Purpose: Cancer-related fatigue is one of the most debilitating side effects of cancer and cancer therapy. We aimed to investigate co-occurring symptoms associated with persistent fatigue in men receiving external beam radiation therapy (EBRT) for nonmetastatic prostate cancer. Methods: A sample of 47 men with prostate cancer scheduled to receive radiotherapy (RT) were followed at baseline and 1 year after RT. Clinical and demographic data were obtained from chart review. Symptom measurements included urinary dysfunction (American Urological Association symptoms score), fatigue (Functional Assessment of Cancer Therapy – Fatigue questionnaire), sleep disturbance (Patient-Reported Outcomes Measurement Information System – Sleep Disturbance form), pain (physical well-being domain pain item of the Functional Assessment of Cancer Therapy – General), and depressive symptoms (Hamilton Depression Rating Scale). Paired t tests, correlations, general linear models, and logistic regressions were used to determine associations between fatigue and other symptom scores. Results: At 1 year after RT, 34% of subjects continued to experience fatigue. Urinary dysfunction was the best clinical predictor of persistent fatigue. Pain and depressive symptoms further improved the predictive power of the model. A multivariate linear regression model containing all these three clinical variables (urinary dysfunction, pain, and depressive symptoms) explained 74% of total variance associated with persistent fatigue after RT. Conclusions: Persistent fatigue at 1 year after EBRT in prostate cancer survivors is likely related to a cluster of symptoms elicited by chronic inflammation. Therapies that target each of these symptoms will likely reduce fatigue in this patient population.

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