Identification of Early Biochemical Recurrence Predictors in High-Risk Prostate Cancer Patients Treated with Carbon-Ion Radiotherapy and Androgen Deprivation Therapy

Round 1

Reviewer 1 Report

Authors reviewed retrospectively a series of patients submitted to CIRT plus ADT for high-risk PC. The topic is original. Reporta about carbon - ion radiotherapy is a novel radiotherapy technique. Authors examined an homogenus population of a prospective databe.

Authors found that cT3b and %75PC were independent predictors of early recurrence. Overall, the paper is well written, clear and concise. Methodology is correct. Results are coherent with high volume disease (cT3b and %75PC) linked to high risk of recurrence. However, no mention of MpMRI (also before biopsy) to assess tumour volume/extension has been reported. The topic should be discussed and added to study limitations.

The main issue regarding the paper is the lack of proper staging. Beyond PET PSMA, that has only recently introduced in clinical practice, choline PET was yet available in the last decade as well as MpMRI. Probably, such investigations were out of protocol and, taking them into account would have eventually limited the numerosity of the population. Authors should discuss this topic.

Author Response

Response to Reviewer 1’s comments:

Thank you so much for your precious comments. As Reviewer 1 pointed out, a part of our patients did not undergo Mp-MRI. Also, intraprostatic gross tumor volume was not calculated using MRI in each patient. We added this point to study limitations.

Certainly, we did not assess TNM stage using PSMA-PET or choline PET. As described in Materials and Methods, we determined TNM stage using ultrasound, CT, MRI, and bone scanning as conventional modalities. We added this point to study limitations.

Reviewer 2 Report

This study aimed to identify clinical predictors of early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). I read with great interest of this manuscript and think this study bears great clinical relavance. This manuscript was also well written. However, it is remained unclear whether magnetic resonance imaging–guided focal boost to intraprostatic lesions by CIRT can further improve outcomes in your high-risk patient. It is also unclear whether biology guided boost to PSMA-avid subvolume in the prostate region is feasible in your setting (Clin Transl Radiat Oncol. 2022 May 17;35:84-89). Evidence had reported focal boost to intraprostatic lesions was feasible and safe, with low toxicities and favorable biochemical disease outcomes (doi.org/10.1016/j.euo.2022.10.001). Could you please comment on it?

Fair.

Author Response

Response to Reviewer 2’s comments:

 Thank you so much for your precious comments. As Reviewer 2 pointed out, MRI-guided or biology-guided focal boost therapies to intraprostatic lesions are very important for future directions. This study focused on the combined systematic treatments, including abiraterone, but we have also added a comment on future boost therapy.

Round 2

Reviewer 1 Report

The paper has been properly amended