Dear Dr. Cheng,

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Academic Editor

PLOS One

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: This manuscript addresses an important and timely topic in cancer survivorship, examining the long-term trajectories of health, behavioural and economic outcomes using a large nationally representative longitudinal dataset (the Health and Retirement Study, HRS). The study design, which is based on a matched cohort approach and an extended follow-up period, is a clear strength that provides valuable insights into multidimensional survivorship patterns over time. The manuscript is well structured and written in standard academic English, and the topic is clearly relevant to public health and policy.

However, there are several important methodological and analytical issues that need to be addressed. Firstly, the statistical analysis is largely descriptive and does not make full use of the longitudinal nature of the data. The absence of advanced modelling approaches, such as mixed-effects models or Generalised Estimating Equations (GEE), limits the robustness and interpretability of the findings. Secondly, although the matching strategy is appropriate, it does not account for key potential confounders such as comorbidities, socioeconomic status or baseline health conditions. This raises concerns about residual confounding. Thirdly, the observational design precludes causal inference; however, some of the interpretations in the manuscript appear to use causal language and should therefore be revised.

Additionally, key sources of bias, such as survivorship, attrition, and measurement biases related to self-reported data, are not adequately addressed in the limitations section. The lack of clinical granularity, particularly with regard to cancer type, stage and treatment modalities, further limits the applicability and interpretability of the findings. The results section would benefit from more detailed statistical reporting, including effect sizes and multivariable analyses. While the discussion is comprehensive, it includes some speculative explanations that are not directly supported by the data and should be tempered.

In terms of transparency, the data availability statement is appropriate given that the HRS dataset is publicly accessible. However, providing additional details about dataset versions and analytical procedures would strengthen reproducibility further. While the reference list is generally relevant and up to date, improvements in formatting consistency and the removal of non-academic sources are recommended.

No major concerns relating to research ethics, dual publication or publication ethics were identified. Overall, the manuscript shows strong potential, but substantial revisions are required to improve its methodological rigour, analytical depth and clarity of interpretation before it can be considered for publication.

Reviewer #2: This study uses a large, well-established longitudinal dataset to examine health trajectories before and after cancer diagnosis across multiple domains. The long follow-up period, matched-cohort design, and broad range of outcomes are notable strengths. However, several methodological and interpretive concerns should be addressed before the manuscript is suitable for publication.

Major Concerns

1. The reported finding of better cognitive function among cancer survivors may be influenced by survivor bias. Patients with cancer who have poorer cognition may be more likely to die and leave the analysis, resulting in a progressively healthier surviving cohort over time. The comparison of cognition–mortality associations between groups does not fully address this concern. Please discuss the potential impact of differential survival on the cognitive findings and consider additional analyses (e.g. sensitivity analyses) to assess the robustness of this result. At minimum, the cognitive findings should be interpreted more cautiously and framed as hypothesis-generating.

2. A large number of repeated paired comparisons across multiple outcomes and time points without clear adjustment for multiple testing is reported. Please justify the use of paired t-tests for these repeated within-person measures, describe the assumed correlation structure, and address how multiplicity was handled to reduce the risk of false-positive findings.

3. There are several numerical inconsistencies in the Results that should be corrected for clarity. The text states that there were 5,431 incident cases, 7 with missing race/ethnicity, and 5,423 successfully matched among the remaining 5,424 cases. Please explicitly account for the one unmatched case and ensure the numbers are internally consistent throughout. In addition, the reported out-of-pocket spending difference differs slightly between the abstract ($2,383 [95% CI $1,705–$3,061]) and the Results section ($2,382 with no confidence interval reported). These values should be harmonized. Finally, Figure 3 appears to show a substantially higher peak in out-of-pocket spending at diagnosis than the reported between-group difference of approximately $2,382. Please clarify whether the reported estimate reflects an adjusted contrast while the figure displays raw values.

4. The interpretation of out-of-pocket spending would benefit from additional clarification. Because medical expenditures are reported over the prior two years, it is unclear how precisely spending can be aligned to the time of diagnosis, particularly when the primary finding appears to be a peak around t₀. In addition, decedent exit interviews may capture substantial end-of-life expenditures, which could disproportionately affect the cancer cohort and influence the observed spending gap. Please clarify how expenditures from exit interviews were incorporated into the spending trajectories and discuss the potential impact of the two-year recall window on temporal alignment of costs.

Minor Comments

1. The discussion of self-reported cancer diagnosis should acknowledge that misclassification may be influenced by cognitive status, which is particularly relevant to the cognition findings.

2. Please correct "hermetic effects" to "hormetic effects."

3. The transient decline in BMI around diagnosis may reflect cancer-related weight loss rather than behavioral changes and warrants brief discussion.

4. References 26 and 60 do not appear to be appropriate primary scientific sources and should be replaced with peer-reviewed references or removed.

5. Sensitivity analyses are referenced as available upon request. Consider including these results in the Supplementary Materials.

6. Please clarify the scoring of depressive symptoms, as the reported means are difficult to interpret from the current description.

7. The Abstract should more clearly describe the matching approach, including propensity score matching and the matching ratio.

8. Consider reporting absolute percentage point changes alongside relative increases in functional limitations.

9. The reported timing of recovery in physical activity appears inconsistent (4 years vs. 6 years) and should be reconciled throughout the manuscript.

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what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: review report.docx

Long-Term Comparative Trajectories of Health, Behavioral, and Economic Outcomes: From Pre-Diagnosis to Survivorship

PONE-D-25-60630R1

Dear Dr. Cheng,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Taiwo Opeyemi Aremu, MD, MPH, PhD

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

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Reviewer #2: (No Response)

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what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review?  For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #2: No

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