Risk of Late-Onset Depression in Long-Term Survivors of Breast, Prostate, and Colorectal Cancer

The prevalence of depression is higher in cancer survivors than in the general population. As the long-term cancer survivor population increases, it is increasingly important to understand risk factors for late-onset depression.

To identify risk factors associated with late-onset depression in long-term (5-year) survivors of breast, prostate, or colorectal cancer.

This retrospective cohort study used 2022 linkage of Surveillance, Epidemiology, and End Results (SEER) and Medicare data to identify 5-year survivors of breast, prostate, or colorectal cancer 66 years or older who were enrolled in fee-for-service Medicare and had no previous depression diagnosis. Long-term survivors were diagnosed with cancer between January 1, 2007, and December 31, 2012, and followed up between January 1, 2008, and December 31, 2020. Data analysis was performed from August 2024 to July 2025.

Sociodemographic and cancer-specific characteristics, treatment within 1 year after diagnosis, comorbidities within 1 year before cancer diagnosis, and previous diagnosis of anxiety.

The primary outcome was late-onset depression 5 to 10 years after cancer diagnosis, identified using a validated claims-based algorithm. Analyses were conducted separately for each survivor cohort. Fine-Gray subdistribution hazard regression, accounting for the competing risk of mortality, was used to identify factors associated with late-onset depression.

A total of 53 769 survivors were identified, including 13 265 breast, 26 979 prostate, and 13 525 colorectal cancer survivors (mean [SD] age, 74.1 [5.8] years; 31 279 [61.9%] male; 2375 [4.4%] Asian or Pacific Islander, 2691 [5.0%] Hispanic, 3906 [7.3%] non-Hispanic Black, 43 986 [81.8%] non-Hispanic White, and 811 [1.5%] other or unknown) were identified. The 5-year risk of late-onset depression was highest in breast cancer survivors (13.3% [1768 of 13 265]), compared with prostate (8.7% [2360 of 26 979]) and colorectal (11.8% [1591 of 13 525]) cancer survivors. Older age was associated with greater hazard of depression among some categories (eg, prostate cancer survivors aged ≥90 years vs 71-74 years: HR, 1.57; 95% CI, 1.10-2.24) but not among others (eg, colorectal cancer survivors aged ≥90 years vs 71-74 years: HR, 1.02; 95% CI, 0.84-1.24). Variables that were consistently associated with greater hazard of depression included Medicare-Medicaid dual eligibility (eg, dual eligible breast cancer survivors vs non-dual eligible: HR, 1.38; 95% CI, 1.22-1.57), anxiety (eg, prostate cancer survivors: HR, 2.82; 95% CI, 2.47-3.22), and comorbidity burden (eg, breast cancer survivors: HR, 1.33; 95% CI, 1.12-1.57). In prostate cancer survivors, receipt of radiotherapy with or without androgen deprivation therapy was also associated with higher risk (HR, 1.22; 95% CI, 1.10-1.36). The risk of depression among survivors in the high-risk tertile was twice as high compared with the low-risk tertile.

In this cohort study of long-term cancer survivors, Medicare and Medicaid dual eligibility, higher comorbidity burden, and preexisting anxiety were independently associated with greater risk of late-onset depression. These findings suggest that these risk factors may be used to proactively inform survivorship care during the transition from cancer surveillance to preventive care, which could reduce the risk of inconsistent follow-up care for survivors that may drive socioeconomic and racial and ethnic disparities in depression screening and treatment.