Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors present a prospective study evaluating oncological outcomes following the omission of second transurethral resection (reTURBT) in patients with high-risk T1 non-muscle invasive bladder cancer, an approach necessitated by limited healthcare resources during the COVID-19 pandemic. The topic is clinically significant and timely, addressing a key aspect of bladder cancer management with potential implications for future practice.

Overall, the manuscript is well-organized and clearly written. However, several points warrant clarification and further discussion 

A key strength lies in the study’s prospective design and the use of clearly defined inclusion and exclusion criteria. Nevertheless, the following concerns should be addressed:

First, the relatively small sample size (43 patients) limits the statistical power and generalizability of the findings. The authors should more explicitly acknowledge this limitation in the discussion section and advise caution in interpreting the results. Validation through larger, ideally multicenter, studies would be necessary.

Second, although no statistically significant difference in recurrence-free survival was found between groups, the higher recurrence rate observed in the reTURBT group warrants deeper exploration. This finding is unexpected and contrasts with existing literature; the authors should offer possible explanations and contextualize the result within prior evidence.

Third, the criteria for omitting reTURBT during the pandemic—specifically, complete resection with confirmed detrusor muscle—were quite selective. The manuscript would benefit from a more in-depth analysis of potential selection bias. In particular, the possibility that these resections were performed with heightened diligence due to increased clinical vigilance during the pandemic should be acknowledged as a factor that could influence outcomes.

Fourth, the significantly longer median interval before BCG instillation in the reTURBT group (139 vs. 60 days) may have confounded the results. This disparity should be addressed more fully, as earlier BCG administration in the non-reTURBT group might have contributed to better outcomes.

Lastly, while the authors mention emerging diagnostic modalities such as narrow-band imaging and photodynamic diagnosis, these were not employed in the present study. Including a clearer discussion of how such technologies might be integrated into future studies or clinical workflows would help underscore the relevance and potential evolution of diagnostic strategies in this context.

In summary, the study contributes valuable preliminary insights into a resource-adaptive approach to high-risk T1 bladder cancer. Addressing the above limitations more explicitly will enhance the manuscript’s scientific rigor and practical value.

Recommendation:
 recommended to improve clarity and contextual depth 

Author Response

We would like to thank for thorough evaluation of our manuscript. We greatly appreciate the constructive comments and insightful suggestions, which have significantly helped us to improve the quality and clarity of the manuscript. We have carefully addressed each point raised and incorporated the necessary changes.

Comment 1: First, the relatively small sample size (43 patients) limits the statistical power and generalizability of the findings. The authors should more explicitly acknowledge this limitation in the discussion section and advise caution in interpreting the results. Validation through larger, ideally multicenter, studies would be necessary.

Response 1: We acknowledge that the limited sample size renders the study underpowered to detect statistically significant differences in recurrence or progression. We have revised the abstract, discussion, and conclusion to explicitly reflect this limitation and to caution against overinterpreting the absence of statistically significant findings.

Comment 2: Second, although no statistically significant difference in recurrence-free survival was found between groups, the higher recurrence rate observed in the reTURBT group warrants deeper exploration. This finding is unexpected and contrasts with existing literature; the authors should offer possible explanations and contextualize the result within prior evidence.

Response 2: We acknowledge that the higher recurrence rate observed in the reTURBT group, despite not reaching statistical significance, is counterintuitive and contrasts with existing literature. We have addressed this issue in the revised discussion, offering potential explanations such as selection bias, differences in tumour biology, and the timing of adjuvant therapy. We have also contextualized our findings in light of prior meta-analyses and prospective studies.

Comment 3: Third, the criteria for omitting reTURBT during the pandemic—specifically, complete resection with confirmed detrusor muscle—were quite selective. The manuscript would benefit from a more in-depth analysis of potential selection bias. In particular, the possibility that these resections were performed with heightened diligence due to increased clinical vigilance during the pandemic should be acknowledged as a factor that could influence outcomes.

Response 3: We agree that the criteria for omitting reTURBT were inherently selective and that the pandemic context may have led to heightened surgical diligence. We have expanded our discussion on potential selection bias to acknowledge that patients selected for reTURBT omission may have benefited from more meticulous resections and closer pre-treatment evaluation, which could have favorably influenced their outcomes.

Comment 4: Fourth, the significantly longer median interval before BCG instillation in the reTURBT group (139 vs. 60 days) may have confounded the results. This disparity should be addressed more fully, as earlier BCG administration in the non-reTURBT group might have contributed to better outcomes.

Response $: We agree that the time to BCG instillation is a relevant factor. However, we would like to clarify that in our study the time interval to BCG was calculated from the initial TURBT in both groups. Consequently, the longer interval observed in the reTURBT group reflects the additional time required to perform the second resection and allow for adequate postoperative recovery before initiating intravesical therapy. While this delay is inherent to the reTURBT protocol, it does not represent a protocol deviation or treatment delay per se. We have clarified this point in the Methods and expanded on its possible impact in the Discussion.

Comment 5: Lastly, while the authors mention emerging diagnostic modalities such as narrow-band imaging and photodynamic diagnosis, these were not employed in the present study. Including a clearer discussion of how such technologies might be integrated into future studies or clinical workflows would help underscore the relevance and potential evolution of diagnostic strategies in this context.

Responde 5: We agree that the integration of emerging diagnostic modalities such as narrow-band imaging (NBI) and photodynamic diagnosis (PDD) is highly relevant to the future management of NMIBC. Although these technologies were not available in our institution at the time of the study, we have expanded the discussion to reflect their potential role in improving tumour visualization, guiding resection quality, and possibly reducing reliance on routine reTURBT in well-selected patients.

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript explores the oncological outcomes of omitting a second transurethral resection of bladder tumor (reTURBT) in a real world setting (COVID-19 pandemic impact).

 

amendments: 

 

• In the introduction (lines 33–37), the reference to the EAU Guidelines regarding indications for reTURBT is somewhat vague. I recommend being more precise and aligned with the actual guideline wording.
• The introduction is somewhat vague and redundant, especially regarding the role of the COVID-19 pandemic. While the impact of the pandemic on surgical protocols is relevant, the current text repeats this concept multiple times and does not provide a concise, structured rationale
• The division into reTURBT and non-reTURBT groups based on COVID-related constraints introduces a potential selection bias, as group assignment was not randomized. This should be more clearly acknowledged as a limitation of the study design.
• The discussion does a good job citing relevant meta-analyses, but the manuscript would benefit from better integration of newer studies (e.g., risk stratification via molecular biomarkers - please cite DOI: 10.1016/j.urolonc.2025.01.007)
• With only 43 patients (17 reTURBT vs. 26 no reTURBT), the study is underpowered to detect differences in recurrence or progression. The absence of statistically significant findings should be interpreted cautiously, and this limitation must be more explicitly addressed in the abstract, discussion, and conclusion.

Comments on the Quality of English Language

none

Author Response

Thank you for your thorough evaluation of our manuscript.

Comments 1: In the introduction (lines 33–37), the reference to the EAU Guidelines regarding indications for reTURBT is somewhat vague. I recommend being more precise and aligned with the actual guideline wording.

Response 1: We have revised the paragraph in the Introduction (lines 33–37) to reflect a more accurate and faithful representation of the EAU Guidelines 2025. We now specifically describe the three main indications for reTURBT as outlined by the guidelines: detection of residual disease, accurate pathological staging, and retrieval of missing clinical information. We also cite the high rates of residual tumour and under-staging reported in the guidelines to support this rationale.

Comments 2: The introduction is somewhat vague and redundant, especially regarding the role of the COVID-19 pandemic. While the impact of the pandemic on surgical protocols is relevant, the current text repeats this concept multiple times and does not provide a concise, structured rationale

Response 2: We agree that the role of the COVID-19 pandemic in our introduction was somewhat repetitive. To improve clarity and flow, we have streamlined the text to provide a concise and structured rationale for the study, limiting redundancy while retaining the necessary contextual background about the protocol change during the pandemic.

Comments 3: The division into reTURBT and non-reTURBT groups based on COVID-related constraints introduces a potential selection bias, as group assignment was not randomized. This should be more clearly acknowledged as a limitation of the study design.

Response 3: We have explicitly acknowledged this limitation in the revised discussion section and clarified its possible impact on the interpretation of our results.

Comments 4: The discussion does a good job citing relevant meta-analyses, but the manuscript would benefit from better integration of newer studies (e.g., risk stratification via molecular biomarkers - please cite DOI: 10.1016/j.urolonc.2025.01.007)

Response 4: In the revised discussion, we have integrated the recent study by Russo et al. (DOI: 10.1016/j.urolonc.2025.01.007), which explores the prognostic role of the Systemic Inflammation Response Index (SIRI) in bladder cancer patients. This allows us to contextualize our findings within the current trend toward biomarker-driven risk stratification and personalized treatment strategies.

Comments 5: With only 43 patients (17 reTURBT vs. 26 no reTURBT), the study is underpowered to detect differences in recurrence or progression. The absence of statistically significant findings should be interpreted cautiously, and this limitation must be more explicitly addressed in the abstract, discussion, and conclusion.

Response 5: Thank you for this important observation. We acknowledge that the limited sample size (43 patients) renders the study underpowered to detect statistically significant differences in recurrence or progression. We have revised the abstract, discussion, and conclusion to explicitly reflect this limitation and to caution against overinterpreting the absence of statistically significant findings.

Reviewer 3 Report

Comments and Suggestions for Authors

This is a timely and clinically relevant study addressing whether omitting reTURBT in carefully selected high-risk T1 NMIBC patients compromises oncological outcomes. The COVID-19 pandemic offers a unique context in which protocol deviations occurred naturally

Please consider following considerations:

1- The Materials and Methods section would benefit from greater clarity regarding the criteria used to define “complete resection” and the presence of detrusor muscle. Were these confirmed by pathology or operative reports? Standardizing these definitions is key for reproducibility.

2 - While the results are intriguing, the study’s exploratory nature should be emphasized more clearly, particularly in the title and conclusions. A reframing as a hypothesis-generating pilot study would be more appropriate. 

3 - The introduction currently includes elements of discussion, particularly when referring to meta-analyses and outcomes of reTURBT. I recommend avoiding an early mini-discussion and instead focusing the introduction on outlining the clinical background, guideline recommendations, and the specific rationale for the present study + intro please include: doi: 10.23736/S2724-6051.24.05876-2. + avoid repetitions  

Comments on the Quality of English Language

it is ok

Author Response

Thank you very much for yur comments that made better our manuscript. 

Comments 1: The Materials and Methods section would benefit from greater clarity regarding the criteria used to define “complete resection” and the presence of detrusor muscle. Were these confirmed by pathology or operative reports? Standardizing these definitions is key for reproducibility.

Response 1: The definition of complete resection was taken from the operative report, which should contain, according to the EAU guidelines, if the resection was visually complete and the visualisation of muscle at the resection base.

Comments 2:  While the results are intriguing, the study’s exploratory nature should be emphasized more clearly, particularly in the title and conclusions. A reframing as a hypothesis-generating pilot study would be more appropriate. 

Response 2: We agree that the study’s exploratory nature should be more clearly emphasized. In response, we have revised the title and conclusions to better reflect that this is a hypothesis-generating pilot study. These changes help to properly frame the scope and limitations of our findings.

Comments 3: The introduction currently includes elements of discussion, particularly when referring to meta-analyses and outcomes of reTURBT. I recommend avoiding an early mini-discussion and instead focusing the introduction on outlining the clinical background, guideline recommendations, and the specific rationale for the present study + intro please include: doi: 10.23736/S2724-6051.24.05876-2. + avoid repetitions 

Responde 3: We have revised the section to focus more clearly on the clinical background, guideline recommendations, and the specific rationale for our study. Redundant elements have been removed to improve clarity and flow. The citation has also been added as requested.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript has improved significantly

Comments on the Quality of English Language

none

Author Response

Thank you for your comments. 

Reviewer 3 Report

Comments and Suggestions for Authors

We kindly suggest reviewing and correcting the enumeration of citations throughout the manuscript

consider adding in the discussion the following   DOI: 10.3390/medicina59122063

This study aligns with your line of reasoning and could help strengthen the general impact and contextual relevance of your findings.

Comments on the Quality of English Language

minor typos  

Author Response

Thank you for your comments. 

Comments 1: We kindly suggest reviewing and correcting the enumeration of citations throughout the manuscript

Responds 1: We have carefully reviewed the entire manuscript and corrected the enumeration and formatting of references to ensure consistency and adherence to the journal’s guidelines. 

Comments 2: Consider adding in the discussion the following   DOI: 10.3390/medicina59122063

Responds 2: We have incorporated the study suggested by the reviewer (Russo et al., Medicina 2023; DOI: 10.3390/medicina59122063) into the Discussion section.