Major Advances in Gynecologic Oncology in 2025: Systematic Review and Synthesis of Conference and Published Evidence

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors present a review of practise changing randomized trials in the field  of gynecologic oncology published in 2025 and/or presented at the ESMO and ASCO congresses. The methods are clearly described, the results and conclusions follow the methodology. The language is understandable. 

Author Response

We sincerely thank the Reviewer for their positive assessment of our manuscript. We are pleased that they found the methodology clearly described, the results and conclusions consistent, and the language understandable. We appreciate their recognition of our work to synthesize practice-changing trials in gynecologic oncology from 2025.

Thank you for your time and valuable feedback.

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript provides a comprehensive and timely systematic review of the transformative clinical data emerging in 2025. By synthesizing results from major conferences (ASCO 2025, ESMO 2025) and high-impact publications, the author offers a "watershed" overview of the new standards of care in gynecologic oncology. The adherence to PRISMA 2020 guidelines and prospective registration on PROSPERO (CRD420251270085) ensures high methodological rigor.

• Cervical Cancer: The author correctly identifies the final analysis of KEYNOTE-A18 as a practice-changing milestone, establishing pembrolizumab plus chemoradiotherapy as a new global standard for high-risk locally advanced disease. Additionally, the inclusion of the PHENIX trial validates sentinel lymph node biopsy (SLNB) as a safe surgical de-escalation strategy, which is critical for reducing patient morbidity.

• Ovarian Cancer: The synthesis of the ENGOT-ov65/KEYNOTE-B96 trial is excellent, highlighting it as the first trial to demonstrate a statistically significant overall survival (OS) improvement with an immune checkpoint inhibitor in platinum-resistant recurrent ovarian cancer (PRROC). The discussion of novel mechanisms, such as glucocorticoid receptor modulation (ROSELLA) and cadherin-6-targeted ADCs (REJOICE-Ovarian01), provides essential insights into overcoming treatment resistance.

• Endometrial Cancer: The manuscript clearly delineates the "MMR dichotomy," noting that while dMMR/MSI-H tumors see transformative survival benefits from first-line immuno-chemotherapy (RUBY, AtTEnd), the benefit for pMMR tumors remains primarily limited to progression-free survival without a clear OS advantage.

• Translational Insights: The inclusion of ctDNA dynamics (from CALLA and DUO-E) as a real-time prognostic biomarker is a sophisticated addition that looks toward the future of personalized risk stratification.

Conclusion: The manuscript is exceptionally well-organized. Tables 1 and 2 are particularly valuable for clinicians, providing a concise summary of trial designs and outcomes. The risk of bias assessment using RoB 2 adds further credibility to the synthesis.

Author Response

We sincerely thank the Reviewer for their thoughtful and positive assessment of our manuscript. We are pleased that they found our systematic review comprehensive, timely, and methodologically rigorous. We appreciate their recognition of the key advances we highlighted across cervical, ovarian, and endometrial cancers, as well as the translational insights on biomarkers. Their comments reinforce the value of this synthesis for the clinical and research communities. We have carefully considered their feedback and are grateful for their endorsement of the manuscript's organization and clarity.

Thank you again for the constructive and encouraging review.

Reviewer 3 Report

Comments and Suggestions for Authors

• The abstract is too long and difficult to follow. Perhaps the keywords should be reduced further.
• The introduction is well-documented and contains relevant information.
• The design and purpose of the study are clear. Additionally, the inclusion and exclusion criteria are relevant and concise.
• The “Materials and Methods” section is well structured as text, but it would be advisable to present the research question (PICO) in a table and to provide a visual summary of the selected studies, such as the number and year of publication. Additionally, the assessment of study quality (according to the ROB-2 domains) should be presented in a table or figure.
• The PRISMA diagram is not visualised in the manuscript, so I cannot comment on it. This is of major importance for selecting studies in a systematic review, so I hope it is clear and representative, especially since the text does not mention the number of studies obtained following the search criteria, the studies excluded, those processed, and the ones included in the review.
• A more explicit description of the number of selected studies is necessary in the Materials and Methods section (if it is a systematic review, the selection must be highly standardized) – a clear table is essential, even if the Results section begins with this informations.

 

• The tables and figures are explicit and suggestive for understanding the text.

 

• Line 354 – It is recommended to include a figure to show Risk of bias assessments for randomized controlled trials using the Cochrane Handbook Risk of Bias tools for randomized trials (RoB-2).
• The results are well-founded, but difficult to follow, which is why graphical illustrations or tables help the reader correlate the information in the text.
• The statements in the ”Discussion” chapter are coherent, but more cited references should support them. However, a more critical discussion about the limitations of the included studies, the heterogeneity of the populations, and even the accessibility of new therapies would be helpful.
• The conclusions are aligned with the results and reflect current trends, such as biomarker-guided therapies or the integration of immunotherapy at all stages of the disease. They provide a valuable framework for updating clinical guidelines, but need slight refinement.
• The cited references are few, but they are mostly recent publications and appropriate for the discussed topic. However, the reference formatting requires careful review – please follow the Journal instructions.

Author Response

 

Point-by-Point Response to Reviewer's Comments

Dear Reviewer,

We sincerely thank you for your thorough evaluation and constructive feedback, which has significantly improved our manuscript. We have carefully addressed each of your comments, as detailed below.

Comment 1: The abstract is too long and difficult to follow. Perhaps the keywords should be reduced further.

Action Taken:

• We have substantially shortened and restructured the Abstract to enhance its conciseness and readability.
• The number of keywords has been reduced, in line with the journal's recommendations.

Comment 2: The introduction is well-documented and contains relevant information.

Response: We thank you for this positive assessment. The introduction has been reviewed for consistency with the revised manuscript but required no major changes.

Comment 3: The design and purpose of the study are clear. Additionally, the inclusion and exclusion criteria are relevant and concise.

Response: We appreciate this feedback. We have maintained the clarity of this section.

Comment 4: The “Materials and Methods” section is well structured as text, but it would be advisable to present the research question (PICO) in a table and to provide a visual summary of the selected studies, such as the number and year of publication. Additionally, the assessment of study quality (according to the ROB-2 domains) should be presented in a table or figure.

Action Taken:

• PICO table:We have added Table 1 presenting the PICO framework in a structured format.
• Visual summary:We have included Table 2 (PRISMA Flow Summary) and Figure 1 (PRISMA 2020 flow diagram) to visually illustrate the study selection process.
• Quality assessment (RoB-2):We have added Figure 2 illustrating the risk of bias assessment using the RoB-2 tool for phase III RCTs, accompanied by a detailed textual description in Section 3.3.

Comment 5: The PRISMA diagram is not visualised in the manuscript, so I cannot comment on it... A more explicit description of the number of selected studies is necessary in the Materials and Methods section – a clear table is essential.

Action Taken:

• We have inserted Figure 1 (PRISMA 2020 flow diagram)in Section 2.4.2, clearly showing the number of records identified, screened, excluded, and included.
• We have added Table 2 (PRISMA Flow Summary)in Section 2.4.1, providing a clear numerical summary of the selection process.

Comment 6: The tables and figures are explicit and suggestive for understanding the text.

Response: Thank you. We have ensured this quality is maintained in the newly added figures and tables.

Comment 7: Line 354 – It is recommended to include a figure to show Risk of bias assessments for randomized controlled trials using the Cochrane Handbook Risk of Bias tools for randomized trials (RoB-2).

Action Taken: As suggested, we have added Figure 2 in Section 3.3, presenting the RoB-2 assessment for the included phase III randomized controlled trials, with an enhanced legend for clarity.

Comment 8: The results are well-founded, but difficult to follow, which is why graphical illustrations or tables help the reader correlate the information in the text.

Action Taken:

• We have added Figure 3, providing a visual synthesis of the 2025 therapeutic advances by cancer type, highlighting key trials and their clinical implications.
• We have added Table 4, summarizing the detailed outcomes (efficacy, safety, biomarker insights, clinical implications) of the major practice-changing trials.
• The Results section text has been reorganized for clearer navigation by cancer site and clinical setting.

Comment 9: The statements in the ”Discussion” chapter are coherent, but more cited references should support them. However, a more critical discussion about the limitations of the included studies, the heterogeneity of the populations, and even the accessibility of new therapies would be helpful.

Action Taken:

• We have expanded Section 4.5.2 "Critical Appraisal of Limitations"to explicitly discuss:
  • Heterogeneity of trial populations.
  • Methodological limitations (variable follow-up, interim data, publication bias).
  • Challenges regarding accessibility to biomarker testing and novel therapies across different geographic and economic settings.
• We have added numerous supporting references (now cited as [26]-[45] in the revised manuscript) throughout the Discussion.
• We have strengthened Section 4.5.3 "Accessibility and Implementation Challenges"to address economic, infrastructural, and equity barriers.

Comment 10: The conclusions are aligned with the results and reflect current trends... but need slight refinement.

Action Taken: We have revised the Conclusion section to better highlight implementation challenges and future research priorities, while maintaining close alignment with the presented results.

Comment 11: The cited references are few, but they are mostly recent publications and appropriate for the discussed topic. However, the reference formatting requires careful review – please follow the Journal instructions.

Action Taken:

• We have significantly increased the number of references (now 46) to substantiate claims throughout the manuscript, particularly in the Introduction, Discussion, and Limitations sections.
• All references have been reformatted to adhere strictly to the journal's required Vancouver/Numeric style. Each entry has been verified for author names, article title, journal, year, volume, page numbers, and DOI accuracy.

 

In summary, we have incorporated all your valuable suggestions, leading to substantial improvements in the manuscript's clarity, methodological rigor, and analytical depth. We believe the revised manuscript now fully addresses your concerns and hope you find it suitable for publication.

Sincerely,
The Authors.