Background: The objective of this study was to construct and validate a brief, clinically-relevant symptom index for advanced prostate cancer. Methods: Questions were extracted from a commonly-used multi-dimensional cancer quality of life instrument with prostate-specific items, the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Surveys of disease-related symptoms were presented to an international sample of 44 expert physicians. Each expert narrowed the list to no more than five of the most important symptoms or concerns to monitor when assessing the value of treatment for advanced prostate cancer. Symptoms/concerns endorsed at a frequency greater than chance probability (17%) were retained for the symptom index and called the FACT Advanced Prostate Symptom Index-8 (FAPSI-8): pain (three items), fatigue, weight loss, urinary difficulties (two items), and concern about the condition becoming worse. The FAPSI-8 was validated using data from a clinical trial of 288 men being treated for hormone refractory prostate cancer. Results: The FAPSI-8 showed good internal consistency (r = 0.67-0.80); association with existing FACT scales (e.g., FACT-P, Physical Well-being, Functional Well-being; r = 0.44 - 0.85, p < .0001), responsiveness to clinical change (Guyatt's Responsiveness statistic = 1.29), and ability to differentiate patients by performance status (p < .0001). A six-item alternate version of the FAPSI was also evaluated with comparable results. Conclusions: This project produced a reliable and valid list of the eight most important clinician-rated targets of drug therapy for advanced prostate cancer. These questions perform comparably to the longer derivative questionnaire. Examination of patient agreement with this priority list and the extent to which changes in these 8 targets are related to meaningful clinical benefit to the patient are important next steps for future research.