Robot-Assisted Radical Prostatectomy for Potential Cancer Control in Patients with Metastatic Prostate Cancer
, Makoto Kawase 2, Daiki Kato 2, Kota Kawase 2, Manabu Takai 2, Koji Iinuma 2, Keita Nakane 2, Noriyasu Hagiwara 3, Toru Yamada 4, Masayuki Tomioka 5 and Takuya Koie 2,*
Round 1
Reviewer 1 Report
Firstly, I would like to congratulate the authors for submitting their work. In a brief cohort of twelve patients, the authors demonstrate the usefulness of RRP for mPCa patients.
Following RRP, the 1- and 2-year biochemical recurrence-free survival rates were 83.3% and 66.7% respectively. Also, treatment-free survival rates at 1 and 2 years were 75.0% and 56.3% respectively. Only one patient developed de novo bone metastases 6.4 27 months postoperatively.
The study has merit. However, it has several issues. My comments are as follows:
Introduction: What did you hypothesize before conducting this study? Please write your hypothesis in 2-3 lines at the end of the Introduction section.
Methods: Well-written.
Results: The results are really interesting. However, the sample size is extremely small and the follow-up is very short.
-The results cannot be generalized to all cases of mPCa based on the findings in just twelve cases. This is the major limitation of this study.
-The study will be of merit if the authors add functional outcomes to it. Since the cohort is small (n=12), it is not difficult to do the same. I do not see any relevance of this study based on just the short-term oncological outcomes in twelve patients.
Discussion: The study has several limitations. Please mention them in detail.
Author Response
15, April, 2022
Dr. Editor
The Current Oncology
Dear Editor:
Thank you very much for the review of our manuscript titled “Robot-assisted radical prostatectomy for potential cancer control in patients with metastatic prostate cancer.”
We sincerely appreciate all valuable comments and suggestions, which helped us to improve the quality of our manuscript. Our responses to the Reviewers’ comments are described below in a point-to-point manner. Appropriate changes, suggested by the Reviewers, have been introduced to the manuscript (track-changes mode in the red color font). Let me emphasize our full readiness to make any further improvements to the manuscript.
We hope that our manuscript will be acceptable for publication in the Current Oncology.
We look forward to hearing from you.
Yours sincerely,
Takuya Koie
Corresponding author
Department of Urology
Gifu University Graduate School of Medicine
1-1 Yanagido, Gifu, Gifu 501-1194, Japan
TEL.: +81-582-30-6338
FAX: +81-582-30-6341
e-mail: [email protected]
Responses to the reviewer's comments
We would like to thank the Reviewers for taking the time and effort necessary to review the manuscript. We sincerely appreciate all the valuable comments and suggestions, which helped us to improve the quality of the manuscript.
Response to Reviewer 1
The authors appreciate the Academic Editor’s comments. The authors’ point-by-point responses to the comments are given below.
Firstly, I would like to congratulate the authors for submitting their work. In a brief cohort of twelve patients, the authors demonstrate the usefulness of RRP for mPCa patients.
Following RRP, the 1- and 2-year biochemical recurrence-free survival rates were 83.3% and 66.7% respectively. Also, treatment-free survival rates at 1 and 2 years were 75.0% and 56.3% respectively. Only one patient developed de novo bone metastases 6.4 27 months postoperatively.
The study has merit. However, it has several issues. My comments are as follows:
Introduction: What did you hypothesize before conducting this study? Please write your hypothesis in 2-3 lines at the end of the Introduction section.
Response:
The authors have added the following sentence on line 52:
Therefore, resection of the primary tumor with a continuous potential to metastasize, including promotion of growth factors and immunosuppressive cytokines, may have advantages of CRP even though the pathogenetic mechanisms involved in the advantageous effects of CRP are unclear [9].
The authors have added the Ref 9;
- Predina, J.D.; Kapoor, V.; Judy, B.F.; Cheng, G.; Fridlender, Z.G.; Albelda, S.M.; Singhal, S. Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness. J Hematol Oncol. 2012, 5, 34.
Results: The results are really interesting. However, the sample size is extremely small and the follow-up is very short.
-The results cannot be generalized to all cases of mPCa based on the findings in just twelve cases. This is the major limitation of this study.
Discussion: The study has several limitations. Please mention them in detail.
Response:
The authors have added the following sentences on line 207:
Second, the study had a strong vital weakness regarding the oncological advantages of CRP because a relatively limited number of patients were enrolled and the follow-up period was relatively short. Therefore, we reported no functional or long-term oncological outcomes. Additionally, we could not perform multivariate analysis to determine the predictive factor according to the improvement of oncological outcomes in patients with mPCa who received neoadjuvant therapy followed by CRP. Third, no control group of patients received radiation therapy or ADT alone for mPCa. Therefore, the CRP-related morbidity should be informed to the patient and shared decision making between the patient and physician after discussing the possible advantages and disadvantages should be encouraged. Finally, there was no standardized systemic treatment protocol before and after CRP. The conclusions are hypothesis generating.
-The study will be of merit if the authors add functional outcomes to it. Since the cohort is small (n=12), it is not difficult to do the same. I do not see any relevance of this study based on just the short-term oncological outcomes in twelve patients.
Response:
The authors have deleted the following sentences on line 200:
In another LoMP trial, patients with CRP developed fewer urinary symptoms than those with ADT [13]. Urinary stress incontinence was observed in 29.4% of the patients with CRP, whereas 6.8% had urge incontinence, 37.9% had obstructive voiding, and 6.8% had ureteric obstruction [13]. In this study, 91.7% of the patients had no urinary symptoms. Therefore, RP can have advantages over other treatment modalities for patients with PCa with urinary symptoms.
Author Response File: 
Author Response.docx
Reviewer 2 Report
This Study addresses an important question. Below are my questions/suggestions:
Abstract: Please mention the sample size
Line 31-32: Is there typo "present with new lesions on imaging" . Should this be "without new lesions"?
Line 57: Please mention the sample size
Please define in clear terms regarding "de-novo metastasis free survival" Does it mean new mets?
Please define in specific terms what do you mean by combined ADT, ARPI and chemo-hormonal treatment so that there is no confusion. This can go in the methods section
Please be consistent in terms of number of values after decimal. For PSA there are three, for others, it is one.
I think it is also important to know how did the patients respond at the sites of metastasis post the Neoadjuvant treatment (CR/PR/SD)? Gleason was 0 in 41% post Neoadjuvant therapy. Would be interesting to know how many had a CR at sites of metastasis? Also how was the response specifically in those who had a Gleason 0. Was is concordant or discordant with the response in the primary site?
Line 140: ADT is the treatment backbone for metastatic prostate cancer in general. Not sure if its appropriate to say specifically for "bone mets".
Line 178: Not clear. There seems to be an error/typo in terms of wording
Line 181: "Was" seems to be used wrong. Please correct the typo/Error in wording
What was the testosterone level before RP?
What was the severity of baseline Lower urinary tract symptomatology for the patients in this study prior to starting ADT, prior to proceeding with RP?
Again in Line 203: "mPCa who have achieved a serum PSA level <0.2 ng/mL and present with new lesions on computed tomography and bone scintigraphy." I am a bit confused. I understood that patients who had a great PSA response without new lesions were taken for RP, but if you read this line, it says the contrary. Because appearance of new lesions means, progression of disease while on ADT. Please clarify.
Author Response
15, April, 2022
Dr. Editor
The Current Oncology
Dear Editor:
Thank you very much for the review of our manuscript titled “Robot-assisted radical prostatectomy for potential cancer control in patients with metastatic prostate cancer.”
We sincerely appreciate all valuable comments and suggestions, which helped us to improve the quality of our manuscript. Our responses to the Reviewers’ comments are described below in a point-to-point manner. Appropriate changes, suggested by the Reviewers, have been introduced to the manuscript (track-changes mode in the red color font). Let me emphasize our full readiness to make any further improvements to the manuscript.
We hope that our manuscript will be acceptable for publication in the Current Oncology.
We look forward to hearing from you.
Yours sincerely,
Takuya Koie
Corresponding author
Department of Urology
Gifu University Graduate School of Medicine
1-1 Yanagido, Gifu, Gifu 501-1194, Japan
TEL.: +81-582-30-6338
FAX: +81-582-30-6341
e-mail: [email protected]
Responses to the reviewer's comments
We would like to thank the Reviewers for taking the time and effort necessary to review the manuscript. We sincerely appreciate all the valuable comments and suggestions, which helped us to improve the quality of the manuscript.
Response to Reviewer 2
The authors appreciate the Academic Editor’s comments. The authors’ point-by-point responses to the comments are given below.
This Study addresses an important question. Below are my questions/suggestions:
Abstract: Please mention the sample size
Response:
The authors have added the following part on line 22:
We conducted a retrospective study of twelve patients with mPCa
Line 31-32: Is there typo "present with new lesions on imaging". Should this be "without new lesions"?
Response:
The authors have changed “with” to “without.”
Line 57: Please mention the sample size
Response:
The authors have added the following part on line 60:
We retrospectively enrolled twelve patients with mPCa
Please define in clear terms regarding "de-novo metastasis free survival" Does it mean new mets?
The authors have added the following sentence on line 106:
De novo metastasis was defined as a new lesion after neoadjuvant therapy followed by CRP.
Please define in specific terms what do you mean by combined ADT, ARPI and chemo-hormonal treatment so that there is no confusion. This can go in the methods section
Response:
The authors have added the following sentence on line 71:
The patients received combination therapy including luteinizing hormone-releasing hormone agonists or antagonists (LHRH) and bicalutamide 80 mg/day as combined androgen blockade therapy, LHRH plus abiraterone 1000 mg/day or apalutamide 240 mg/day as androgen receptor pathway inhibitor therapy, and LHRH and tegafur-uracil 300 mg/day as chemohormonal therapy.
Please be consistent in terms of number of values after decimal. For PSA there are three, for others, it is one.
Response:
The authors have added the following part on line 99:
The date of disease recurrence and PSA failure were determined as the two consecutive PSA values that the date when the serum PSA level exceeded 0.2 ng/mL.
I think it is also important to know how did the patients respond at the sites of metastasis post the Neoadjuvant treatment (CR/PR/SD)? Gleason was 0 in 41% post Neoadjuvant therapy. Would be interesting to know how many had a CR at sites of metastasis? Also how was the response specifically in those who had a Gleason 0. Was is concordant or discordant with the response in the primary site?
Response:
The authors have added the following sentences on line 120:
The enrolled patients achieved primary site reduction and complete remission of lymph node metastasis after neoadjuvant therapy. Five patients had bone metastasis without new lesions on bone scintigraphy before CRP.
Line 140: ADT is the treatment backbone for metastatic prostate cancer in general. Not sure if its appropriate to say specifically for "bone mets".
Response:
The authors have revised the following part on line 153:
PCa with bone metastases → mPCa
Line 178: Not clear. There seems to be an error/typo in terms of wording
Response:
The authors have revised the following sentence on line 191:
CRP may have addressed several surgery-related complications serious problems, particularly the perioperative outcomes and urinary symptoms.
Line 181: "Was" seems to be used wrong. Please correct the typo/Error in wording.
Response:
The authors have revised the following sentence on line 194:
CRP in patients with mPCa may have was at a significantly higher rate for overall, intraoperative, genitourinary, and miscellaneous complications and blood transfusion compared to that in patients with localized PCa.
What was the testosterone level before RP?
Response:
The authors have added the following part on line 63:
serum prostate-specific antigen (PSA) and testosterone level,
The authors added the following part on line 76:
We confirmed that they had achieved a serum PSA level of <0.2 ng/mL, maintained a castration level (<50 pg/mL), and presented without new lesions on computed tomography and bone scintigraphy.
What was the severity of baseline Lower urinary tract symptomatology for the patients in this study prior to starting ADT, prior to proceeding with RP?
Response:
The authors have added the following sentence on line 119:
None of the enrolled patients had severe urinary tract symptoms before initiating neoadjuvant therapy or CRP.
Again in Line 203: "mPCa who have achieved a serum PSA level <0.2 ng/mL and present with new lesions on computed tomography and bone scintigraphy." I am a bit confused. I understood that patients who had a great PSA response without new lesions were taken for RP, but if you read this line, it says the contrary. Because appearance of new lesions means, progression of disease while on ADT. Please clarify.
Response:
The authors have changed “with” to “without.”
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
The authors have incorporated my comments in the revised version. The overall scientific quality of the manuscript has improved significantly. There are some pitfalls of the work which have been duly highlighted in the limitations section.
