Impact of Adaptive Radiation Therapy on Toxicity in Prostate Cancer: A Scoping Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thanks for the interesting review.

My comments:

What gaps exist in the present literature on ART and toxicity in prostate cancer, and how does this review address them?

How do non-MRI-guided ART toxicity rates compare to MRI-guided ART in PCa patients? And how do dedicated commercial ART systems affect or influence toxicity levels during PCa treatment? There is also an ongoing debate on this topic. If I may ask authors for their opinion, what are the toxicity outcomes for adaptive conventional fractionated radiation therapy (CFRT) versus stereotactic body radiation therapy (SBRT) in PCa?

I couldn't find the benefits and drawbacks of CT-guided versus MRI-guided ART for prostate cancer in the text. Or did I miss them somewhere?

I did not see the future perspective on the subject matter well spelled out. Could authors add their voice on what they think is the direction in this area?

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Peer Review: Adaptive Radiation Therapy and Toxicity in Prostate Cancer (biomedicines-4126138)

1. The presented study is a scoping review evaluating the impact of adaptive radiation therapy (ART) on acute and late toxicities in prostate cancer. The authors aim to compare CT-guided versus MRI-guided ART and conventional fractionated radiation therapy (CFRT) versus stereotactic body radiation therapy (SBRT). The study follows PRISMA-ScR guidelines and includes 27 studies published between 2000-2025.

2. The review found median acute toxicities of 1.0% for grade 2 gastrointestinal (GI) and 9.6% for grade 2 genitourinary (GU) toxicity. Late toxicities were 2.0% for grade 2 GI and 5.0% for grade 2 GU. Grade 3 toxicities were 0.0% for both acute and late effects in GI and GU systems. The choice of image guidance modality (CT versus MRI) did not substantially influence toxicity outcomes. Adaptive CFRT and SBRT showed comparable toxicity rates.

3. This review fills an important gap by comparing different ART modalities and fractionation schemes. The findings support clinical decision-making by demonstrating that adaptive CFRT can be used when SBRT is unsuitable without increasing toxicity risk. The review advances previous meta-analyses by including CT-guided ART and comparing multiple commercial ART systems. Results show that dedicated commercial ART systems may reduce toxicity more effectively.

4. Consider the following to improve the submission:

4.1. The wide ranges in toxicity rates (e.g., acute grade 1 GU: 1.0-100.0%) indicate substantial heterogeneity across studies. Perform sensitivity analysis excluding outlier studies to determine if conclusions remain stable. Subgroup analysis by sample size categories would clarify whether study size influences reported toxicity rates.

4.2. Provide a supplementary table documenting missing data patterns for each included study. This would identify which parameters (TNM staging, hormonal therapy proportion, rectal spacer use) are most frequently unreported.

4.3. Include timeline figures showing when different ART systems were introduced and adopted across studies. This would contextualize why CT-guided studies are older (2005-2018) while MRI-guided studies are recent (2019-2025).

4.4. Table 2 does not extract follow-up duration, yet late toxicity assessment requires minimum observation periods. Provide median follow-up time and clarifying minimum follow-up thresholds. This could explain variations in late toxicity reporting completeness.

4.5. While quality assessment is optional for scoping reviews, applying standardized checklists would strengthen evidence synthesis. The Joanna Briggs Institute tools are appropriate for the prospective and retrospective cohort designs represented. Report quality scores in supplementary materials.

5. The conclusions are consistent with the evidence provided. The authors appropriately note that only one study evaluated the Radixact Synchrony CT-guided system. The call for more research on CBCT-guided ART is justified given the absence of identified studies. The comparison with Leeman et al.'s meta-analysis strengthens confidence in the findings.

6. Regarding tabular and illustrative data:

6.1. Table 1 presents inclusion and exclusion criteria. Table 2 presents study characteristics across 27 papers. Table 3 shows toxicity rates stratified by modality and grade.

6.2. The PRISMA flow diagram (Figure 1) is complete and follows standard reporting. Wide ranges in toxicity rates are appropriately presented.

7. The authors state no new data were created, and data sharing is not applicable. Ethics approval was not required for this review. The study was registered with Open Science Framework (DOI: 10.17605/OSF.IO/U9Y7G), demonstrating transparency.

8. The review adheres to PRISMA-ScR checklist requirements. Funding disclosure is transparent. No conflicts of interest are declared. The review would benefit from meta-regression analysis if sufficient homogeneous data were available.

This scoping review demonstrates PRISMA-ScR adherence, pre-registration, and evidence synthesis across 27 studies. Substantial heterogeneity, wide toxicity ranges, English-language restriction, and absence of quality assessment limit evidence strength. The review successfully maps current knowledge, and may be further improved.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Using an ad hoc scoring system (2/1/0, fully/partially addressed or unaddressed), authors scored 2+2+1+2+2=9 points out of 10. Additions include sensitivity analyses (Table B1), JBI quality assessment (mean 80.8%), missing data quantification, and follow-up clarification. Timeline information integrated as text rather than figures. The manuscript has been significantly enhanced.