This program project will use a disease-site oriented approach to address the hypothesis: hyperthermia delivered as an adjuvant to radiation therapy will improve the clinical outcome of patients with prostate cancer resulting in organ preservation, a reduced probability of recurrence, improved quality of life and superior survival. Three Projects and three Cores will bring together technical, biological and clinical expertise to focus on prostate cancer hyperthermia. The proper understanding of the clinical results, whether or not they are positive, requires relating athe technical parameters of the hyperthermia treatment with basic hyperthermia biology using the appropriate tumor systems. (Bernstein 0018). Clinical Project will deliver hyperthermia to patients with prostate cancer using the ultrasound probe developed by our collaborator, De. Hynynen. Temperature and perfusion will be measured using the profilometer probes developed in this grant. A second clinical goal is to complete testing of the Focused Segmented Ultrasound machine developed in the previous grant period. A third clinical research effort will be the continued clinical evaluation of hyperthermia modifiers (initially the hypoxia modifiers) designed to enhance the efficacy of temperatures obtainable ina the clinic. (Calderwood 0019). Biology Project is focused on prostate cancers using cells, tumor models and clinical biopsies to further the understanding of clinical results. In addition to the hyperthermia modifiers already developed for Project 1 the new classes of agents to be studied are the non-steroidal antiinflammatory agents and kinase inhibitors. (Newman 0017). Technology Project will develop the models and techniques required to allow hyperthermia to be used conveniently and routinely in the clinic, focusing on the use of perfusion data to adjust power deposition so that tahe targeted temperature can be maintained. (Svensson 9001). Technical, supports the clinical trials and the modeling efforts; (Teicher 9002). Animals, includes both small animals for the biologic experiments and large animals for testing the models/ and Administration, provides statistical support and provides external advice. In summary, this is a disease-site oriented program which has the long-term aim of answering the question of whether or not hyperthermia is an effective adjunctive therapy to radiation therapy for patients with cancer of the prostate.