Imaging and treatment recommendations in patients with castrate-resistant prostate cancer.

Abstract

Castrate-resistant prostate cancer (CRPC) is a form of advanced prostate cancer that is resistant to medical or surgical treatments to lower testosterone, and has spread to other parts of the body. Over 80% of men with CRPC (M0) will progress to metastatic castrate-resistant prostate cancer (mCRPC), with progression being quite rapid in over half of patients. A great deal of controversy exists on how these patients should be studied and treated. Prognosis is associated with several key factors, including the presence of bone pain, extent of disease on bone scan, and performance status. Bone metastases will occur in 90% of men with CRPC and can produce significant morbidity including pain, pathological fractures, spinal cord compression, and bone marrow failure. CRPC represents a spectrum of disease ranging from patients without metastasis or symptoms with rising prostate-specific antigen (PSA) levels despite androgen deprivation therapy to patients with metastasis and significant debilitation due to cancer symptoms. Recent therapeutic advances have shown a significant survival advantage with monotherapy in trials with mCRPC patients. Optimal use of chemotherapy, second-generation androgen pathway inhibitors, immunotherapy, and targeted alpha therapy to achieve maximum clinical benefit has not been established. There are very few head-to-head studies that exist in the literature, and, as such, treatment decisions are based on limited nonrandomized comparisons. In addition, consideration of safety and tolerability are extremely important in choosing final treatments for this group of patients. The Prostate Cancer Radiographic Assessment for Detection of Advanced Recurrence Working Group (Radar 1 Group) is composed of medical oncologists, radiation oncologists, urologists, and nuclear medicine specialists, and tasked to provide recommendations for early identification of metastases in patients with prostate cancer. One of the key objectives of the working group was to provide a consensus regarding sequencing, combination, and “therapeutic layering” (the clinical point where one or more agents is added onto an existing therapy). Currently, mCRPC is incurable. The goal of treatment is to extend life and provide the best quality of life for patients for as long as possible. Six agents have achieved US Food and Drug Administration approval. These agents can prolong survival. Current treatment guidelines include sipuleucel-T, docetaxel, abiraterone acetate, enzalutamide, carbazitaxel, and radium RA 223 dichloride. In addition to these agents, supportive treatments such as the bone-health modifiers denosumab and zolendronic