Conventional external beam radiotherapy is suboptimal treatment for patients with locally advanced tumors of the prostate. Existing data indicate that the majority of patients with Stage C tumors will experience poor outcomes of treatment, when measured by the endpoints of positive post-treatment prostatic biopsies or by elevated post-treatment levels of Prostate Specific Antigen (PSA). Advances in diagnostic imaging of the pelvis, coupled with increasing sophistication and speed of radiation treatment planning hardware and software, now permit planning and execution of sophisticated radiation treatment plans of unprecedented complexity and, potentially, unprecedented accuracy. These developments are now at the stage where the question of radiation dose escalation to the prostate can be tested as an approach to overcoming the limitations of conventional treatment. The Department of Radiation Oncology at the University of Washington has a longstanding research commitment to many aspects of both conformal therapy and prostatic cancer treatment, and is a logical participant in the proposed collaborative group. The development of radiation treatment planning software is a major research focus of the investigators, through their participation in the NCI Radiotherapy Treatment Planning Tools contract. The investigators' commitment to clinical prostate cancer trials is substantiated by the department's established leadership in clinical trial development, patient accrual, and timely completion of prior NCI-sponsored prospective collaborative trials for prostatic cancer. The substantial equipment resources necessary for such an undertaking, involving multi-leaf collimator equipped treatment machines, 3D treatment planning and evaluation software, computational hardware, real-time portal imaging, and the system network that coordinates the individual components, are in place or are in the final stages of installation. Most importantly, the human resources and expertise necessary to integrate the different facets of conformal therapy are in place, and are already active in addressing many of the concerns central to this undertaking. In this proposal, we elaborate a plan for the design and execution of clinical trials to test conformal therapy in prostatic cancer, providing specific directions where these directions are clearly definable and discussing the range of alternative approaches for areas that remain problematic.
