Quantification of Equivocal Findings in F18-Fluciclovine PET/CT Scans for Biochemical Recurrence of Localized Prostate Cancer

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study investigates the level of uncertainty in PET/CT reporting for patients experiencing biochemical recurrence of prostate cancer who underwent PET/CT with fluciclovine. The paper presents intriguing findings, demonstrating a correlation between higher levels of uncertainty in PET/CT reporting and the anatomical location of lesions as well as PSA levels.

However, there are a few minor concerns:

When the authors first mention fluciclovine as an alternative tracer to FDG for prostate cancer, it is important not to overlook citing the following relevant papers: Lewal et al. (doi: 10.1097/RLU.0000000000004590) and Filippi L et al. (doi: 10.1080/17434440.2022.2117612).

In the materials and methods section, specifically in lines 81-82, please provide a definition of biochemical recurrence or specify the criteria used to determine BCR.

In the discussion section, the authors discuss PI-RADS and PSMA-RADS as approaches to categorize imaging findings on MRI and PSMA PET, with the latter overshadowing fluciclovine PET in recent years. However, it should be noted that PSMA-RADS has primarily been used for describing patients at staging/diagnosis, whereas fluciclovine PET has been utilized in cases of biochemical recurrence. Therefore, I suggest the authors mention the PROMISE approach, a categorization method initially introduced for PSMA but adapted to fluciclovine by some authors (Salvati et al. DOI: 10.1007/s00259-021-05415-y).

Author Response

I would like to thank the reviewer for thier critical analysis and excellent suggestions.

 

• I have added the references suggested  (Lewal et al. (doi: 10.1097/RLU.0000000000004590) and Filippi L et al. (doi: 10.1080/17434440.2022.2117612).
• I have specified the definition of biochemical failure as suggested
• I have integrated the PROMISE approach intot he discussion, and included the reference as suggested.

These were excellent suggestions and strengthen the manuscript overall.

Reviewer 2 Report

Comments and Suggestions for Authors

The work of Sung et al. certainly does not represent a sensational scientific discovery, but it describes a fundamental even if daily activity of the radiologist such as that of reporting. The reporting itself represents the final act of the diagnosis and the words used are fundamental to communicate to the clinician the presence and severity of the disease. The work was conducted on a widespread pathology such as disease recurrence in prostate cancer and the tables were rightly divided based on the disease sites and the increase in the PSA level. I find the article very interesting, worthy of being published because it must make us reflect on the words that are used in radiological and nuclear medical reports.

Author Response

We appreciate the favorable review.  There were no specific changes to address from this reviewer.

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript is interesting but some points should be improved

1. PSMA PET/CT has been proposed to perform targeted biopsy in men with clinical suspicious of prostate cancer (Pepe P, Pepe L, Cosentino S, Ippolito M, Pennisi M, Fraggetta F. Detection Rate of 68Ga-PSMA PET/CT vs. mpMRI Targeted Biopsy for Clinically Significant Prostate Cancer. Anticancer Res. 2022 Jun;42(6):3011-3015). The Authors should report the relevance to indicate the target prostatic zones suspicious for PCa 

2. The Authors should discuss the relevance to report the intraprostatic SUVmax to diagnose clinically significant PCa 

3. The Authors should improve references adding papers that compare the accuracy PSMA PET/CT vs CT and bone scan in PCa staging and in the diagnosis of PSA recurrence

4.The Authors should report the false negative rate of PSMA PET/CT in PCa staging

Comments on the Quality of English Language

Minor Editing of English language is required

Author Response

We appreciate this author's review.  Although the reviewer brings up excellent points about the parallels of  PSMA PET/CT in the diagnosis and staging of prostate cancers and how they may be relevant to this study focusing on imaging reports from fluciclovine scans

1. We have considered the reviewer's comments and included the necessary context and reference in the discussion section. This is addressed in the paragraph that delves into the topic of PSMA PET/CT.

2-4. Comments 2-4 are particular to the nuances of PSMA pet/ct, specifically in the diagnosis or staging arena.  Since this paper does not focus on the pre-pathologic diagnostic utility of PSMA PET/CT scan arena, the authors feel that including the suggestions in comments 2-3 may confuse the reader by being beyond the scope.  Comment 4 is also felt to be beyond the scope of this manuscript because the topic and interpretation of false negative rates on PSMA PEt/Ct is non-contextual to that of fluciclovine scans

Reviewer 4 Report

Comments and Suggestions for Authors

Manuscript ‘Quantification of equivocal findings in PET/CTscans for biochemical recurrence of localized prostate cancer’ by Sung et al.

 

This paper describes the findings of a merely descriptive study in which the authors assess varying language utilized in the radiology reports of F18-fluciclovine PET/CT. The percentage of definitive findings, either positive or negative is highest in bone and lowest in prostate after RT. The main problem is the subjectivity of the unsure findings, e.g. when terms as ‘suspicious for’, ‘conspicious’ and ‘compatible with’ are being used. This limitation is recognized by the authors at the end of the discussion section and should be more elaborated, also in relation to the Likert scale mentioned in the paragraph about PSMA-RADS that could potentially be of help in a semiquantitative way. In addition this reviewer has the following concerns:

 

 

 

Major:

1)    Results. The percentages for definitive language in the text do not correspond to table 2 right away. The reader needs to add up the definitive positive and negative findings from table 2 for all patient scans, which is somewhat inconvenient. The other percentages mentioned in the text do not seem to correspond at all. Maybe an all regions column should be added to table 2?

2)    Results. In table 2 a maximum total number of 295 patient scans is mentioned. How does this compare to the final analysis set of 353 reports mentioned in the materials and methods section?

 

Minor:

1)    Please use consistent nomenclature throughout the paper, e.g. F18-fluciclovine PET/CT. F-PET/CT is not appropriate, because F usually involves fluorine.

Author Response

We appreciate the reviewer's thoughtful comments

Concerning major concerns:

1) An "all regions" column cannot be accurately represented because reports were heterogeneous in reporting on all the specific anatomic subsites. For example, by definition, "prostate" and "fossa" are mutually exclusive.  Additionally, out of 353 scans, only 295 radiologists reported anything on bone, whereas 58 mentioned nothing regarding that site.  As such, the table is arrayed to represent the actual information that can be accounted for and characterized as a percentage of findings. Including "missingness" in the calculations would skew the interpretation of positivity or negativity.

2. We have added a note to the Table 2 description that explains why the numbers do not sum to 353

 

Minor:

We have made the correction as requested by the reviewer

Reviewer 5 Report

Comments and Suggestions for Authors

Although the topic is interesting  and the manuscript is well written , the paper lacks of  appropriate study design and it can be considered more a letter to editor or a short communicaton rather than a presentation of scientific data in the present form

Author Response

We appreciate the reviewer's comments.  The comment was directed toward the editorial staff, and there were no specific changes to address.

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript has been improved

Author Response

No specific comments to address.

Reviewer 4 Report

Comments and Suggestions for Authors

Manuscript ‘Quantification of equivocal findings in PET/CTscans for biochemical recurrence of localized prostate cancer’ by Sung et al.

 

This paper describes the findings of a merely descriptive study in which the authors assess varying language utilized in the radiology reports of F18-fluciclovine PET/CT. The percentage of definitive findings, either positive or negative is highest in bone and lowest in prostate after RT. The revised paper has improved, and the authors have better highlighted the importance of structured reporting by mentioning not only literature references on PSMA-RADS structured reporting but also on the PROMISE structured reporting guideline.

This reviewer still has the following concerns:

 

 

 

Major:

1)    Results. The percentages for definitive language in the text still do not correspond to table 2 right away. The reader needs to add up the definitive positive and negative findings from table 2 for all patient scans, which is inconvenient. Please add ‘’both positive and negative” to line 112. The other percentages mentioned in the text still do not correspond at all, and the authors do not want to add an all regions column to table 2. See lines 120, 122 and 123. This should be changed one way or another.

 

Minor:

1)    Please use consistent nomenclature throughout the paper, e.g. F18-fluciclovine PET/CT. It is still not consistent, e.g. in simple summary and abstract F18 is left out.

2)    Please rephrase line 106 of the results section and  line154 of the discussion section in proper English, thank you.

Comments on the Quality of English Language

    Please rephrase line 106 of the results section and  line154 of the discussion section in proper English, thank you.

Author Response

Thank you again for this reviewers careful attention to detail and clarity.

Major: 

1) We have updated the results section to clarify the probability of entirely negative scans (stratified by prescan PSA) and have clarified that "any" definitive language is the combination of positive or negative findings.  We have updated table 2 as suggested, by including rows that account for "Defitinitve Language, positive or negative", so that the reader does nothave to do this manually. Finally, as requested, we added an "Any Region" column to the table.

Minor:

1) we have updated the nomenclature throughout the manuscript as requested

2) we attempted to rephrase the specified sentences to improve readability

 

Many thanks to this reviewer for these excellent suggestions.

Round 3

Reviewer 4 Report

Comments and Suggestions for Authors

The paper has improved once more. No further comments.