The Relationship between D’Amico and ISUP Risk Classifications and 68Ga-PSMA PET/CT SUVmax Values in Newly Diagnosed Prostate Cancers
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe paper is a retrospective review of a series of PET PSMA in patients diagnosed with prostate cancer (PC). Authors reported the main limitations of the study. PET PSMA findings correlate with PSA and Gleason score. Moreover, SUV of the prostate gland correlates with presence/absence of metastases. Patients with higher PSA and higher SUV in the prostate harbour a significantly increased risk of metastases. Besides, metastases were also found in 7 patients with Gleason score 6. I have therefore a question. Were those patients re-biopsied to confirm the Gleason score? Were metastases confirmed by other imaging modalities (bone scan, MR or CT scan), especially in the latter subset of patients? Finally, table 1 should be reviewed.
Author Response
Comments 1: The paper is a retrospective review of a series of PET PSMA in patients diagnosed with prostate cancer (PC). Authors reported the main limitations of the study. PET PSMA findings correlate with PSA and Gleason score. Moreover, SUV of the prostate gland correlates with presence/absence of metastases. Patients with higher PSA and higher SUV in the prostate harbour a significantly increased risk of metastases. Besides, metastases were also found in 7 patients with Gleason score 6. I have therefore a question. Were those patients re-biopsied to confirm the Gleason score?
Answer 1: First of all, thank you very much for your valuable comments. You are right, unfortunately the biopsy was not repeated.
Comment 2: Were metastases confirmed by other imaging modalities (bone scan, MR or CT scan), especially in the latter subset of patients?
Answer 2: Patients with suspected metastasis were evaluated with additional radiological images. However, we did not find additional examination necessary in patients with obvious metastatic appearance.
Comment 3: Finally, table 1 should be reviewed.
Answer 3: Table 1 has been revised.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript is interesting but some points should be improved:
1. The Authors should report in the Introduction the SUVmax cut-offs suggested in the literature to perform PSMA targeted prostate biopsy (Pepe P, Pepe L, Tamburo M, Marletta G, Savoca F, Pennisi M, Fraggetta F. 68Ga-PSMA PET/CT and Prostate Cancer Diagnosis: Which SUVmax Value? In Vivo. 2023 May-Jun;37(3):1318-1322. doi: 10.21873/invivo.13211. PMID: 37103095; PMCID: PMC10188025)
2. Digital-rectal examination should be added in Materials and Methods or in Table 1
3. The Authors should report PSMA PET/CT data and SUVmax of suspicious metastases: nodes vs. bone vs. visceral lesions. PCa Clinical staging can not be based on intraprostatic SUVmax value
4. The Authors should report the false negative rate of PSMA PET/CT in the staging of ductal prostatic carcinoma
5. D'Amico and not Damico
6. Results: revise percentages "In patients with a Gleason score of 9, 69% had metastasis, while 128 40% did not".
In the Discussion the authors should report the detection rate for PCa using PSMA targeted biopsy and the advantages of PSMA PET/CT in diagnosis and staging men at high risk for PCa
7. Table 1 should be revised: PSA and SUVmax values shoud be reported for each Grade Group PCa
8. The conclusions should be revised using all PSMA PET/CT data including also intraprostatic SUVmax for PCa staging.
10. In the Discussion the authors should report the detection rate for PCa using PSMA targeted biopsy and the advantages of PSMA PET/CT in diagnosis and staging men at high risk for PCa
Author Response
First of all, thank you very much for your valuable comments.
Comments 1: The Authors should report in the Introduction the SUVmax cut-offs suggested in the literature to perform PSMA-targeted prostate biopsy (Pepe P, Pepe L, Tamburo M, Marletta G, Savoca F, Pennisi M, Fraggetta F. 68Ga-PSMA PET/CT and Prostate Cancer Diagnosis: Which SUVmax Value? In Vivo. 2023 May-Jun;37(3):1318-1322. doi: 10.21873/invivo.13211. PMID: 37103095; PMCID: PMC10188025)
Answer 1: Our patients were those who had previously been diagnosed with prostate cancer through prostate biopsy. Ga68 PSMA PET/CT was performed at least 1 month after the prostate biopsy. The patients were not diagnosed with prostate cancer through PSMA PET/CT. In our country, PSMA PET/CT is not used in prostate diagnosis because insurance does not cover it.
Comments 2: Digital-rectal examination should be added in Materials and Methods or Table 1
Answer 2: The digital-rectal examination has been added to the materials and methods section.
Comments 3: The Authors should report PSMA PET/CT data and SUVmax of suspicious metastases: nodes vs. bone vs. visceral lesions. PCa Clinical staging can not be based on intraprostatic SUVmax value
Answer 3: Median SUVmax values ​​of metastases are included in the text.
Comments 4: The Authors should report the false negative rate of PSMA PET/CT in the staging of ductal prostatic carcinoma
Answer 4: If I understood your comment correctly, we wrote the negative predictive value in Table 3. The negative predictive value was calculated as 82.4%.
Comments 5: D'Amico and not Damico
Answer 5: Damico corrected to D'Amico
Comments 6: Results: revise percentages "In patients with a Gleason score of 9, 69% had metastasis, while 128 40% did not".
In the Discussion the authors should report the detection rate for PCa using PSMA targeted biopsy and the advantages of PSMA PET/CT in diagnosis and staging men at high risk for PCa.
Answer 6: Percentages have been corrected both in Table 1 and in the text.
Comments 7: Table 1 should be revised: PSA and SUVmax values should be reported for each Grade Group PCa
Answer 7: Table 1 was revised. Median SUVmax and median PSA values ​​were written for each group.
Comments 8: The conclusions should be revised using all PSMA PET/CT data including also intraprostatic SUVmax for PCa staging.
Answer 8: In our country, insurance only covers Ga68-PSMA PET/CT scans for patients diagnosed with prostate biopsy. Since all patients in our study underwent PSMA PET/CT after diagnosis with biopsy, we cannot perform PSMA-targeted biopsy.
Comments 9: In the Discussion, the authors should report the detection rate for PCa using PSMA targeted biopsy and the advantages of PSMA PET/CT in diagnosis and staging men at high risk for PCa
Answer 9: Since Ga68 PSMA PET/CT is currently used in patients with diagnosed prostate cancer, PSMA-targeted prostate biopsy is not on our agenda at the moment.
Reviewer 3 Report
Comments and Suggestions for AuthorsThe authors evaluate correlation with Ga68 PSMA-PET/CT SUVmax of prostate gland and D’Amico classification, ISUP grade, PSA value and status of metastasis. They also analyzed usefulness of PSA and Ga68 PSMA-PET/CT SUVmax of prostate gland as a predictive value of diagnosing metastasis. Interesting findings of this study are that Ga68 PSMA-PET/CT SUVmax of prostate gland correlated with metastasis. However, the authors did not discuss why Ga68 PSMA-PET/CT SUVmax of prostate gland correlated with metastasis. They should more deeply discuss this question according to biological aspects.
Major
ü Introduction should be more comprehensive. The authors should add some description about D’Amico and ISUP classification, how they are used and what is the problem that should be overcome.
ü D’Amico classification was developed for localized prostate cancer patients who received radical treatment and it classified them into low, intermediate and high risk according to recurrent risk. Thus, it is not accurate classifying prostate cancer patients with metastasis.
The following sentence does not make sense. “While 97 49% of high-risk patients had metastasis, 51% did not. Metastasis was present in 7% of 98 medium-risk patients, while it was absent in 93%. Metastasis was present in 6% of low-99 risk patients, but not in 94%.”
Minor
ü Damico should be D’Amico.
Author Response
First of all, thank you very much for your valuable comments.
Comments 1: The authors evaluate the correlation with Ga68 PSMA-PET/CT SUVmax of the prostate gland and D’Amico classification, ISUP grade, PSA value, and status of metastasis. They also analyzed the usefulness of PSA and Ga68 PSMA-PET/CT SUVmax of the prostate gland as a predictive value for diagnosing metastasis. The interesting findings of this study are that Ga68 PSMA-PET/CT SUVmax of the prostate gland is correlated with metastasis. However, the authors did not discuss why Ga68 PSMA-PET/CT SUVmax of the prostate gland correlated with metastasis. They should more deeply discuss this question according to biological aspects.
Answer 1: The correlation of the SUVmax value of the prostate gland with metastasis was discussed.
Comments 2: The introduction should be more comprehensive. The authors should add some description of the D’Amico and ISUP classifications, how they are used, and the problems that should be overcome.
Answer 2: The introduction was written more comprehensively. D'Amico and ISUP risk classifications were explained.
Comments 3: D’Amico classification was developed for localized prostate cancer patients who received radical treatment and it classified them into low, intermediate and high risk according to recurrent risk. Thus, it is not accurate to classify prostate cancer patients with metastasis.
Answer 3: You are right not to use the D’Amico risk classification in patients with metastatic prostate cancer. However, these patients were diagnosed with an unknown metastasis. Metastasis was diagnosed with Ga68 PSMA PET/CT. We wanted to emphasise that the higher the risk class in the clinical classification, the higher the probability of metastasis.
Comments 4: The following sentence does not make sense. “While 97% of high-risk patients had metastasis, 51% did not. Metastasis was present in 7% of 98 medium-risk patients, while it was absent in 93%. Metastasis was present in 6% of low-risk patients, but not in 94%.
Answer 4: Table 1 was revised and the percentages were corrected.
Comments 5: Damico should be D’Amico.
Answer 5: Damico was corrected to D’Amico
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsPlease add the answers to the comments in the paper. Readers should be aware of the fact that GS 3+3 PC with metastasis were not re-biopsied (and thereforme confirmed GS 3+3) and that metastasis were confirmed by additional imaging
Author Response
Comments 1: Please add the answers to the comments in the paper. Readers should be aware of the fact that GS 3+3 PC with metastasis were not re-biopsied (and thereforme confirmed GS 3+3) and that metastasis were confirmed by additional imaging
Response 1: Biopsies were not repeated in patients with metastatic Gleason score 3+3 prostate cancer. However, suspicious metastases were confirmed through additional radiological imaging.
Added to the Materials and Methods section.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe Discussion has not been improved following the references suggested.
Author Response
Comment 1: The discussion has not been improved following the references suggested.
Response 1: Added to discussion with suggested reference.
Round 3
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript has been improved
