Comparison of Prognostic Factors for Merkel Cell Carcinoma, Mucosal Melanoma and Cutaneous Malignant Melanoma: Insights into Their Etiologies

Round 1

Reviewer 1 Report

In this paper, it was described mucosal melanoma (MM) and Merkel cell carcinoma (MCC) in comparison to cutaneous malignant melanoma (CMM) regarding rates and prognostic factors to better understand their etiology. The manuscript needs major revision.
Comments:
1. In this type of article, the word "gender" is better than the word "sex", which is suggested to be replaced.

2. The English language of the manuscript has many errors and should be thoroughly checked. The tense of the verbs is wrong in different parts of the manuscript, which it should be corrected.

3. Today, analytical approaches are used in the diagnosis of melanoma, which can be written about in this manuscript, and there are useful resources in this case, for example:
DOI: 10.1016/j.trac.2019.05.004
DOI: 10.1088/1742-6596/1362/1/012011
DOI: 10.1016/j.bios.2018.10.018

4. The title needs to be improved and corrected and it can be written more comprehensively and concisely.

5. In figure 1, the y-axis is not written in the graph.

6. The discussion is divided into several parts, which is not usual at all, and each part has a lot of additional content. It is better to integrate and summarize the discussion. The introduction is short and some of the discussion content can be transferred to the introduction.

7. It is suggested to draw a figure that shows the prevalence of each of the cancers studied in this study in the studied geographical areas.

Author Response

Reviewer #1

In this paper, it was described mucosal melanoma (MM) and Merkel cell carcinoma (MCC) in comparison to cutaneous malignant melanoma (CMM) regarding rates and prognostic factors to better understand their etiology. The manuscript needs major revision.
Comments:
1. In this type of article, the word "gender" is better than the word "sex", which is suggested to be replaced.

Thank you for your suggestion.  However, the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program’s data report on biological sex not gender. To be consistent with how the data are collected and all publications using SEER data, we have not changed SEER’s label.

2. The English language of the manuscript has many errors and should be thoroughly checked. The tense of the verbs is wrong in different parts of the manuscript, which it should be corrected.

Based on the reviewers’ comments, we have proofread and edited the manuscript including verb tense throughout.

3. Today, analytical approaches are used in the diagnosis of melanoma, which can be written about in this manuscript, and there are useful resources in this case, for example:

Thank you for these references. We added the references by Eftekhari et al., 2019 as it is relevant to our discussion of standard options for clinical care for those not familiar with these cancers. We feel the other two publications are too technical with respect to how melanoma might be detected and beyond the level for this manuscript.

4. The title needs to be improved and corrected and it can be written more comprehensively and concisely.

We have changed the title to “Comparison of prognostic factors for Merkel cell carcinoma and mucosal melanoma to cutaneous malignant melanoma:  insights to etiology”. 

5. In figure 1, the y-axis is not written in the graph.
   
   

We added labels for the percentage change and calendar year of diagnosis to Figure 1.

6. The discussion is divided into several parts, which is not usual at all, and each part has a lot of additional content. It is better to integrate and summarize the discussion. The introduction is short and some of the discussion content can be transferred to the introduction.
   
   

We recognize that different disciplines and different journals have varying standards. Current Oncology does allow and often have subheadings in the discussion. Since we are comparing three different cancers, it is helpful to include these subheadings.

We did remove the subheadings cancer symptoms, standard detection and treatment.  And per the reviewer’s comments moved some of this text into the introduction.  Other aspects related to differences in our findings remain in the discussion section.

7. It is suggested to draw a figure that shows the prevalence of each of the cancers studied in this study in the studied geographical areas.

Per the reviewer’s suggestion, we added Figure 2 to map differences in the expected and observed percentage of (a) cutaneous malignant melanoma (CMM), (b) Merkel cell carcinoma (MCC) and (c) mucosal melanoma (MM) for the 16 states made up from 22 SEER 2000-2019 cancer registries.

Reviewer 2 Report

This article compares the incidence and survival rates of CMM, MCC and MM, as well as their relationships with age, sex, race, location, and stage, which is of some significance.

Here are some suggestions:

1.    In Figure 1, the variation in MM appears more pronounced than in CMM and MCC since MM has a low incidence. Consider improving by incorporating a relative change index.

2.    Add curve charts to better illustrate the relationship between survival/incidence rates and age/sex.

3.    Better to include tumor thickness and anatomic level of invasion in Table 3, as these are essential prognostic factors. It may explain why MM patients who are not staged have a higher survival percentage. 

Author Response

Reviewer #2

This article compares the incidence and survival rates of CMM, MCC and MM, as well as their relationships with age, sex, race, location, and stage, which is of some significance.

Here are some suggestions:

1. In Figure 1, the variation in MM appears more pronounced than in CMM and MCC since MM has a low incidence. Consider improving by incorporating a relative change index.

We changed Figure 1 to present separate graphs for each cancer so we can present trends by calculating annual percent change (APC) using Joinpoint Regression Program provided by the National Cancer Institute for the SEER data.

2. Add curve charts to better illustrate the relationship between survival/incidence rates and age/sex.

We have added Figure 3 presenting relative survival by age and sex but had to combine males and females for MM due to the low number of overall cases.

We did not graph incidence rates for the three cancers by age and sex since the rates per 1,000,000 population were 203.7 for CMM compared to 0.1 for MM making MM not visible when plotting CMM.

3. Better to include tumor thickness and anatomic level of invasion in Table 3, as these are essential prognostic factors. It may explain why MM patients who are not staged have a higher survival percentage. 

The anatomic level of invasion for melanoma is typically measured using Breslow Depth (tumor thickness) and Clark Level which measures the depth of invasion. We add Breslow Depth. Since Breslow Depth was only available for the SEER -17 registries, we added it to Table 4 which is restricted to SEER-17. Clark’s Level (1-5) has been collected by SEER in the past. However, now that the public use SEER data is only available through SEER*Stat rather all the data, it is not available.

Round 2

Reviewer 1 Report

All corrections have been made and the manuscript is acceptable.