The Goal of Achieving High-Quality Surgical First-Line Therapy in Patients with Penile Cancer Is Important; However, Some Collective Efforts Are Still Required in Order to Reach It. Comment on Brassetti et al. Combined Reporting of Surgical Quality and Cancer Control after Surgical Treatment for Penile Tumors with Inguinal Lymph Node Dissection: The Tetrafecta Achievement. Curr. Oncol. 2023, 30, 1882–1892
Round 1
Reviewer 1 Report
This paper comments on the paper by Brassetti et al. Penile cancer is classified as a rare cancer, so there should be a variety of opinions. The reviewer would like to suggest some critiques as follows.
1. On line 40, “Age was the only … interval: 1-6%)” is unclear. Please revise this sentence to make it clearer.
2. On line 70, #In addition, the inclusion … “circular reasoning error”” is unclear. Please revise this sentence to make it clearer.
3. On line 85, what is “ILD with 7+7 removed”?
4. On line 96, what is surgical tumor therapy? Tumor for surgical treatment?
5. On line 97, I don't think there is an established neoadjuvant therapy for penile cancer. What is the intention of this phrase?
Author Response
We sincerely thank the reviewer for his time spent reading our manuscript. We consider the 5 points listed by the reviewer to be very important and would like to thank him for this as well, as it gives us the opportunity to formulate our point of view even more clearly and precisely. We have responded to these five points point-by-point below. All changes in the manuscript have been indicated by us in green.
Matthias May (on behalf of the other authors of the manuscript)
Hint 1: On line 40, “Age was the only … interval: 1-6%)” is unclear. Please revise this sentence to make it clearer.
Reply: We thank you for the hint. In Table 2 of the original paper by Brassetti et al, the authors formed a multivariate logistic regression model in which achievement of the tetrafecta outcome was the model endpoint. Patient age represented the only factor in the multivariate regression model that independently predicted the end point. The OR was 0.97 with a 95% confidence interval of 0.94 to 0.99 (p=0.04). Since patient age was included as a continuous variable in the model, we could conclude that patients were relatively 3% (OR= 0.97) less likely to achieve the tetrafecta outcome (= all four criteria were met) per past year of life. In contrast, the 95% confidence interval (0.94-0.99) calculated by Brassetti et al. can be interpreted as a decrease of 1 to 6% per past year of life. In other words, approximately 2.5% of the study population showed only a 1% (or less) relative decrease in tetrafecta outcome per past year of life, but another 2.5% of the study population showed a 6% (or more) relative decrease.
We have adjusted the duplicate term "prediction" in our sentence so that our statement is more clearly understood.
Hint 2: On line 70, #In addition, the inclusion … “circular reasoning error”” is unclear. Please revise this sentence to make it clearer.
Reply: However, we consider this information from the expert to be absolutely important and would also like to thank him for this. On the other hand, we are already completely at the limit in the word count of 2000 words offered to us, so that we would like to leave the designation "circular reasoning error" as it is and cannot explain it further in the manuscript due to the word count limit. Any other term also in use, such as "self-fulfilling prophecy", does not hit the "bull's eye" exactly as the reference to the "circular reasoning error" given by us, in our opinion. If the reviewer and Editor-in-Chief deem "self-fulfilling prophecy" to be more comprehensible, we fully concur that our sentence may be modified accordingly. It constitutes a circular reasoning fallacy and lacks scientific validity to infer from a time-dependent endpoint (NED at 12 months) to another time-dependent endpoint (ACM at 24 months). In this regard, one could invert the circle and assert that the patients who survive at 24 months (ACM of 0%) are also those who do not experience disease recurrence at 12 months (NED of 0%). The correlation between these two endpoints is so close that it amounts to a circular reasoning fallacy to use "NED-12 months" as a predictor of the "ACM-24 months" endpoint. To clarify our point, we have revised the term "circular reasoning fallacy."
Hint 3: On line 85, what is “ILD with 7+7 removed”?
Reply: Thank you very much for this feedback. As we had already defined the term "ILND" as "inguinal lymph nodes dissection" in line 55, we have now further clarified our statement "7+7 ILN" by specifying that the 7 always refer to one groin ("7 ILNs per groin"). This should eliminate any potential misunderstandings and allow for a clear interpretation.
Hint 4: On line 96, what is surgical tumor therapy? Tumor for surgical treatment?
Reply: A thousand thanks for this feedback. We truly appreciate the reviewer's suggestion, as it helped us recognize that our phrasing was not as precise as it could have been. We gladly incorporated the reviewer's wording and revised our manuscript accordingly.
Hint 5: On line 97, I don't think there is an established neoadjuvant therapy for penile cancer. What is the intention of this phrase?
Reply: We are once again entirely in agreement with the assessor's perspective. In general, chemotherapy has a poor response rate in PECa, and the research in the neoadjuvant indication (neoadjuvant chemotherapy = NAC) is highly limited. Nevertheless, the current EAU and ASCO guidelines formulate the following recommendation: 'Offer neoadjuvant chemotherapy using a cisplatin- and taxane-based combination to chemotherapy-fit patients with pelvic lymph node involvement or those with extensive inguinal involvement (cN3), in preference to up front surgery.' (EAU-ASCO Collaborative on Guidelines on Penile Cancer). For this reason, despite the poor NAC results also mentioned by the reviewer, we would like to retain our wording.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Dear Authors,
I read with interest your letter and I found it very sound. No further points should be discussed in my opinion
Author Response
We sincerely thank the reviewer for his time spent reading our manuscript. Taking his review into account, there are no points that need to be changed in our manuscript.
We would also like to thank the reviewer for this.
Kindest regards, Matthias May (on behalf of the other authors of the manuscript)
