SIU-ICUD: Comprehensive Imaging in Prostate Cancer—A Focus on MRI and Micro-Ultrasound

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors, 

In the Methodology section in abstract a mention on selection criterion of studies can be made. This can be elaborated in the main text .To also include biases in the literature reviewed

A statement mentioning the need for the study like a brief mention of the gap in current clinical practice or challenges in integrating these technologies into standard care in in the introduction would be impactful

A table with comparative data on sensitivity, specificity, limitations, clinical outcomes, cancer detection rates, biopsy avoidance rates.and other variables for mpMRI & MicroUS would be useful

Cost effectiveness can be added in the conclusion as well

 

Comments on the Quality of English Language

Kindly ensure consistent use of terminology throughout the manuscript (e.g., "MRI" vs. "mpMRI", "MicroUS" vs. "Micro-ultrasound").

There are some typographic and grammatical errors in the manuscript

Author Response

Dear reviewers, thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files
Point-by-point response to Comments and Suggestions for Authors
Reviewer 1 : “In the Methodology section in abstract a mention on selection criterion of studies can be made. This can be elaborated in the main text .To also include biases in the literature reviewed”. Response: Thank you for your thoughtful feedback. Although the point raised by the reviewer is illuminating from a methodological and statistical standpoint, this narrative review is based on the consensus of an expert panel rather than a systematic review or meta-analysis. As such, there was no formal methodology for study selection. For this very reason we have respectfully decided to not incorporate the aforementioned suggestion in the revised version of the manuscript.   Reviewer 1: “A statement mentioning the need for the study like a brief mention of the gap in current clinical practice or challenges in integrating these technologies into standard care in in the introduction would be impactful”. Response: Thank you for your insight. We have now added the statement required in the revised version of the manuscript, chapter 1 which now states:” Despite these advancements, challenges remain in fully integrating these imaging technologies into standard clinical practice. Variability in accessibility, cost, operator dependency, and the need for standardized interpretation limit their widespread adoption. Furthermore, there is an ongoing need to refine patient selection criteria and optimize the diagnostic workflow to balance sensitivity, specificity, and clinical utility. We aim to summarize the evidence supporting these imaging tools and their roles in optimizing the diagnostic workflow for PCa.”   Reviewer 1: “A table with comparative data on sensitivity, specificity, limitations, clinical outcomes, cancer detection rates, biopsy avoidance rates and other variables for mpMRI & MicroUS would be useful. Cost effectiveness can be added in the conclusion as well” Response: Thank you for your insightful comments. We appreciate your suggestion to include a comparative table summarizing sensitivity, specificity, limitations, clinical outcomes, cancer detection rates, and biopsy avoidance rates for mpMRI and MicroUS. However, given the narrative nature of this paper, which is based on the perspectives of an expert panel rather than a systematic review or meta-analysis, such a summary table falls outside the scope of our study. Additionally, while cost-effectiveness is a crucial aspect of clinical decision-making, there is currently insufficient data in the literature to provide a robust analysis of the cost-effectiveness of MicroUS compared to mpMRI. As such, we are unable to address this aspect in our conclusions. We sincerely appreciate your thoughtful feedback, and we hope this clarification is helpful.   Reviewer 1: “Kindly ensure consistent use of terminology throughout the manuscript (e.g., "MRI" vs. "mpMRI", "MicroUS" vs. "Micro-ultrasound"). There are some typographic and grammatical errors in the manuscript” Response: We have addressed the grammatical errors as well as the terminology.

Reviewer 2 Report

Comments and Suggestions for Authors

The overall review is good and does look an important aspect of investigation of prostate cancer. 
comments

1) need inclusion of role of both mpMRI and micro USS in assessing recurrent disease, especially in a clinical post RT recurrence.

2) in Paragraph 5, from line 158 there has to be statement about poor negative predictive value of mpMRI in local staging of prostate cancer. It is mentioned but not emphasised enough. Also the issues of lymph node staging needs further discussion. 
3) spelling mistake in line 299, it should be MicroUs rather than Microus

4) spelling mistake in line 309, it should be operator-dependent rather than Oerator-dependent. 

Author Response

Dear reviewers, thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files

Point-by-point response to Comments and Suggestions for Authors

Reviewer 2: “need inclusion of role of both mpMRI and micro USS in assessing recurrent disease, especially in a clinical post RT recurrence”.

Response: We thank the reviewers comments. We have now extensively revised paragraph 5 which now states: “Precise locoregional staging of PCa at the time of diagnosis is crucial for optimizing treatment strategies and avoiding both overtreatment and undertreatment. The TNM classification system is used to determine the extent of PCa spread. Currently, PCa staging is primarily based on serum PSA levels, digital rectal examination (DRE), and Gleason score, which can sometimes underestimate the true extent of disease. Extracapsular extension and seminal vesicle invasion are associated with an increased risk of biochemical recurrence following definitive treatment due to a greater likelihood of positive surgical margins and lymph node metastases. The ability to accurately identify ex-traprostatic disease using mpMRI allows for more precise surgical planning, potentially reducing the incidence of positive margins in final pathology. For patients with T3a disease, standard treatment options include radical prostatectomy or brachytherapy. However, managing T3b disease often necessitates a multimodal approach incorporating long-term androgen deprivation therapy along with definitive treatment. The ability to localize seminal vesicle and regional invasion with mpMRI facilitates tailored therapeutic decisions. A study involving 532 patients who underwent mpMRI prior to MRI-ultrasound fusion biopsy (MRUSFBx) and radical prostatectomy demonstrated that incorporating mpMRI into clinical nomograms improved the predictive accuracy for organ-confined disease, extraprostatic extension, seminal vesicle invasion, and lymph node involvement. A me-ta-analysis of 75 studies assessing the accuracy of mpMRI in PCa staging reported sensitivity and specificity values of 0.57 and 0.91 for detecting extraprostatic disease and 0.58 and 0.96 for seminal vesicle invasion. These findings highlight mpMRI's high specificity for locoregional staging, though a negative scan does not necessarily rule out extraprostatic disease. Various scoring systems have been developed to assess the likelihood of extraprostatic extension on mpMRI, including the European Society of Urogenital Radiology score, the Likert scale, tumor contact length, and extraprostatic extension grade. A retrospective study comparing these criteria emphasized the value of extraprostatic extension grade, which integrates both quantitative and qualitative mpMRI parameters while being less dependent on the radiologist’s experience. Additionally, recent research has identified the capsular enhancement sign on DCE MRI as a highly specific marker for extraprostatic extension. Further studies are needed to refine the most sensitive and specific parameters for identifying extraprostatic spread. A hypointense signal on T2-weighted imaging (T2WI), restricted diffusion on DWI, and early enhancement on DCE MRI may indicate seminal vesicle invasion and infiltration of adjacent structures. However, the ability of mpMRI to detect nodal metastases remains limited due to its restricted field of view compared to whole-body imaging techniques. Relying solely on lymph node size to distinguish between malignant and benign nodes can lead to both false positives (e.g., inflammatory lymphadenopathy) and false negatives (e.g., micro metastases below the detection threshold). Traditionally, PCa staging has included computed tomography (CT) and bone scintigraphy to assess nodal and distant metastases. However, novel imaging techniques such as prostate-specific membrane antigen positron emission tomography (PSMA PET) have demon-stated improved accuracy. In a study of 764 men with intermediate- to high-risk PCa undergoing PSMA PET before radical prostatectomy, the sensitivity and specificity for detecting pelvic nodal metastases were 0.40 and 0.95, respectively. This suggests that PSMA PET provides high specificity for detecting nodal disease, though small metastases may still go undetected, meaning a negative scan does not entirely exclude nodal involvement. The role of MRI in detecting local recurrence after radical prostatectomy is also being increasingly recognized. Furthermore, functional MRI with diffusion and perfusion imaging, has shown potential in identifying local recurrence even at low PSA levels. This capability is clinically significant as early detection of recurrence can alter management strategies, particularly in the context of salvage radiation therapy (SRT). MRI has been shown to outperform CT in delineating local recurrences and defining target volumes for radiation therapy, potentially enabling dose escalation while minimizing toxicity. Furthermore, dynamic contrast-enhanced (DCE) MRI and DWI have been identified as effective tools in distinguishing between recurrent tumor tissue and post-surgical fibrosis. [15–22].

Response: We have furthermore revised paragraph 12 which now states:” However, MicroUS has limitations in staging pelvic lymph nodes, bony structures, and detecting recurrence, areas where MRI remains superior”.

Reviewer 2: in Paragraph 5, from line 158 there has to be statement about poor negative predictive value of mpMRI in local staging of prostate cancer. It is mentioned but not emphasised enough. Also the issues of lymph node staging needs further discussion.

 

Response: Thank you for your insight. We have extensively revised paragraph 5. Please see the previous response.

 

Reviewer 2: spelling mistake in line 299, it should be MicroUs rather than Microus. spelling mistake in line 309, it should be operator-dependent rather than Oerator-dependent. 

Response: We have addressed the spelling mistakes.

Reviewer 3 Report

Comments and Suggestions for Authors

This is a narrative review on 2 imaging for prostate, namely mpMRI and microUS, the overall content was quite comprehensive. my comments:

1. for the mpMRI part, I think the overall content is quite complete, but I would like to suggest adding a discussion on the management of those with elevated PSA but with no PIRADS 3-5 lesion situation, the chance of missing cancer for this group of patients.
2. MicroUS seem to be the term used for micro-ultrasound, and so we might need to unify the appearance in the heading 8-11 ("Microus")
3. as MicroUS may be relatively new to some readers, the author might also discuss whether it has another role in clinical medicine. This is because, for MRI, while it is expensive, it could be used by other specialities, but the cost consideration of just purchasing one MicroUS for prostate might be a concern for some centres
4. the discussion on training and inter-observer variation might be a bit brief, as this is a concern for many users (as it might be the urologist who use this for biopsy)
5. a typo line 309 Oerator-dependent, should be operator

Author Response

Dear reviewers, thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files

Point-by-point response to Comments and Suggestions for Authors

Reviewer 3: “MicroUS seem to be the term used for micro-ultrasound, and so we might need to unify the appearance in the heading 8-11 ("Microus")”

Response: Thank you. We have addressed this issue.

Reviewer 3: “as MicroUS may be relatively new to some readers, the author might also discuss whether it has another role in clinical medicine. This is because, for MRI, while it is expensive, it could be used by other specialities, but the cost consideration of just purchasing one MicroUS for prostate might be a concern for some centres”

Response: Thank you for your thoughtful suggestion. While we recognize that MicroUS may have potential applications beyond prostate imaging, the primary focus of this paper is its role in prostate cancer detection and diagnosis. Within this scope, we have already discussed its clinical applications in biopsy guidance, active surveillance, and staging, which we believe sufficiently addresses its relevance in urological practice. Furthermore, given the word limit constraints, we aim to maintain a focused discussion on the key aspects of MicroUS in prostate cancer management. Expanding further into its broader clinical applications would go beyond the intended scope of this review. We appreciate your insight and trust that the current discussion provides a balanced and comprehensive overview of MicroUS within the context of prostate cancer diagnosis.

Reviewer 3 “a typo line 309 Oerator-dependent, should be operator”

Response: We have now addressed the typo.