Highlights
– Among 53,769 five‑year survivors of breast, prostate, or colorectal cancer aged ≥66 years, late‑onset depression (5–10 years after diagnosis) occurred in 13.3% of breast, 11.8% of colorectal, and 8.7% of prostate cancer survivors (Taylor et al., JAMA Netw Open 2025).
– Medicare‑Medicaid dual eligibility, higher comorbidity burden, and preexisting anxiety were consistently associated with greater hazard of late‑onset depression across cohorts.
– In prostate cancer survivors, receipt of radiotherapy ± androgen deprivation therapy (ADT) was associated with higher depression risk.
Background
Depression is a common and consequential comorbidity in people with cancer. Systematic reviews and meta‑analyses show elevated prevalence of depression and anxiety in oncology settings compared with the general population, with broad implications for quality of life, functional status, adherence to surveillance, and mortality. As the population of long‑term cancer survivors grows, attention is shifting from acute treatment toxicities to late and chronic psychosocial sequelae that can emerge or persist years after diagnosis and treatment. Identifying patients at elevated risk for late‑onset depression is essential to prioritize surveillance, prevention, and integrated mental health care during the transition from cancer surveillance to routine preventive care.
Study design
The current analysis by Taylor et al. (JAMA Network Open, 2025) used linked SEER‑Medicare data (2022 linkage) to assemble a retrospective cohort of fee‑for‑service Medicare beneficiaries aged ≥66 years who were 5‑year survivors of breast, prostate, or colorectal cancer diagnosed between January 1, 2007, and December 31, 2012. Individuals with any prior diagnosis of depression were excluded. Survivors were followed from 5 to 10 years after diagnosis (through December 31, 2020) to capture incident (“late‑onset”) depression using a validated claims‑based algorithm. Exposures included sociodemographic characteristics, cancer site and stage, first‑year treatments, comorbidities in the year before diagnosis, and prior anxiety diagnoses. The authors analyzed each cancer cohort separately and used Fine‑Gray subdistribution hazard models to account for the competing risk of death.
Key findings
Population: 53,769 survivors were included: 13,265 breast, 26,979 prostate, and 13,525 colorectal cancer survivors. Mean age was 74.1 years; 61.9% were male. Racial/ethnic composition included 81.8% non‑Hispanic White, 7.3% non‑Hispanic Black, 5.0% Hispanic, 4.4% Asian/Pacific Islander, and 1.5% other/unknown.
Incidence of late‑onset depression
Five‑year risk of depression between years 5 and 10 after cancer diagnosis was highest for breast cancer survivors (13.3%), followed by colorectal (11.8%) and prostate cancer survivors (8.7%). These rates represent clinically meaningful burdens of mental health morbidity that occur long after active oncologic treatment for many patients.
Independent risk factors
Across cohorts, the following exposures were consistently and independently associated with higher subdistribution hazards for late‑onset depression:
- Medicare‑Medicaid dual eligibility: e.g., breast cancer survivors who were dual‑eligible had a substantially higher hazard (HR 1.38; 95% CI 1.22–1.57) compared with non‑dual beneficiaries. Dual eligibility acts as a proxy for socioeconomic disadvantage, higher social vulnerability, and unmet needs that influence mental health.
- Preexisting anxiety: the presence of an anxiety diagnosis in the year before cancer diagnosis was one of the strongest predictors (e.g., prostate cancer survivors: HR 2.82; 95% CI 2.47–3.22), consistent with well‑documented comorbidity between anxiety and depression and with anxiety being a marker for vulnerability to later mood disorders.
- Comorbidity burden: higher baseline comorbidity (measured by claims‑based indices) increased risk (e.g., breast cancer survivors: HR 1.33; 95% CI 1.12–1.57), consistent with a multifactorial relationship between physical health, functional status, and mood.
Other findings included age effects that varied by cohort: older age was associated with higher hazard in some comparisons (e.g., prostate survivors ≥90 vs 71–74 years: HR 1.57; 95% CI 1.10–2.24) but not in others (no significant difference for colorectal survivors in the same comparison). In prostate cancer survivors, receipt of radiotherapy with or without ADT was associated with a modestly higher risk of late‑onset depression (HR 1.22; 95% CI 1.10–1.36), suggesting treatment‑related effects (e.g., fatigue, sexual dysfunction, hormonal effects) might contribute to later mood disorders.
Risk stratification
The authors derived risk tertiles and found that survivors in the highest risk tertile had approximately double the risk of late‑onset depression compared with those in the lowest tertile, indicating potential utility of multivariable risk prediction to target surveillance and interventions in survivorship clinics and primary care.
Expert commentary and interpretation
This study provides robust, population‑level evidence that a meaningful minority of older long‑term cancer survivors develop depression years after diagnosis — an interval when many survivors transition out of oncology follow‑up and into primary care. Key strengths include the large, population‑based sample, use of longitudinal claims to exclude prevalent depression, and appropriate competing‑risk methods (Fine‑Gray modeling) to account for mortality as a censoring/competing event. Fine and Gray’s subdistribution hazard approach is now standard for analyses where death may preclude occurrence of the outcome of interest and gives interpretable cumulative incidence comparisons across exposure groups.
Biological and psychosocial plausibility
Multiple pathways plausibly link cancer survivorship and late‑onset depression: persistent physical symptoms (e.g., pain, fatigue), treatment sequelae (e.g., hormonal therapy effects, sexual dysfunction), neuroinflammation, cumulative stress and existential distress, loss of social and occupational roles, financial toxicity, and limited access to behavioral health care. The observed associations with dual eligibility and comorbidity underscore the intersection of social determinants and medical complexity in driving depression risk.
Limitations
- Use of claims data and a claims‑based depression algorithm: while useful for population surveillance, claims under‑capture subthreshold depression and may miss cases managed without diagnostic coding. Sensitivity and specificity depend on algorithm thresholds. The approach favors detection of clinically recognized and treated depression rather than all symptomatic cases.
- Generalizability: the cohort includes fee‑for‑service Medicare beneficiaries aged ≥66, limiting application to younger survivors and those enrolled in Medicare Advantage plans. Patterns of mental health care and sociodemographic risk differ in those populations.
- Residual confounding: unmeasured factors such as social support, bereavement, functional decline, health behaviors, chemotherapy neurotoxicity details, and cancer recurrence may influence depression risk but are imperfectly captured in registry and claims data.
- Timing and causal inference: the retrospective observational design identifies associations but cannot prove causation between exposures (e.g., radiotherapy ± ADT) and later depression.
Clinical implications and recommendations
For clinicians and survivorship program leaders, several practical actions follow from these findings:
- Extend vigilance for depressive symptoms beyond the immediate post‑treatment period: routine screening for depression should be considered throughout long‑term follow‑up, not only during active surveillance. Existing guidelines such as the NCCN Distress Management recommendations provide frameworks for screening and stepped care in oncology settings.
- Prioritize high‑risk groups: dual‑eligible survivors, those with preexisting anxiety, and survivors with a high comorbidity burden warrant proactive outreach, regular screening (PHQ‑2 followed by PHQ‑9 or equivalent), and facilitated access to behavioral health services.
- Coordinate survivorship care: use survivorship care plans and explicit handoffs to primary care to ensure mental health surveillance continues after oncology discharge. Integrating behavioral health into survivorship clinics or providing tele‑behavioral health options may overcome access barriers, particularly for socioeconomically disadvantaged survivors.
- Address social determinants: dual eligibility signals socioeconomic vulnerability. Screening for social needs (transportation, financial strain, caregiving resources) and linking to social work, community resources, and patient navigation may mitigate drivers of depression.
Research gaps and future directions
Key avenues for additional research include:
- Validation and extension of risk prediction tools: translating multivariable predictors into validated, user‑friendly risk calculators for clinical use—ideally incorporating patient‑reported outcomes and social determinants—would guide targeted surveillance.
- Intervention trials in high‑risk survivors: randomized trials testing stepped care, collaborative care models, or targeted psychosocial interventions for dual‑eligible or high‑comorbidity survivors are needed to quantify benefits on symptom burden and downstream outcomes.
- Broader population studies: replication in younger cohorts and Medicare Advantage populations, and work that includes more granular data on recurrence, social support, and functional status, will improve generalizability and causal inference.
- Mechanistic studies: investigations into biological (e.g., neuroinflammation, hormonal changes) and psychosocial mechanisms driving late‑onset depression after specific treatments (e.g., ADT) could inform prevention strategies.
Conclusion
Taylor et al.’s SEER‑Medicare analysis highlights that late‑onset depression affects a substantial proportion of older long‑term survivors of breast, colorectal, and prostate cancer, disproportionately impacting survivors with socioeconomic vulnerability, higher comorbidity burden, and preexisting anxiety. These findings argue for sustained mental health surveillance across survivorship, targeted support for high‑risk groups, and integrated care models that bridge oncology and primary care to reduce disparities in detection and treatment.
Funding and clinicaltrials.gov
Funding and detailed trial or registry support information are reported in the original article: Taylor M, Westvold SJ, Long JB, et al. Risk of Late‑Onset Depression in Long‑Term Survivors of Breast, Prostate, and Colorectal Cancer. JAMA Netw Open. 2025;8(11):e2544812. Readers should consult the published manuscript for specific funding disclosures and acknowledgments.
References
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