Self-Reported Reasons for Inconsistent Participation in Colorectal Cancer Screening Using FIT in Flanders, Belgium
Round 1
Reviewer 1 Report
Very interesting paper. I would suggest to put the results more in context of the current literature. Do the authors think that some outreach methods to increase the uptake of the screening would be useful? There's plenty of American studies on that with discordant results (for example use of financial incentives).
The authors should cite some studies on the efficacy of colonoscopy (alone or with some add-on devices) in CRC screening (cite PMID: 29133257 and PMID: 27005802)
Author Response
Please see the attachment
Author Response File: 
Author Response.pdf
Reviewer 2 Report
In this study, the authors reported the main reasons for inconsistent participation in FIT screening for CRC in Flanders. The findings may guide tailored interventions to increase FIT screening uptake in the region. The manuscript is straightforward, well written, and concise. Definitely deserves to be published and is a valuable contribution to the “Gastrointestinal Disorders” journal. Some comments need to be addressed before publication.
[1] “1. Introduction”, Lines 40-41:
“These results highlight the clinical importance of participation in CRC screening and screening adherence.”.
At that point, the authors should highlight that establishing a biomarker and molecular profile of the tumor is essential for choosing therapies that can effectively target the patient’s individual tumor mutations. The recommended colon cancer screening for defective DNA mismatch repair includes immunohistochemistry and/or microsatellite instability test.
Recommended reference: Adeleke S, et al. Microsatellite instability testing in colorectal patients with Lynch syndrome: lessons learned from a case report and how to avoid such pitfalls. Per Med. 2022;19(4):277-286.
[2] “Table 2”, Page 4, Line 144:
“Melanoma is a skin cancer originating from melanocytes and is the most deadly skin malignancy 1, 2.”.
It would be interesting if the authors are able to add the valiable “religion” in table 2. If that cannot be done retrospectively, then a comment would be made on the discussion - potentially on the limitations of the study.
Author Response
General remark of reviewer: In this study, the authors reported the main reasons for inconsistent participation in FIT screening for CRC in Flanders. The findings may guide tailored interventions to increase FIT screening uptake in the region. The manuscript is straightforward, well written, and concise. Definitely deserves to be published and is a valuable contribution to the “Gastrointestinal Disorders” journal. Some comments need to be addressed before publication.
Answer: We thank the Reviewer for the very positive evaluation and constructive comments on our manuscript.
Comment 1: Introduction”, Lines 40-41: “These results highlight the clinical importance of participation in CRC screening and screening adherence.”.
At that point, the authors should highlight that establishing a biomarker and molecular profile of the tumor is essential for choosing therapies that can effectively target the patient’s individual tumor mutations. The recommended colon cancer screening for defective DNA mismatch repair includes immunohistochemistry and/or microsatellite instability test.
Recommended reference: Adeleke S, et al. Microsatellite instability testing in colorectal patients with Lynch syndrome: lessons learned from a case report and how to avoid such pitfalls. Per Med. 2022;19(4):277-286.
Answer: We thank the reviewer for the suggestion. We have read the very interesting case report of Adeleke et al. 2022. The case report is about one case of a 40-year-old patient with a background of Lynch syndrome and metastatic carcinoma. The patient already had rectal adenocarcinoma at 22 years of age, was treated with chemoradiotherapy, and had family history of CRC. With an initial negative IHC (immunohistochemistry) test, the patient was treated with standard chemotherapy. However, a PCR-CE (PCR with capillary electrophoresis) afterwards returned a result of MSI (Microsatellite instability). The case report confirms that a specific germline mutation can give varying IHC results in Lynch syndrome, and advocates for upfront testing of mCRC using both IHC and MSI-PCR when directing therapy [1].
We find this case report in specific, and the recent growth and innovation in molecular testing and next generation sequencing technologies including liquid biopsies in CRC patients in general very interesting and promising in the field of CRC screening. However, we had difficulties incorporating this point in our study for two reasons: 1) The main focus of our study is on reasons for (re)starting or skipping FIT screening among irregular participants. 2) The population-based CRC screening in Flanders aims at prevention. Our target population for FIT screening includes individuals aged 50-74 years who do not have an increased risk of CRC, do not have any symptoms or complaints, do not have first degree family history of CRC, do not have any genetic risk factors, and did not have a colonoscopy in the past 10 years or virtual colonoscopy in the past 4 years. In fact, the case described in the suggested report would not belong to our target population for CRC screening but to the population with an increased risk of CRC who would need to follow a specific pathway instead of the general population-based screening program.
We found it difficult to align the theme ‘molecular profiles to choose therapies for tumor mutations’ with our introduction in particular or our manuscript as a whole. Therefore, we have decided not to add details on biomarker and molecular profile of the tumor to the current manuscript but will note the suggested reference for our future work.
Comment 2: “Table 2”, Page 4, Line 144: “Melanoma is a skin cancer originating from melanocytes and is the most deadly skin malignancy 1, 2.”.
It would be interesting if the authors are able to add the variable “religion” in table 2. If that cannot be done retrospectively, then a comment would be made on the discussion - potentially on the limitations of the study.
Anwer: We assume that there might be a small error in the comment regarding the sentence about ‘melanoma’ which is completely not related to our current study. Our line 144 in the Results section (above Table 2) is the following: “Almost 87% of the respondents were in a fair or good financial situation (neutral/easy/very easy) and 89% did not have to suspend a medical appointment or medical procedure due to financial problems.” And our table 2 is about ‘Sociodemographic characteristics of the survey respondents (absolute numbers and unweighted percentages)’. However, we hope that we have understood the overall comment of the reviewer correctly and revised our manuscript satisfactorily.
Indeed, in the first part of our survey, we included several questions about respondents’ general sociodemographic characteristics (e.g., sex, age, nationality at birth, language spoken at home, etc.). However, we did not ask the respondents about their specific religion due to the sensitiveness of the topic. Nevertheless, ‘religion’ was included in our fixed statements regarding reasons to participate or not to participate in FIT screening so that the respondents could select this option when it applied to their case. Apparently, the respondents could also state ‘religion’ as a facilitator or barrier to their participation in FIT screening in their open answers.
In our final results, only 19/3,401 (0.6%) delayed entrees and 8/1,927 (0.4%) dropouts indicated ‘religion’ as their reason not to participate in FIT screening (fixed statement) while 44/3,401 (1.3%) delayed entrees filled in ‘religion’ as their reason to participate in FIT screening (open answer). Due to the low numbers of respondents selecting ‘religion’ for their answer, it was not included in our main results. This finding shows that religion is only a minor factor to facilitate or prevent FIT screening in Flanders.
However, we agree with the reviewer that adding some discussion on the theme ‘religion’ will improve our manuscript. For this, we have added three references in our Discussion: a systematic review that included 21 studies about factors affecting patient adherence to CRC screening indicated that ‘religion’ acted as a barrier of CRC screening: “Believing that cancer is the will of God” [2]. A German study among 40+ year-olds indicated a link between a higher frequency of attendance in religious services and an increased likelihood of participating in cancer screenings [3]. Semi-structured interviews among 55–74-year-olds' (n=50, London, UK) indicated that religion encouraged CRC screening participation, but acts as a barrier as well [4].
Thus, we have now added this information to the Discussions of our manuscript as follows (See line 260-266):
Similarly, religion acts as both a facilitator and a barrier to CRC screening [28-30]. In our study, only 19/3,401 (0.6%) delayed entrees and 8/1,927 (0.4%) dropouts indicated religion as their reason not to participate in FIT screening (fixed statement). At the same time, 44/3,401 (1.3%) delayed entrees filled in religion as their reason to participate in FIT screening (open answer). The low percentages of respondents selecting ‘religion’ show that religion is only a minor factor to facilitate or prevent FIT screening in Flanders. As a result, it was not included in our main results.
Finally, we would like to add that the English language of our entire manuscript has been carefully reviewed by a qualified professional as well.
Once again, we thank the Reviewer for the evaluation and constructive comments and feedback on our manuscript.
References
[1] Adeleke S, Haslam A, Choy A, Diaz-Cano S, Galante JR, Mikropoulos C, Boussios S. Microsatellite instability testing in colorectal patients with Lynch syndrome: lessons learned from a case report and how to avoid such pitfalls. Per Med. 2022 Jul;19(4):277-286. doi: 10.2217/pme-2021-0128. Epub 2022 Jun 16. PMID: 35708161.
[2] Dressler, J., Johnsen, A. T., Madsen, L., Rasmussen, M., & Joergensen, L. N. (2021). Factors affecting patient adherence to publicly funded colorectal cancer screening programmes: a systematic review. Public Health, 190,67-74. https://doi.org/10.1016/j.puhe.2020.10.025
[3] Kretzler B, König H-H and Hajek A (2020) Religious Attendance and Cancer Screening Behavior.Front. Oncol. 10:583925.doi: 10.3389/fonc.2020.583925
[4] Dharni N, Armstrong D, Chung-Faye G, Wright AJ. Factors influencing participation in colorectal cancer screening-a qualitative study in an ethnic and socio-economically diverse innercity population. Health Expect. 2017 Aug;20(4):608-617. doi: 10.1111/hex.12489. Epub 2016 Aug 22. PMID: 27550367; PMCID: PMC5513014.
Author Response File: Author Response.pdf
Reviewer 3 Report
The idea is general is unique and well presented, Few comments;
1- The results need diagrams to make it simple and to give better outlook for your outcomes
2- English language need review, Please review it one more time for minor issues
3- You used 11 out of 32 of citations >2019 which is a good indicator, Keep using recent citations at least >1/3 of the total number.
Author Response
Please see attachment
Author Response File: Author Response.pdf
Reviewer 4 Report
gastrointestdisord-2029593
Drs. Sarah Hoeck and Thuy Ngan Tran report the main reasons for inconsistent participation in FIT screening for CRC in Flanders, where the uptake in the population-based CRC screening program, using fecal immunochemical test (FIT) is less than 50%. They found that the most common reasons for participation were related to the importance of (preventive) health checks. The findings are of interest, but following points should be reconsidered.
(1) Words “GPs” and “andmedia” should be specified.
(2) “Discussion” is too long. Please shorten.
(3) “Conclusion” must be concise.
(4) Finally, methodology and some data can be present in figure(s). Is this possible?
Author Response
See in attachment
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The manuscript is OK now
Reviewer 4 Report
This paper contains some interesting findings regarding the main reason for inconsistent participation in FTT screening for CRC in Flanders. Revision is adequate and it is now acceptable in the journal.
