can be generated from the results?

We thank the reviewer for this comment. In the revised manuscript, we presented part of our results graphically through barplots. Given the relatively large amount of results in the manuscript, we believe that additional graphical representation would make the manuscript more difficult to read.

2. What are the variables in y axis of all of the figures generated?

We thank the reviewer for this comment. Given that the y-axis of the figure presents the numerical values of the displayed indexes, and they do not have a measurement unit (e.g. NLR is the ratio of two absolute numbers of the same order of magnitude), only the observed numerical values are shown in the y-axis

3. Also, p-values should be indicated in the figures.

We thank the reviewer for this comment. We included p-values in the figures in revised manuscript.

4. In my opinion figures are important for the better illustration of the results in the main text and should be included in the main revised manuscript.

We thank the reviewer for this comment. We appreciate your opinion and suggestions, so we included figures in the main revised manuscript.

Given the relatively large number of tables and results presented in the manuscript, we decided not to present in the revised manuscript part of the results related to the association of inflammatory and nutritional parameters with the histopathological subtype of urothelial carcinoma. We believe that our manuscript does not lose the quality of the results, and in this way the more significant results that indicate the connection between the examined indexes and histopathological characteristics that are important for the prognosis of the disease will be better highlighted. Also, the last table with the results of the binary logistic regression becomes clearer.

In the hope that you will respond positively to our corrections, we thank you in advance.

Sincerely,

Uros Babic