Gender disparities in bladder cancer: A population-based study on life expectancy and health spending in Asia

Yi Hong Li; Yen-Chuan Ou; Min Che Tung; Yi Sheng Lin; Ya Chu Yang; Ying Ming Chiu; Chao Yu Hsu

doi:10.1371/journal.pone.0323803

Peer Review History

Original SubmissionNovember 11, 2024
11 Nov 2024 Author Response https://doi.org/10.1371/journal.pone.0323803.r001
5 Jan 2025 Decision Letter - Mazyar Zahir, Editor PONE-D-24-48193Gender disparities in bladder cancer: A population-based study on life expectancy and health spending in AsiaPLOS ONE Dear Dr. Ou, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Feb 19 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access. [Note: HTML markup is below. Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 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: No ****** 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 ****** 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: Dear Author Thank you for your retrospective cross-sectional study. 1: Was all the information you needed available in the patient file? 2: Why did you exclude all patients under the age of 30 from the study? Reviewer #2: Thank you for the opportunity to review this manuscript, and congratulations to the authors for conducting this study. The study from Taiwan, based on database exploration, compared life expectancy and medical expenditure between males and females, revealing interesting findings in their population. Here are some major issues worth addressing to improve the presentation of the work: 1. The reason for excluding individuals under 30 and over 90 years of age from the study should be added. 2. Some issues in the discussion need further elaboration. For example, the following finding requires more explanation: The CPLY for women peaked in the 30–59 age group ($8,308) and decreased with age, whereas for men, it peaked in the 80–89 age group ($5,758) and increased with age. 3. Why didn’t you divide males and females with 0IS in Table 3A? Throughout the manuscript, 0IS was not stratified by sex. 4. The primary driver of higher medical costs was introduced as hemodialysis. However, there is no information on how much of the costs were due to dialysis and the role of other expenditures. Providing this information would clarify it for the readers. 5. In the discussion section, you mentioned, “In our subgroup analysis, which examined the interplay between cancer stage and age, we observed a notable increase in aggressive stage diagnoses among female patients aged >70 years.” More clarification is suggested regarding the interplay between cancer stage and age for each sex in the results section. Additionally, here are some minor issues suggested for improvement: 1. In the results section of the abstract, it seems that “male” and “female” have been used incorrectly in this phrase: (3.17 [0.55] years for women vs. 7.14 [0.76] years for men). 2. Using MeSH terms is recommended for keywords. 3. Please recheck the numbers in the tables. For example, the percentages of the number of deaths in Table 3 seem incorrect. 4. In the discussion section, you mentioned, “CIS, also referred to as Tis in our study and categorized as stage 1, often…”. Doesn’t CIS categorize as stage 0? ****** 6. 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 ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0323803.r002
Revision 1
6 Feb 2025 Author Response Reviewer #1: Dear Author Thank you for your retrospective cross-sectional study. 1: Was all the information you needed available in the patient file? Answer: Thank you for your question. As noted in the "Limitation" section of the manuscript, certain factors—such as smoking habits, occupational exposure to chemicals, socioeconomic status, and insurance status—could not be directly obtained due to the inherent constraints of retrospective studies and database-based research. Additionally, self-paid medications and caregiving expenses, which are not covered by Taiwan’s National Health Insurance, could not be included in the analysis. While these limitations exist, we mitigated potential biases by matching our study population with the general population based on age, sex, and year of diagnosis. This limitation has been explicitly discussed in the manuscript to provide transparency regarding the scope and boundaries of our findings (page 29-30, line 459 to 477 in tracked changes file; page 28-29, line 445 to 463 in without tracked changes file). We also added an explanation in the text that such results might overlook the actual economic burden that patients and their families have to bear. 2: Why did you exclude all patients under the age of 30 from the study? Answer: Thank you for your comment. Patients aged <30 years was excluded for the following reasons: Patients aged 18–30 years were excluded because the number of cases in this age group was fewer than 100, making statistical stratification unreliable and limiting the potential for meaningful subgroup analysis. This exclusion was necessary to ensure the scientific rigor and interpretability of the study findings. This explanation has been added to the "Materials and Methods" section of the manuscript (page 7, line 104 to 110 in tracked changes file; page 7, line 103 to 109 in without tracked changes file). Reviewer #2: Thank you for the opportunity to review this manuscript, and congratulations to the authors for conducting this study. The study from Taiwan, based on database exploration, compared life expectancy and medical expenditure between males and females, revealing interesting findings in their population. Here are some major issues worth addressing to improve the presentation of the work: 1. The reason for excluding individuals under 30 and over 90 years of age from the study should be added. Answer: Thank you for your comment. Patients aged <30 years or >90 years were excluded for the following reasons: Patients aged 18–30 years were excluded because the number of cases in this age group was fewer than 100, making statistical stratification unreliable and limiting the potential for meaningful subgroup analysis. Patients aged >90 years were excluded due to shorter average life expectancy relative to the Taiwanese population(76.94 years for men and 83.74 years for women). These exclusions were necessary to ensure the scientific rigor and interpretability of the study findings. This explanation has been added to the "Materials and Methods" section of the manuscript (page 7, line 104 to 110 in tracked changes file; page 7, line 103 to 109 in without tracked changes file). 2. Some issues in the discussion need further elaboration. For example, the following finding requires more explanation: The CPLY for women peaked in the 30–59 age group ($8,308) and decreased with age, whereas for men, it peaked in the 80–89 age group ($5,758) and increased with age. Answer: Thank you for your insightful comments. After re-examining the data, we found that dialysis significantly contributes to total medical costs. In males, CPLY increases with age, which aligns with trends observed in previous studies indicating that healthcare needs and related complications tend to accumulate in older age groups. In contrast, the CPLY trend in females follows an inverse pattern compared to males. Our analysis revealed that the highest proportion of dialysis costs relative to total expenditures is observed in the 30–59 age group, accounting for 49.98% of the total. Notably, while the total hemodialysis costs for male patients amount to 27.62 million USD, female patients incur a significantly higher total of 43.52 million USD. Since our dialysis costs are based on 'known' expenses during the current tracking period, whereas CPLY estimates future costs based on these data, the 30-59 age group—having the most documented dialysis cases—contributes to the highest projected costs. This trend aligns with the observed cost patterns across the population. The gender disparity observed in dialysis costs underscores the importance of considering both the long-term financial burden of dialysis and the population's age structure when interpreting cost patterns. We have revised the results and discussion sections to reflect this additional context and appreciate the opportunity to clarify these points (page 16-17 , line 231 to 245 and revised Table 4 in tracked changes file; page 16 to 17, line 230 to 247 and revised Table 4 in without tracked changes file). 3. Why didn’t you divide males and females with 0IS in Table 3A? Throughout the manuscript, 0IS was not stratified by sex. Answer: Thank you for this observation. We did not stratify stage 0IS by sex in Table 3A because the female sample size (n=193) was relatively small compared to female in other stage. To ensure statistical reliability and avoid potential bias due to sample size imbalance, we combined both genders for analysis. Additionally, in the revised manuscript, we have clarified this point (page 13, line 192 to 197 in tracked changes file; page 13, line 191 to 195 in without tracked changes file). This approach allowed us to provide more robust and interpretable results while accounting for significant differences between groups.. This approach also highlights the notably higher mortality and CPLY observed in this subgroup, which we believe underscores the significance of this finding regardless of sex. 4. The primary driver of higher medical costs was introduced as hemodialysis. However, there is no information on how much of the costs were due to dialysis and the role of other expenditures. Providing this information would clarify it for the readers. Answer: Thank you for your insightful comment. We appreciate the opportunity to clarify the composition of medical expenditures, particularly the contribution of dialysis costs relative to other components. During the follow-up period, the distribution of medical expenses varied between males and females. In females, the cost composition was as follows: medications (14.9%), laboratory tests and imaging studies (34.1%), dialysis (39.7%), and medical consumables (4.4%). In contrast, the corresponding distribution in males was medications (19.2%), laboratory tests and imaging studies (52.0%), dialysis (16.1%), and medical consumables (4.4%) (page 9, line 137 to 143 in tracked changes file; page 9, line 136 to 142 in without tracked changes file). These findings highlight that dialysis accounted for a substantially larger proportion of total medical costs in females compared to males. This gender disparity suggests that differences in dialysis utilization may be a key factor influencing overall healthcare expenditures. We have incorporated these details into the revised manuscript to improve clarity and address this concern. 5. In the discussion section, you mentioned, “In our subgroup analysis, which examined the interplay between cancer stage and age, we observed a notable increase in aggressive stage diagnoses among female patients aged >70 years.” More clarification is suggested regarding the interplay between cancer stage and age for each sex in the results section. Answer: Thank you for your insightful comment. To address your concern, we have added further clarification in the results section to elaborate on the interplay between cancer stage and age for each sex. Specifically, we have highlighted the trends observed in our subgroup analysis, where a notable increase in the proportion of aggressive stage diagnoses (MIBC) was evident among female patients aged >70 years. Additionally, we have included a new Fig S3. to visually illustrate the trends in NMIBC, MIBC, and unknown stage distributions across different age groups for both sexes. This figure complements the text and provides a clear comparison of how cancer stage proportions change with age for males and females(page 14-15, line 211 to 214 in tracked changes file; page 14, line 210 to 213 and new Fig S3 in without tracked changes file). Additionally, here are some minor issues suggested for improvement: 1. In the results section of the abstract, it seems that “male” and “female” have been used incorrectly in this phrase: (3.17 [0.55] years for women vs. 7.14 [0.76] years for men). Answer: We acknowledge that there was an error in the labeling of the data for men and women. This misprint has been corrected in the revised manuscript 2. Using MeSH terms is recommended for keywords. Answer: We have updated the keywords to use appropriate MeSH terms as recommended. 3. Please recheck the numbers in the tables. For example, the percentages of the number of deaths in Table 3 seem incorrect. Answer: We have re‐calculated the percentages in Table 3 and confirmed that the values are correct. No changes were necessary based on our recalculations. 4. In the discussion section, you mentioned, “CIS, also referred to as Tis in our study and categorized as stage 1, often…”. Doesn’t CIS categorize as stage 0? Answer: We agree that CIS (Carcinoma In Situ) should be categorized as stage 0 rather than stage 1. This misprint has been corrected in the revised version. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0323803.r003
25 Feb 2025 Decision Letter - Mazyar Zahir, Editor PONE-D-24-48193R1Gender disparities in bladder cancer: A population-based study on life expectancy and health spending in AsiaPLOS ONE Dear Dr. Ou, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Apr 11 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Mazyar Zahir Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] 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: (No Response) Reviewer #3: (No Response) ******** 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: No Reviewer #2: (No Response) Reviewer #3: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: (No Response) Reviewer #3: (No Response) ****** 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: (No Response) Reviewer #3: (No Response) ****** 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: (No Response) Reviewer #3: (No Response) ****** 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: Dear Author Thank you for your revision . The items requested by me from the authors have been answered correctly and completely. Reviewer #2: The authors have properly addressed the comments, except for one. The death percentages in Table 2 appear to be incorrect. For instance, the percentage of deaths for low-grade females is listed as 159%. Other percentages in this table also seem incorrect, such as 1238 out of 6032 being reported as 74.98%. Please re-check the numbers in this table. Reviewer #3: - While the study uses advanced statistical techniques, it does not report p-values for the individual components and comparisons within the semiparametric method. Calculating a single p-value for the entire extrapolation process is challenging due to the complexity and multi-step nature of the method. However, it is recommended to report p-values for individual components, such as the comparison of survival rates and covariates using Cox proportional hazards models, to provide a clearer understanding of the statistical significance of the findings. - The method assumes homogeneity in the patient data concerning the variables incorporated within the model. Variability in treatment, access to healthcare, and other patient-specific factors may not be comprehensively considered and ought to be recognized as a limitation. - Extending the survival curve month by month involves extrapolating beyond the observed data, introducing uncertainties. This approach assumes that the trends observed in the initial months will continue, which might not always be the case. Including sensitivity analyses or validating the model with external data could strengthen the findings. - The reference group created using the Monte Carlo method based on life tables may not fully capture all variables affecting the general population's survival, such as comorbidities or socio-economic factors. This could lead to biased comparisons and should be discussed as a potential limitation. ****** 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 Reviewer #3: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0323803.r004
Revision 2
17 Mar 2025 Author Response Reviewer #1: Dear Author Thank you for your revision. The items requested by me from the authors have been answered correctly and completely. Answer: We sincerely appreciate your time and effort in reviewing our manuscript. We are grateful for your positive feedback and for acknowledging that we have adequately addressed your previous comments. As per your assessment, no additional revisions were required. Nonetheless, we have carefully re-reviewed the entire manuscript to ensure clarity, accuracy, and completeness, and we have made further refinements based on feedback from the other reviewers to enhance the overall quality of our work. Thank you again for your constructive review and support. Reviewer #2: The authors have properly addressed the comments, except for one. The death percentages in Table 2 appear to be incorrect. For instance, the percentage of deaths for low-grade females is listed as 159%. Other percentages in this table also seem incorrect, such as 1238 out of 6032 being reported as 74.98%. Please re-check the numbers in this table. Answer: We appreciate your careful review and for highlighting the discrepancies in Table 2. Upon re-examining our calculations, we discovered that errors arose from a misalignment in data extraction and an incorrect denominator for percentage calculations. We have thoroughly revised Table 2 (pages 12–13, revised Table 2) so that all reported values accurately reflect the proportion of deaths in each cohort. The corrected percentages now fall within expected ranges. Additionally, we reviewed all other tables and data sources to ensure consistency and accuracy throughout the manuscript. Thank you again for your constructive feedback, which has significantly improved the precision of our study. Reviewer #3: 1. While the study uses advanced statistical techniques, it does not report p-values for the individual components and comparisons within the semiparametric method. Calculating a single p-value for the entire extrapolation process is challenging due to the complexity and multi-step nature of the method. However, it is recommended to report p-values for individual components, such as the comparison of survival rates and covariates using Cox proportional hazards models, to provide a clearer understanding of the statistical significance of the findings. Answer: Thank you for your valuable feedback. In response, we have performed a multivariable Cox regression analysis including sex, age, pathological grade, and cancer stage (pages 8, lines 119–123). This analysis provides hazard ratios with 95% confidence intervals and p-values for each variable—for example, male sex is associated with a lower risk of death (HR 0.90, 95% CI 0.87–0.94, p < 0.01), while increasing age, high-grade tumors, and advanced-stage disease significantly elevate mortality risk (all p < 0.01). These results are detailed in the newly added Supplement Table S5 and summarized in the Results section (pages 16, lines 226–232, and new S2 Table). We believe this additional analysis enhances the statistical rigor and clarity of our findings. 2. The method assumes homogeneity in the patient data concerning the variables incorporated within the model. Variability in treatment, access to healthcare, and other patient-specific factors may not be comprehensively considered and ought to be recognized as a limitation. Answer: Thank you for this important comment. We acknowledge that our model assumes patient homogeneity for the included variables. In reality, variations in treatment, healthcare access, and other patient-specific factors may introduce residual confounding. We have revised the Limitations section to include the following statement (page 29, lines 458–460): "Moreover, our model assumes patient homogeneity for the included variables. In reality, variations in treatment, healthcare access, and other factors may introduce residual confounding." We believe this revision clearly recognizes the inherent heterogeneity in the patient population and enhances the transparency of our study. 3. Extending the survival curve month by month involves extrapolating beyond the observed data, introducing uncertainties. This approach assumes that the trends observed in the initial months will continue, which might not always be the case. Including sensitivity analyses or validating the model with external data could strengthen the findings. Answer: Thank you for your insightful comment. In response, we have inserted a sentence in the Methods section (page 8, lines 117–119; page 16, lines 221–226) describing a sensitivity analysis in which we compared life expectancy estimates extrapolated from the first 6 years of follow-up with 12-year Kaplan–Meier estimates (new Supplement S1 Table). The analysis revealed minimal relative bias, thereby supporting the robustness of our extrapolation approach despite inherent uncertainties. We hope this revision adequately addresses your concern. 4. The reference group created using the Monte Carlo method based on life tables may not fully capture all variables affecting the general population's survival, such as comorbidities or socio-economic factors. This could lead to biased comparisons and should be discussed as a potential limitation. Answer: Thank you for your valuable comment regarding our reference group. We recognize that using a Monte Carlo simulation based on life tables may not capture key factors—such as comorbidities and socioeconomic status—that affect the general population’s survival, potentially biasing comparisons. In response, we have revised the Limitations section (page 29, lines 457–458) to include the following statement: "Additionally, the Monte Carlo-based reference group may not capture key factors (e.g., comorbidities, socioeconomic status), potentially biasing comparisons." We believe this addition enhances the transparency of our study by clearly acknowledging this limitation. Attachments Attachment Submitted filename: Reviewer response.docx https://doi.org/10.1371/journal.pone.0323803.r005
15 Apr 2025 Decision Letter - Mazyar Zahir, Editor <p>Gender disparities in bladder cancer: A population-based study on life expectancy and health spending in Asia PONE-D-24-48193R2 Dear Dr. Ou, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. 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, Mazyar Zahir, MD 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 #2: All comments have been addressed Reviewer #3: All comments have been addressed ******** 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 #2: (No Response) Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: (No Response) Reviewer #3: 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 #2: (No Response) Reviewer #3: (No Response) ****** 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 #2: (No Response) Reviewer #3: (No Response) ****** 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 #2: (No Response) Reviewer #3: The items I previously requested from the authors have been addressed in a timely manner. I appreciate their responsiveness and the clarity of their answers. ****** 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 #2: No Reviewer #3: Yes: Nasrin Borumandnia ******** https://doi.org/10.1371/journal.pone.0323803.r006
Formally Accepted
Acceptance Letter - Mazyar Zahir, Editor PONE-D-24-48193R2 PLOS ONE Dear Dr. Ou, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Mazyar Zahir Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0323803.r007

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PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

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