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Review
Peer-Review Record

Optimizing Inguinal Lymph Node Dissection for Penile Cancer: A Pathway to Improve Outcomes and Complications—A Narrative Review

Complications 2025, 2(3), 20; https://doi.org/10.3390/complications2030020
by Federico Eskenazi 1,†, Luis G. Medina 2,†, Roberto Soto Suarez 1, Laura Fumero 1, Alegría C. Lusinchi Delfino 1, Keval Patel 3, Marcos Tobias Machado 4, Randall Lee 5 and Rene Sotelo 1,*
Reviewer 1:
Reviewer 2: Anonymous
Complications 2025, 2(3), 20; https://doi.org/10.3390/complications2030020
Submission received: 3 June 2025 / Revised: 18 July 2025 / Accepted: 30 July 2025 / Published: 4 August 2025

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors, 

You have compiled useful and practical information focussed at a surgery notorious for high rates of complications. Following are some comments and suggestions :

Strengths:

  • Comprehensive narrative review that outlines the evolution
  • Emphasis on the need of including CALI classification for standardization

Suggestions :

  • The lack of standardization in reporting complications can be highlighted in the introduction
  • The clinical gaps in this domain can be depicted as a table
  • A table comparing complication rates across techniques could be added. (traditional vs. VEIL vs. robotic assisted).
  • Strategies for whom the usage and selection criterion is not well defined (Eg : glue embolization) can be encouraged as potential areas of research
  • If any images are being planned, the section on lymphedema could include some – clinical images, measurement equipment, garments etc
  • Role of preemptive lymphedema management can be borrowed from studies on upper limb in breast cancer – potential areas of research
  • The emphasis on multidisciplinary management early in the course of treatment to prevent or manage complications can be brought in in the main text instead of the conclusion

Author Response

Reviewer 1:  

Strengths:

  • Comprehensive narrative review that outlines the evolution
  • Emphasis on the need of including CALI classification for standardization

We appreciate the reviewer for taking the time to revise our manuscript and for their positive feedback.

Suggestions:

  • The lack of standardization in reporting complications can be highlighted in the introduction

Thank you for this revision. We have added two lines (48-50) within the introduction section.

  • The clinical gaps in this domain can be depicted as a table

Thank you for your valuable recommendation. We added a section

(lines 272-289) before the conclusion section, named “Gaps in Knowledge and Potential Research Areas” where we quickly mention the gaps mentioned along the review, in addition to building a table (Table 2) to better demonstrate their implications.

  • A table comparing complication rates across techniques could be added. (traditional vs. VEIL vs. robotic assisted).

We appreciate your recommendation. We made a table (Table 1) comparing minor and major complications of open, VEIL, and RA-VEIL approaches, in addition to a few comments on each procedure.

  • Strategies for whom the usage and selection criterion is not well defined (Eg : glue embolization) can be encouraged as potential areas of research

Thanks for your comment, we added this to the “Gaps in Knowledge and Potential Research Areas” section.

  • If any images are being planned, the section on lymphedema could include some – clinical images, measurement equipment, garments etc
  • Thank you so much for your comments. Unfortunately, our team does not have those images at the time, but we will work on acquiring them for future publications.

Role of preemptive lymphedema management can be borrowed from studies on upper limb in breast cancer – potential areas of research

Thanks for your suggestion. Lines 178-186 describe preventive as well as possible management for lymphedema, these are also utilized on the upper limb for breast cancer.

  • The emphasis on multidisciplinary management early in the course of treatment to prevent or manage complications can be brought in in the main text instead of the conclusion

Thank you for your suggestion. We have added two lines (155 and 156) emphasizing this point in the main manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript examines the evolution in managing the inguinal lymph nodes in penile cancer and show some significance, while as a review, the manuscript should include the latest research about the topic, while the reference in the current manuscript are too old

Author Response

Reviewer 2:

Comments and Suggestions for Authors

This manuscript examines the evolution in managing the inguinal lymph nodes in penile cancer and show some significance, while as a review, the manuscript should include the latest research about the topic, while the reference in the current manuscript are too old

We appreciate your time and insights. We have included data from 1940, as the idea was to give an overview of the history of inguinal lymph node dissection and management of penile cancer. However, we have also included the latest research on the topic as the database search extended up to February 2025.

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors,

Your review, 'Optimizing Inguinal Lymph Node Dissection for Penile Cancer: A Pathway to Improve Outcomes and Complications—A Narrative Review', offers a relevant historical compilation on clinical features of different strategies for handling Lymph Node Dissection in patients with Penile Cancer. Nevertheless, I believe some modifications are required to match the holistic and multidisciplinary approach mentioned in the conclusions of this manuscript. Please consider the following comments.

Major comments

1. Some statements in this review require proper citation. For instance, the claim that "Penile cancer is an uncommon malignancy, accounting for 0.04 to 0.06% of all male carcinomas" should be supported by a relevant reference.

2. Please include the exact literature search strategy (prompt) used to retrieve studies related to penile cancer, along with the date on which the search was conducted.

3. Additionally, indicate the reference source used to determine the levels of evidence (Levels 1–4) applied in this review.

4. Based on the narrative presented in Section 2.1, Evolution and Innovations in Lymph Node Management, there appears to be a gap in the cited literature between 1990 and 2014. Please address this gap by incorporating relevant publications from that period.

5. Review the reference list for consistency and completeness. References 15, 16, and 19, among others, are missing or not cited in the text.

6. Verify that the reference for Horenblas et al. is properly included. Although it appears in Figure 1, it could not be located in the main reference list.

7. This review would benefit from the addition of a schematic or tabular summary highlighting the advantages and disadvantages of each lymph node management strategy.

8. In addition to the discussion of potential risks associated with ILND and SLNB techniques, please incorporate current evidence on molecular, biochemical, clinical, or hematological markers that may help predict regional lymph node metastasis in penile cancer.

Author Response

Reviewer 3:

Dear authors,

Your review, 'Optimizing Inguinal Lymph Node Dissection for Penile Cancer: A Pathway to Improve Outcomes and Complications—A Narrative Review', offers a relevant historical compilation on clinical features of different strategies for handling Lymph Node Dissection in patients with Penile Cancer. Nevertheless, I believe some modifications are required to match the holistic and multidisciplinary approach mentioned in the conclusions of this manuscript. Please consider the following comments.

 

We appreciate your review and time. We have considered and included your revisions to our manuscript accordingly.

Major comments

  1. Some statements in this review require proper citation. For instance, the claim that "Penile cancer is an uncommon malignancy, accounting for 0.04 to 0.06% of all male carcinomas" should be supported by a relevant reference.

Thank you for your observation. We have added the appropriate reference (Line 38).

  1. Please include the exact literature search strategy (prompt) used to retrieve studies related to penile cancer, along with the date on which the search was conducted.

Thank you for your comment. As this manuscript is a narrative review, we did not use a structured systematic search protocol. However, we did perform a broad literature search using Google Scholar, Embase, and PubMed databases with the following general terms: “Inguinal lymph node dissection”, “ILND”, or “Inguinal lymphadenectomy”, and “Radical”, “Modified”, “VEIL”, “RAVEIL”, or “Complications” covering the period from 1940 to December 2024. (lines 59-62)

  1. Additionally, indicate the reference source used to determine the levels of evidence (Levels 1–4) applied in this review.

Thank you for your valuable recommendation. The levels of evidence were determined based on the Oxford Centre for Evidence-Based Medicine (CEBM) 2011 classification System (lines 62-63)

  1. Based on the narrative presented in Section 2.1, Evolution and Innovations in Lymph Node Management, there appears to be a gap in the cited literature between 1990 and 2014. Please address this gap by incorporating relevant publications from that period.

We appreciate your comment. However, the 1990–2014 gap is addressed both within the main text and in Figure 1. To improve clarity and continuity, we have also added the corresponding dates in lines 93 and 99 for easier reference.

  1. Review the reference list for consistency and completeness. References 15, 16, and 19, among others, are missing or not cited in the text.

We appreciate your observation. We have reviewed and revised all reference citations and made sure these were appropriately cited within the manuscript

  1. Verify that the reference for Horenblas et al. is properly included. Although it appears in Figure 1, it could not be located in the main reference list.

We appreciate your valuable comment. Horenblas’ reference has been added as reference number 25.

  1. This review would benefit from the addition of a schematic or tabular summary highlighting the advantages and disadvantages of each lymph node management strategy.

We have added a table (Table 1) that depicts minor and major complication rates of each approach, in addition to commentaries on each.

  1. In addition to the discussion of potential risks associated with ILND and SLNB techniques, please incorporate current evidence on molecular, biochemical, clinical, or hematological markers that may help predict regional lymph node metastasis in penile cancer.

Thank you for your suggestion. In response, we have incorporated circulating tumor DNA (ctDNA) as a promising area of research for predicting metastasis and guiding management, as reflected in lines 285 to 290

 

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors,

Your review, 'Optimizing Inguinal Lymph Node Dissection for Penile Cancer: A Pathway to Improve Outcomes and Complications—A Narrative Review', offers a relevant historical compilation on clinical features of different strategies for handling Lymph Node Dissection in patients with Penile Cancer. Thank you for having replied to my previous comments. 

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