OBJECTIVES: Prostate cancer is the second leading cause of cancer mortality in American men. Androgen deprivation therapy (ADT) is the standard initial treatment for advanced disease, but most patients eventually develop HRPC.  There are no universally accepted, standardized and objective criteria for assessing response to treatment for HRPC, so patient-reported outcomes (PRO) are a critical in guiding and monitoring palliative interventions.  We characterized the prevalence and natural history of symptoms in patients with hormone refractory, incurable prostate cancer. METHODS: Patients with HRPC receiving care at Dana-Farber Cancer Institute, completed a questionnaire at each clinic visit over 10 months, comprising the Quality of Life Index (QLI), Rotterdam Symptom Checklist (RSCL), Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), American Urological Association symptom index (AUA), and the ECOG performance status scale. RESULTS: A total of 87 of 102 eligible patients enrolled. Among participants, the survey response rate was 98%.   A total of 87% had documented metastases; the remainder had rising prostate specific antigen levels despite ADT.  The following frequencies of symptoms were reported at baseline and during follow-up (worst scores ever), respectively: urinary symptoms, moderate/severe: 62 v. 75 %; any pain, 67 v. 70%; severe intensity in worst pain score, 19 v. 25%; HADS possible/probable diagnosis: anxiety, 21 v. 39%, depression, 20 v. 35%; ECOG PS 2+, 15 v. 37%;  RSCL symptoms: tiredeness, 30 v. 60%; lack of energy, 28 v. 58%; muscle soreness, 26 v. 45%.  The mean overall health rating (0=worst, 100=best) was, 74 at baseline v. 56 during follow up. A shift toward lower levels of HRQL was also observed across all domains of the QLI.  CONCLUSIONS: Patients with HRPC endure a substantial and worsening symptom burden over time.  Given the high prevalence of symptoms and difficulty of assessing treatment response by objective measures in this disease, PRO should be routinely incorporated into clinical care and trials.