Review for 10.1186/s12876-023-02893-2 (2023)

Title: Second primary colorectal cancer in adults: a SEER analysis of incidence and outcomes
Version: 1 Date: 30 Apr 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are major issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: My overall impression of the study is that the authors have asked a
clinically irrelevant research question and inappropriately performed the analyses. I commend
the authors on being able to base the research on the SEER dataset.
The study design of the research would cause significant confusion while reading on. From
the start, a reader will think that the second primary CRC could only occur in patients with a
prior primary CRC treated before who attained complete remission. Nevertheless, ultimately,
one will find out that the second primary CRC can occur in any patient with any cancer before.
Here, my bias is that the authors have regrettably asked a clinically irrelevant research question.
This can cause several potentially challenging issues: in patients with a history of synchronous
multifocal or multilocal breast primary or head and neck primary cancers, would the authors
regard subsequent cancer in the CRC as a second primary or not? What clinical significance
is there when a patient is diagnosed with the first primary CRC after the previous occurrence
of a different primary cancer other than CRC? If there are no shared etiologies such as prior
breast cancer caused by heritable BRCA mutation or endocrine treatment. CRCs frequently have
different etiologies than non-CRC cancer; how can readers interpret the generated results?
REQUESTED REVISIONS:
My pleasure to assess the research quality of this manuscript. The study design of the research
would cause significant confusion while reading on. From the start, a reader will think that the
second primary CRC could only occur in patients with a prior primary CRC treated before who
attained complete remission. Nevertheless, ultimately, one will find out that the second primary
CRC can occur in any patient with any cancer before. Here, my bias is that the authors have
regrettably asked a clinically irrelevant research question. This can cause several potentially
challenging issues: in patients with a history of synchronous multifocal or multilocal breast
primary or head and neck primary cancers, would the authors regard subsequent cancer in the
CRC as a second primary or not? What clinical significance is there when a patient is diagnosed
with the first primary CRC after the previous occurrence of a different primary cancer other
than CRC? If there are no shared etiologies such as prior breast cancer caused by heritable
BRCA mutation or endocrine treatment. CRCs frequently have different etiologies than non-
CRC cancer; how can readers interpret the generated results?
Lines 79 to 80: Their Chinese colleagues, Yang et al., in March 2023, published a relevant
paper in Int J Colorectal Dis (2023 Mar 30;38(1):88.), entitled, Incidence and risk outcomes
of second primary malignancy of patients with post-operative colorectal cancer. Chen et al. in
2022 published a similar paper, 'The incidence of second primary cancer in male and female
patients with initial colorectal cancer: a SEER population-based study' in Eur J Cancer Prev 2022
Sep 1;31(5):430-441. Editors would appreciate it if the authors re-perform new literature and
incorporate these articles and some other relevant papers that were not yet cited in the current
manuscript.
Line 344: The authors stated that they analyzed factors associated with the occurrence of spCRC;
however, many factors are irrelevant owing to the study design, e.g., how the tumor grade
of breast cancer would affect the occurrence of a subsequent spCRC. The factors that would
impact the occurrence of spCRC should include cigarette smoking, alcohol smoking, genomic
p53 status, and family history of colorectal cancer. However, all these essential factors were
not available.
Figure 1. There is an unrecognized word 'Patientsi" in the lower part of Figure 1.
Figure 7. The label 'Primary Site' causes confusion. Do you mean 'the first primary cancer site?'
This adds little information by itself. Suggest moving it to Supplementary Information.
With that, I would recommend that the authors re-focus their research question to spCRC after
the initial CRC was under reasonably good control, then the comparison becomes clinically
relevant. Second, the author could ask the research question that what do spCRC look like in
patients who had a primary gastrointestinal tract cancer other than CRC. Getting rid of those
first primary cancers that share no common etiology with the subsequent spCRC is also strongly
recommended, this practice will markedly reduce the heterogeneity of your study population
and make interpretation possible.