Abstract
High-risk prostate cancer is traditionally treated with a combination of radiotherapy (RT) and androgen deprivation therapy (ADT). However, recent advancements in systemic treatment and radiotherapy have widened the spectrum of treatment for this patient population. Use of image guidance and intensity modulation, as well as the incorporation of brachytherapy, has led to safe radiotherapy dose escalation with reduced risk of recurrence. Clinical trials have helped define the role of pelvic nodal radiotherapy, the role of stereotactic ablative radiotherapy, and the optimal duration and sequencing of ADT in combination with radiotherapy. Emerging evidence has redefined the role of surgery in this cohort. Contemporary clinical trials have identified new systemic therapy options in high-risk prostate cancer. Finally, new imaging modalities including multi-parametric MRI and molecular imaging and genomic classifiers have ushered a new era in patient selection, risk stratification, and treatment tailoring.