Renal Decompression for Malignant Ureteric Obstruction: A Tertiary Hospital Cohort Analysis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a retrospective study evaluating the characteristics, survival outcomes, renal function outcomes, complications, and application of the PLACT prognostic score in patients with Malignant Ureteric Obstruction (MUO) treated at a tertiary urology unit in Australia between January 1, 2018, and December 31, 2023. The study focuses on patients who underwent urinary decompression via retrograde ureteric stent insertion or percutaneous nephrostomy, aiming to assess clinical challenges and validate the PLACT score in an Australian cohort. Here are my concerns:

 

1. The study does not evaluate the PLACT score’s clinical utility, particularly in the context of emergency interventions, which comprised 75% of cases. The score is intended to guide treatment decisions, but in emergencies, decompression may occur regardless of prognosis, limiting the score’s practical value. The authors should assess the score’s impact on clinical decision-making, possibly through a decision curve analysis or by evaluating its use in elective vs. emergency settings.

 

2. The validation process uses Kaplan-Meier curves and log-rank tests to compare survival across PLACT risk groups but does not report multivariate analyses to adjust for potential confounders (e.g., age, comorbidities, cancer stage, ECOG performance status). Factors like female sex, identified as associated with poorer survival, may reflect confounding rather than true prognostic effects.

 

3. The study does not report standard validation metrics such as discrimination (e.g., Harrell’s concordance probability or area under the receiver operating characteristic curve) or calibration (e.g., calibration plots or Hosmer-Lemeshow test). These metrics are essential to confirm that the PLACT score accurately distinguishes between risk groups and that predicted survival probabilities align with observed outcomes in the Australian cohort.

 

Author Response

Comment 1: The study does not evaluate the PLACT score’s clinical utility, particularly in the context of emergency interventions, which comprised 75% of cases. The score is intended to guide treatment decisions, but in emergencies, decompression may occur regardless of prognosis, limiting the score’s practical value. The authors should assess the score’s impact on clinical decision-making, possibly through a decision curve analysis or by evaluating its use in elective vs. emergency settings.

Response 1: Thank you for your comment. We agree that an analysis on its ability to impact clinical decision making could make this more powerful, and ideally it would be in a prospective setting. We have included in the results section, the median survival times for Emergency and Elective settings separated by PLaCT group. We hope this additional information will aid the readers when making clinical decision making which is very nuanced and sensitive in the emergency setting. Thank you for your comment. 

 

Comment 2: "The validation process uses Kaplan-Meier curves and log-rank tests to compare survival across PLACT risk groups but does not report multivariate analyses to adjust for potential confounders (e.g., age, comorbidities, cancer stage, ECOG performance status). Factors like female sex, identified as associated with poorer survival, may reflect confounding rather than true prognostic effects"

Response 2: Thank you for your comment. This paper was intended to be a formal validation of the PLaCT score in our Australian cohort, this was highlighted in both the methods and results section. In regards to multivariate analysis, the majority of the reviewers highlighted this as a weakness, and we have subsequently performed a multivariate analysis and made changes to the methods, results and discussion section, please see the changed. Thank you for your comment. 

 

Comment 3" The study does not report standard validation metrics such as discrimination (e.g., Harrell’s concordance probability or area under the receiver operating characteristic curve) or calibration (e.g., calibration plots or Hosmer-Lemeshow test). These metrics are essential to confirm that the PLACT score accurately distinguishes between risk groups and that predicted survival probabilities align with observed outcomes in the Australian cohort"

Response 3: Thank you for your comment. This paper was intended to be a formal validation of the PLaCT score in our Australian cohort, this was highlighted in both the methods and results section. In the future, particularly with a larger cohort, a formal validation could be performed. Thank you for your comment. 

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors

Thanks for your submission. I read your manuscript and have some questions and recommendations.

1- in your abstract, mentioned that you do subgroup analysis, but in limitations of the study, you clarified that due to small number of patients, were not able to do subdroup analysis. Please mention that on which variables you do subgroup analysis.

2- introduction section, line 70, figure 4 or figure 1??

3- material and method section, this sentence repeated twice." Data was collected from 1st of January 2018 to 31st of December 2023". Please omit one of them.

4- Table 2, Method of first stent , what is the meaning of "retrograde and antegrade"?

5- Table 3, you reported that 51 and 37 patients were survived 6 and 12 months post MUO treatment respectively, but when you reported improvement and worsening in renal function after 6 months, the number of patients were 47 and 48 respectively and after 12 months the number of patients that you reported for improvement in renal function were 36. What is the reason for this difference?

6- your manuscript should be reviewed by a native English speaker.

Author Response

Comment 1: "in your abstract, mentioned that you do subgroup analysis, but in limitations of the study, you clarified that due to small number of patients, were not able to do subdroup analysis. Please mention that on which variables you do subgroup analysis."

Response 1: Thank you for your comment. We did subgroup analysis on all the variables that we did the survival analysis on, and it generated very large data tables. We didn't think it would add  much value to the paper. However to address your comment we have added into the methods section that subgroup analysis was performed. We will make the  data  available on request to the corresponding author or through appendix items. Thank you. 

 

Comment 2: "introduction section, line 70, figure 4 or figure 1??"

Response 2: Thank you for identifying this error. It has been corrected to figure 1. 

 

Comment 3: "material and method section, this sentence repeated twice." Data was collected from 1st of January 2018 to 31st of December 2023". Please omit one of them"

Response 3: Thank you for identifying this, it has been corrected

 

Comment 4: "Table 2, Method of first stent , what is the meaning of "retrograde and antegrade"

Response 4: "Thank you for the comment. "Retrograde refers to insertion via a rigid cystoscope, whilst antegrade refers to ureteric stent insertion via a nephrostomy tract. This is described in the second paragraph of the introduction section. 

 

Comment 5: Table 3, you reported that 51 and 37 patients were survived 6 and 12 months post MUO treatment respectively, but when you reported improvement and worsening in renal function after 6 months, the number of patients were 47 and 48 respectively and after 12 months the number of patients that you reported for improvement in renal function were 36. What is the reason for this difference?

Response 5: Thanks for identifying this. The mismatched numbers are due to missing renal function data. We have added a missing data row into these points to clear up this confusion. Thank you. 

 

Comment 6: "Your manuscript should be reviewed by a native English speaker"

Response 6: Thank you. All 3 authors are native English speakers, we have proof read and will endeavour to improve the readibility further. 

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript frequently implies that renal decompression improves survival and facilitates further oncological treatment. However, the retrospective design inherently limits the ability to establish causality. The study lacks a control group of patients with MUO who did not undergo decompression, making it impossible to determine the true benefit of the intervention. The discussion acknowledges this limitation but doesn't adequately address the implications for the interpretation of results. The authors should revise the language throughout the manuscript to avoid overstating the benefits of decompression and focus on describing outcomes associated with the intervention rather than caused by it. Consider reframing the research question to focus on describing the outcomes and experiences of patients undergoing decompression for MUO, rather than assessing the effectiveness of the intervention itself.

The study acknowledges potential selection bias but does not discuss its potential impact on the findings. Were all consecutive patients with MUO during the study period included? If not, what were the criteria for selecting patients for intervention? Understanding the selection process is crucial for interpreting the generalizability of the results. The authors should provide more detail about the referral pathways and decision-making processes leading to intervention.

The univariate survival analysis does not account for potential confounding factors, such as age, cancer stage, and comorbidity, which could influence both the decision to intervene and survival outcomes. The authors should consider performing a multivariate survival analysis to adjust for these confounders. The Charleston Comorbidity Score is collected but not utilized in the analysis. This should be incorporated.

The level of detail in Table 4 is excessive. Consider summarizing the data and focusing on the most clinically relevant complications. Also, clarify the distinction between "total number of stent-related complications" (143) and the sum of the individual complications listed (which is less than 143).

The quality of Figure 1 (PLaCT Risk Classification Score) is poor and should be improved.

 

Comments on the Quality of English Language

There are some minor grammatical and stylistic errors throughout the manuscript that should be corrected.

Author Response

Comment 1: "The manuscript frequently implies that renal decompression improves survival and facilitates further oncological treatment. However, the retrospective design inherently limits the ability to establish causality. The study lacks a control group of patients with MUO who did not undergo decompression, making it impossible to determine the true benefit of the intervention. The discussion acknowledges this limitation but doesn't adequately address the implications for the interpretation of results. The authors should revise the language throughout the manuscript to avoid overstating the benefits of decompression and focus on describing outcomes associated with the intervention rather than caused by it. Consider reframing the research question to focus on describing the outcomes and experiences of patients undergoing decompression for MUO, rather than assessing the effectiveness of the intervention itself"

Response 1: Thank you for the comment. We agree that the lack of a control group means that no direct comparison may be drawn about whether renal decompression improves survival or renal function compared to no treatment. In the last paragraph in the the introduction, in keeping with your comment,  we have outlined that our goal is "aimed to describe" the outcomes of our cohort, rather than prove efficacy. In other parts of the introduction (fourth paragraph for example), we highlighted that renal decompression "may" relieve symptoms or allow continuation of oncological treatment, and in the discussion this was further explored, referring to some other studies that have shown conflicting results in regards to this. To address your comment in the manuscript, we have changed some of the language in the discussion to make it clear we are not trying to prove causality of renal decompression and improvement of survival, and added a sentence into the limitations and conclusion to make this clear. 

 

Comment 2: "The study acknowledges potential selection bias but does not discuss its potential impact on the findings. Were all consecutive patients with MUO during the study period included? If not, what were the criteria for selecting patients for intervention? Understanding the selection process is crucial for interpreting the generalizability of the results. The authors should provide more detail about the referral pathways and decision-making processes leading to intervention"

Response 2 : Thank you for the comment. We have added a couple of sentences into the methodology section to address your comment. We hope it clarifies your concerns. 

 

Comment 3: "The univariate survival analysis does not account for potential confounding factors, such as age, cancer stage, and comorbidity, which could influence both the decision to intervene and survival outcomes. The authors should consider performing a multivariate survival analysis to adjust for these confounders. The Charleston Comorbidity Score is collected but not utilized in the analysis. This should be incorporated"

Response 3: Thank you for your comment. A number of reviewers highlighted this fact. I have now performed a multivariate analysis and have made a number of edits throughout the manuscript discussing the results. Thank you.

 

Comment 4" The level of detail in Table 4 is excessive. Consider summarizing the data and focusing on the most clinically relevant complications. Also, clarify the distinction between "total number of stent-related complications" (143) and the sum of the individual complications listed (which is less than 143)"

Response 4: Thank you for the comment. We have attempted to simplify the table, and we  hope that it presents the data more clearly now. We calculated the sum of the individual complications and  it does add up to 143.. Thank you for your comment. 

 

Comment 5 "The quality of Figure 1 (PLaCT Risk Classification Score) is poor and should be improved."

Response 5 Thank you for your comment. I have adjusted the figure to appear similar to other tables in the manuscript.

Reviewer 4 Report

Comments and Suggestions for Authors

Thank you to the editor for the opportunity to review this manuscript. Overall, it is well written. The study is clinically relevant.

Author Response

Thank you for your review.

There are no comments to respond to. 

Reviewer 5 Report

Comments and Suggestions for Authors

I congratulate the authors on this well-written and well-designed retrospective cohort study. The study primarily focused on renal function and survival outcomes. As the authors noted, it did not address quality-of-life issues. Unfortunately, there are no sufficient prospective studies in the literature to evaluate the quality of life in patients with malignant ureteral obstruction who are followed with ureteral stents or percutaneous nephrostomy. Overall, the manuscript is suitable for publication, but I believe a few revisions would be beneficial:

1. The number of patients who received only percutaneous nephrostomy without any stent placement (unilateral or bilateral) is not clearly stated.

2. A total of 31 stent occlusions were reported in patients managed with stents; however, the manuscript does not provide information on the type of stents used (e.g., polyurethane, silicone, tumor stent, etc.).

Author Response

Comment 1: "The number of patients who received only percutaneous nephrostomy without any stent placement (unilateral or bilateral) is not clearly stated"

Response 1: Thank you for your review and comment. All patients had stents placed in this cohort as part of their initial decompression. Some were left nephrostomy dependent later on in their journey, but not initially. Wehave included a sentence in the results section to clarify this. Thank you you again for your review. 

 

Comment 2: A total of 31 stent occlusions were reported in patients managed with stents; however, the manuscript does not provide information on the type of stents used (e.g., polyurethane, silicone, tumor stent, etc.).

Response 2: Thank you for your comment. In the results section on complications we have added a sentence describing that all of our stents were just polyurethane. There were not specific anti-tumour stents used (e.g. “RUSCH” trademark branded stent).

Reviewer 6 Report

Comments and Suggestions for Authors

This study is a single-center retrospective investigation examining the significance of urinary tract decompression procedures (ureteral stent placement or nephrostomy) for malignant ureteral obstruction (MUO). It specifically focused on survival rates, renal function, and the burden of postoperative complications, evaluating the implementation of prospective patient registration, detailed clinical data analysis, and prognostic stratification using the PLaCT score. It holds significant clinical importance by providing concrete numerical data to aid the difficult clinical decision of "whether to relieve the obstruction," a frequent challenge in clinical practice. However, limitations exist, including single-center implementation, lack of multivariate analysis, and insufficient QOL assessment using objective measures. Notably, the absence of a non-intervention group and the lack of comparative evaluation of survival prognosis and QOL directly hinder the verification of whether MUO removal truly contributes to survival rates or QOL. This study concludes that MUO removal surgery "should not be performed in all cases; rather, it requires case-by-case selection based on prognosis and the tumor treatment plan." The authors state that while this procedure is meaningful in cases with life-threatening infections, renal failure, or planned future antitumor therapy, in other cases it is "often futile and carries significant burdens such as complications and hospitalization." This point is critically important for clinical practice.

The following outlines ideal aspects for improving this study. Note that these include purely ideal points and encompass items the authors already listed as "limitations."
1. Including analyses incorporating the natural course of patients who did not undergo MUO release would have demonstrated the actual value of this intervention.
2. Multivariate analysis should be performed to determine whether prognostic factors such as gender and emergency intervention are independent predictors.
3. Since the PLaCT score is a renal function assessment based on creatinine levels, the authors likely used creatinine values. However, assessment using eGFR, which can exclude the effects of gender and body size, would be ideal. Furthermore, the definition of "changes in renal function" is unclear and requires clarification. We would like to know the authors' perspective on whether this should be examined as a continuous variable or as a categorical variable, such as the improvement rate.
4. As a prerequisite for this study, QOL assessment is essential. It should clearly demonstrate the contribution to quality of life, not just survival time.
5. The analysis regarding cancer type is limited to distinguishing between urological cancers, gynecological cancers, and pelvic primary cancers. We would like to know the results of examining whether ureteral obstruction is extensive or localized, and whether it is mechanical obstruction or peristaltic dysfunction (e.g., peritoneal dissemination).
6. This reviewer recommends standardizing the number of decimal places reported for percentages and p-values.

Author Response

Comment 1: "Including analyses incorporating the natural course of patients who did not undergo MUO release would have demonstrated the actual value of this intervention"

Response 1: Thank you for your comment. We agree this would have been ideal. In the discussion we incorporated papers that did look at the natural course of such patients. In the future, a prospective study including patients who refuse or are denied treatment for various reasons would be good to include. Thank you for your comment. 

 

Comment 2: "Multivariate analysis should be performed to determine whether prognostic factors such as gender and emergency intervention are independent predictors"

Response 2: Thank you for your comment. This was recommended by many reviewers, and as such we have now performed a multivariate analysis. Please see the changes to the methods, results and discussion section. Thank you for your comment. 

 

Comment 3: Since the PLaCT score is a renal function assessment based on creatinine levels, the authors likely used creatinine values. However, assessment using eGFR, which can exclude the effects of gender and body size, would be ideal. Furthermore, the definition of "changes in renal function" is unclear and requires clarification. We would like to know the authors' perspective on whether this should be examined as a continuous variable or as a categorical variable, such as the improvement rate.

Response 3: Thank you for your comment. We have made amendments in the results tables to make it more clear what changes in renal function refers to. You are correct though that we used serum creatinine concentrations for the analyses. eGFR data has been recorded for all patients at all time points though, and if felt necessary to make this paper suitable for publication, we could also include this data. We chose to analyse changes in renal function as a categorical variable so that a reader could see roughly what proportion of their own patient they might expect to have either improvement or worsening of renal function. Thank you for your comment. 

 

Comment 4: As a prerequisite for this study, QOL assessment is essential. It should clearly demonstrate the contribution to quality of life, not just survival time.

Response 4: Thank you for pointing this out. We agree with this and have acknowledged this in the limitations. It is also weakness of the majority of the studies on this topic. We did record complications data as a surrogate for QoL assessment and plan to look at QOL specific measurements in future studies.Thank you for your comment. 

 

 

Comment 5: "The analysis regarding cancer type is limited to distinguishing between urological cancers, gynecological cancers, and pelvic primary cancers. We would like to know the results of examining whether ureteral obstruction is extensive or localized, and whether it is mechanical obstruction or peristaltic dysfunction (e.g., peritoneal dissemination)"

Response 5: Thank you for your comment. We have now updated the results section to include this information. 

 

Comment 6: "This reviewer recommends standardizing the number of decimal places reported for percentages and p-values"

Response 6: Thank you for your comment. We have now made amendments to standardise these numbers.