Intraurethral Steroid and Clean Intermittent Self-Dilatation for Lichen Sclerosus Proven Urethral Stricture Disease—A Retrospective Cohort Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study really is very interesting. However the results are not clearly give a good clinical conclusion to the readers. You present many statistical data concerning the improvement of max and Qol for different number of patients which should be limited for the total patients (plots images are enough). You do not mention any important clinical details like if the patients have stopped the ISC or how frequent do they perform them. How many patients have been treated without requiring more ISC. 

Comments on the Quality of English Language

52 CAN MANIFEST, CAN PRESENT

52 REMOVE “of bladder outlet obstruction can occur”

59 involved ENDOSCOPIC dilatations, direct vision optical

urethrotomy[6], meatoplasty, urethroplasty and in severe cass diversion perineal urethrostomy[7].

70 REPLACE “who do have” TO “with”

Author Response

Comment 1: "This study really is very interesting. However the results are not clearly give a good clinical conclusion to the readers. You present many statistical data concerning the improvement of max and Qol for different number of patients which should be limited for the total patients (plots images are enough)"

Thank you for your review and these comments!

• I have removed the tables of statistics, so now just the plots remain. I have added the p-value statistics into the descriptions of the plots. 
• In regards to clinical conclusions - I have added a sentence in the conclusion to convey to readers that patients need to continue CISC indefinitely on our regimen to maintain the effect of the steroids, and included a sentence in the results to inform the readers that patients continue to perform CISC once per month to maintain their disease.

Comment 2: You do not mention any important clinical details like if the patients have stopped the ISC or how frequent do they perform them. How many patients have been treated without requiring more ISC. 

• Thank you for highlighting this. I have included a sentence in the results section to convey to readers that the patients continue to perform CISC regularly (once per week to once per month) for maintenance of their stricture. Other than a patient who stopped due to poor tolerance, all other patients continued on CISC. I have also updated the methods section to convey to readers that our regimen suggested patients perform indefinite intermittent CISC once their stricture had stabilised for maintenance of the disease. Finally I have briefly addressed this in the discussion, suggesting that the indefinite aspect of the treatment is a negative aspect that needs to be considered when counselling patients about this treatment option

English Language Comments

52 CAN MANIFEST, CAN PRESENT

52 REMOVE “of bladder outlet obstruction can occur”

59 involved ENDOSCOPIC dilatations, direct vision optical

urethrotomy[6], meatoplasty, urethroplasty and in severe cass diversion perineal urethrostomy[7].

70 REPLACE “who do have” TO “with”

REPLY: Thank you for these suggestions, I have edited the manuscript accordingly. 

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors, 

I read this draft with great interest. My overal impression is that the format is acceptable, and the sections are written very well. The citations are appropriate and the discussion explains the findings of the study in  correctly. The limitations and strengths are noted. 

However, I have few comments for your consideration. 

1. In this retrospective study, data was mined from the records and clinical letters. The primary endpoint was the IPSS. My concerns are (i) only 12/18 men had IPSS results, hence, the analysis should involve only them, (ii) It is not clear when and how these patients filled the questionnaire (letter, GP practice, telephone clinic etc) and (iii) why you didn t contact these patients for an up-to-date results.
2. Further to my previous comment, I suggest that you  include the following outcomes flow rate, extent of disease, previous interventions, as well as LUTS-related medication. 

 

 

Author Response

COMMENT 1: In this retrospective study, data was mined from the records and clinical letters. The primary endpoint was the IPSS. My concerns are (i) only 12/18 men had IPSS results, hence, the analysis should involve only them, (ii) It is not clear when and how these patients filled the questionnaire (letter, GP practice, telephone clinic etc) and (iii) why you didn t contact these patients for an up-to-date results.

Thank you for your review and your comments. 

• I agree that the available data is not ideal. When the IPSS was performed, it was performed during their clinic review in the Urology outpatient clinic. Being a public teaching hospital, they were not always seen by our nurse practitioner or our reconstructive Urologist, they were often seen by junior registrars and sometimes more junior doctors, and I suspect their IPSS was not performed or not recorded in the notes. The majority of the patient records were on paper, and it is possible some of the IPSS questionairres were lost, leading to incomplete data. To make this more transparent, I will update the methodology (to highlight that the questionairres were performed in the Urology outpatient clinic), and make it clear in the limitations section of the discussion that this loss of data could  effect the reliability of the conclusions. 
• In regards to contacting the patients with up to date results, this being a retrospective study means that the time points to collect the data are well in the past now. There were occasions where patients did not attend their follow-up appointments, and so an IPSS could not be obtained. I again can make sure this appropriately reflected in the limitations section. 
• In regards to including only the 12 patients that completed pre-treatment questionairres, I agree that this makes the most sense from a methodological standpoint. Due to the small number of patients, and the loss of data, we compromised and thought the best way we could convey the outcomes was to pool the data at each time point even though this is a far less reliable measure of improvement. However, for example, some of the 12 patients who did their initial IPSS score, did not perform many of the follow-up scores (or they were lost or not performed), and some of the 6 patients who did not do the pre-treatment IPSS scores, did perform all of their follow-up scores. So whilst I agree this compromises the reliability of the data, I think this is the best way we could convey the success of our treatment with small numbers and loss of data. I have made edits to the manuscript to reflect this in the limitations section. 

 

COMMENT 2: Further to my previous comment, I suggest that you  include the following outcomes flow rate, extent of disease, previous interventions, as well as LUTS-related medication. 

• These would have been excellent metrics to record. I know that flow-rates were not routinely recorded during follow-up at the discretion of our reconstructive Urologist. We also did not record LUTS-related medication or previous interventions and given the short space of time for revisions, and the need to retrieve paper records, I will not be able to provide this information I am sorry. I have included a sentence on these in the limitations
• We did record data on the extent of disease, I have included a new table to display this information. 

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for the article. Can the authors address the following -

1. define the success rate - is that lack of intervention, flow rate, endoscopy findings or urethrogram ?
2. Add a paragraph on limitations of the study - small sample size, short follow up and incomplete data
3. what was the compliance of patients ? How can this be improved ? How long would the therapy continue for ?
4. Can the authors reference the protocol they used for instillation and frequency of CISC.
5. What are the options for failures ? Do they undergo urethroplasty -- was that more difficult ? or is diversion the only option ?
6. Was IPSS the only criteria to assess these patients ? Why was a uroflow not performed ?
7. Did the authors conduct a QOL on the patients and their view of having to CISC.

Author Response

Thank you for your review and your comments!

COMMENT 1:  Define the success rate - is that lack of intervention, flow rate, endoscopy findings or urethrogram?

• Success rate for us was lack of re-intervention, but also improvement in IPSS score.
• I will update the methodology to make this more clear, thank you!

COMMENT 2: Add a paragraph on limitations of the study - small sample size, short follow up and incomplete data

• Sorry I did have a limitations section buried in the last paragraph of the discussion. I have separated it and exanded it. Thank you!

COMMENT 3: What was the compliance of patients ? How can this be improved ? How long would the therapy continue for ?

• Compliance of the patients was excellent, in the results section I did highlight that only one patient stopped due to intolerance, and one patient had a period of non-compliance resulting in re-stricture, and repeated endoscopic dilatation. I will update the results section to make this more clear. Another reviewed had highlight duration of therapy as not being clearly addressed, I have updated the methods, results and discussion to make this more transparent. 

COMMENT 4: Can the authors reference the protocol they used for instillation and frequency of CISC.

• The protocol we used (which is our Urologists protocol) is in our methods section, we did not use a published protocol, or publish our own protocol sorry since this was retrospective. 

COMMENT 5: What are the options for failures ? Do they undergo urethroplasty -- was that more difficult ? or is diversion the only option?

• We were fortunate that we only had one patient who failed (following a period of non-compliance), his treatment was a repeat endoscopic dilatation (since he presented in extremis with urinary retention). He was re-offered definitive surgical management with urethroplasty but opted to re-engage with CISC which he has continued to do successfully since. 
• One patient who failed due to poor tolerance was not deemed a surgical candidate for urethroplasty, he fortunately has not had clinically significant re-stricturing. 
• As long as patients were surgical candidates - and agreeable, and their stricture was anatomically suitable, urethroplasty would be considered. If that was not a suitable option, perineal urethrostomy, or palliative management with intermittent endoscopic dilatations or direct vision optical urethrotomy would be the other options. I will address this in the methods. Thank you. 

COMMENT 6: Was IPSS the only criteria to assess these patients ? Why was a uroflow not performed ?

• IPSS was the only objective measure used. Uroflow was not performed mostly due to the majority of the follow-up period was when we had COVID restrictions in place which limited our ability to see patients face to face. The state health policies meant we mostly followed these patients up via telehealth unless an indication to be seen in person arose. 

COMMENT 7: Did the authors conduct a QOL on the patients and their view of having to CISC.

• We did not perform a formal QOL assessment, but this would be a very interesting aspect to consider in a future prospective study on this topic.