Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Review Report

1.Brief Summary:

This study aims to investigate the prognostic factors of locally advanced squamous cell carcinoma of the skin (LASCC) in transplant recipients. Through a retrospective analysis of clinical data from patients between 2009 and 2025, the study found that transplant recipients (immunosuppressed patients) had significantly higher recurrence and mortality rates compared to non-transplant patients, with lower survival rates. The study emphasizes the aggressiveness of LASCC in transplant recipients and highlights the need for more precise treatment guidelines for this specific population. This research provides important data for understanding the prognostic differences of LASCC in transplant recipients and offers direction for future research and clinical practice.

2.Comments on General Concepts:

1)Research Purpose and Contribution: The study focuses on the prognostic factors of LASCC in transplant recipients, which is of significant clinical importance. With the increasing number of organ transplants, the incidence and aggressiveness of skin cancer in transplant recipients have become increasingly prominent. This study provides new data and insights in this field.

2)Hypothesis and Testability: The study hypothesizes that due to their immunosuppressed state, transplant recipients have a worse prognosis for LASCC. This hypothesis is highly testable. By comparing the recurrence rates, mortality rates, and survival rates between transplant and non-transplant patients, the hypothesis can be effectively validated.

3)Accuracy of Methodology: The study employs a retrospective single-center research design, which can provide certain data support but may be subject to selection bias. It is suggested that the limitations of this study design be mentioned in the discussion section, and possible sources of bias, such as patient selection and differences in treatment plans, be explored.

3.Comments on Specific Aspects:

1)Completeness and Relevance of the Topic: The study topic focuses on the prognostic factors of LASCC in transplant recipients and is highly clinically relevant. However, the discussion on preventive and early intervention measures for skin cancer in transplant recipients is relatively limited. It is suggested that relevant content be added in the discussion section to explore how to reduce the incidence and aggressiveness of skin cancer in transplant recipients through optimizing immunosuppression protocols or enhancing skin monitoring.

2)Appropriateness of References: The manuscript cites a large number of relevant references, but some of the cited references are relatively old. It is recommended to add the latest research progress within the past five years to enhance the timeliness and scientific nature of the study.

4.Specific Comments on Line Numbers, Tables, or Figures:

1)The text discusses the risk of skin cancer in transplant recipients but does not mention the specific impact of different types of immunosuppressive drugs on the risk of skin cancer. It is suggested to briefly mention the differences in the risk of skin cancer caused by various immunosuppressive drugs in the introduction section to provide background for subsequent studies.

2)The article discusses the impact of tumor staging and differentiation on prognosis but does not mention the relevant findings of other international studies. It is suggested to add comparisons with the results of other studies to highlight whether the findings of this study are consistent with international research; the basis and criteria for the selection of surgical plans are not elaborated in detail. It is suggested to add a detailed explanation of the selection of surgical plans in the discussion section, including how to choose the most suitable surgical method based on the specific circumstances of patients.

5.Overall Evaluation:

The manuscript is scientifically reliable to a certain extent, with a reasonable research design, clear data presentation, and conclusions that are basically consistent with the presented evidence. However, there are some shortcomings in the rigor of methodology and the interpretation of some data. It is suggested that the authors make revisions and improvements according to the above comments to enhance the scientific nature and readability of the manuscript.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This study investigates prognostic factors in locally advanced cutaneous squamous cell carcinoma of the head and neck among transplant recipients, a population at markedly increased risk due to immunosuppression. Conducted as a 16‑year retrospective cohort of 156 patients, including 32 transplant recipients, it analyzes clinical, pathological, and surgical outcomes. Findings reveal higher recurrence, compromised margins, extranodal extension, and distant metastasis in transplanted patients, correlating with poor survival. Multivariate analysis highlights transplantation, neck metastasis, and distant spread as key predictors of adverse outcomes. The authors emphasize the urgent need for tailored guidelines to improve management and survival in this vulnerable group.
In general, the paper is well-written and suitable for publication. However, I have some suggestions.

1. In the introduction you mention "cutaneous squamous cell carcinoma" but in the title it is "skin SCC". Please change the title to CSCC.
2. The abstract is dense, with excessive statistical detail that obscures readability. I suggest summarizing key findings more narratively, leaving detailed statistics for Results. Highlight clinical implications more clearly.
3. Methodology: There are some parts that are not clear. The definition of LASCC is complex and somewhat inconsistent (multiple criteria listed). The authors mentioned it's a case series, but I believe including 156 patients in a 16-year period is not a case series. I suggest summarizing the methodology to be more reader-friendly and avoid redundancy.
4. Results section mixes descriptive statistics with inferential outcomes, making it hard to follow. I suggest separating clearly into (a) baseline characteristics, (b) univariate analysis, (c) multivariate analysis, and (d) survival outcomes.
5. Tables are cluttered with excessive detail. Please simplify tables to highlight clinically relevant comparisons.
6. Discussion: To be more practical, please compare your study with international ones.
7. The study design is retrospective single-center, but limitations are not acknowledged. Please add a limitations paragraph before the conclusion and address your limitations.
8. Language: The manuscript contains minor grammatical inconsistencies, awkward phrasing (“best and best treatment”; Line 157) and redundancy in terms (“locally advanced SCC” repeated excessively). Use consistent abbreviations (LASCC) after the first definition.  I think professional language editing is useful for clarity and conciseness.

Author Response

 

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

This article presents a retrospective, single-center study analyzing a consecutive cohort of patients with locally advanced cutaneous squamous cell carcinoma of the head and neck treated at a single hospital. Only cases managed surgically were included, and outcomes were compared between transplant recipients and non-transplant patients. The aim was to describe clinicopathological characteristics and estimate outcomes such as overall survival and disease-free survival, as well as to explore prognostic factors, particularly in the transplanted subgroup. To this end, variables related to tumor extent, adjuvant treatments, and recurrence and mortality events were evaluated.

The manuscript has some methodological flaws and is not entirely clear in its writing. Although the topic is relevant to the field, the central idea that immunosuppression/transplantation is associated with a worse prognosis is already widely described, and the article itself frames its findings as additional to what the literature states.

Most of the cited references are recent and relevant. The manuscript includes only one self-citation.

The ethical and data availability statements are adequate.

The authors do not perform a normality study to justify using non-parametric tests (they state, "Statistical analyses used the Mann-Whitney nonparametric test for small samples; a two-proportion test to compare the proportion of two variables with the level of significance"). They use the chi-square test with a significance level of p < 0.05 for comparing percentages (frequencies). With non-significant p-values, inappropriate claims are made: "Furthermore, our results revealed a 71% prevalence of grade 2-3 histologic differentiation in LASCC, which was strongly associated with recurrence (p=0.051)" see line 346. The use of the chi-square test is incorrect in some tables, as there are tables with >25% of cells with absolute values ​​less than 5, which would require grouping the variables or using Fisher's exact test. Concepts such as odds ratio and hazard ratio are mixed (see line 297). There are too many bivariate comparisons (tables with multiple p-values) that are not adjusted for multiplicity, which increases false positives, and confounding is not controlled for when constructing the multivariate model. In general, the tables are understandable, but their clarity is only moderate: they convey the results, although the formatting and labeling make them difficult to read quickly. The descriptive and univariate tables are very long and have many rows. Furthermore, there are inconsistencies in style and naming (for example, typos such as "Lymphoma," "Radiotherapia," "Palliative") and a mix of numeric formats (comma vs. decimal point). They use location abbreviations that are not explained in the headings themselves.

The limitations of the study are not considered.

Comments on the Quality of English Language

 there are inconsistencies in style and naming (for example, typos such as "Lymphoma," "Radiotherapia," "Palliative")

Author Response

 

Please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

I have read the manuscript with the corrections suggested by this reviewer and the final version incorporating the other suggestions:

1) The suggested methodological changes have been included regarding the limitation of using the chi-square test when there are tables with >25% of cells with absolute values ​​less than 5, including Fisher's exact test where possible.

2) There are still very large tables of bivariate comparisons, although the authors justify this by stating that they are important.

3) The study limitations suggested to the authors have been included.

4) In citation 52 (Zeng S, Fu L, Zhou P, Ling H. Identifying risk factors for the prognosis of head and neck cutaneous squamous cell carcinoma: A systematic review and meta-analysis. PLoS One. 2020 Sep 29;15(9):e0239586), the authors state: “Another study by Zeng et al. found poor differentiation, perineural invasion, and Breslow thickness greater than 2 mm as associated factors.” with an increased risk of metastasis;”. They indeed transcribe the Breslow index from the published article, which refers to cutaneous squamous cell carcinoma; however, the Breslow index for tumor thickness is exclusive to melanoma and should not be used for other cutaneous tumors.
5) The manuscript has improved overall.

Author Response

 

Please see the attachment.

Author Response File: Author Response.pdf