Prostate cancer is the most common cancer and the second leading cause of cancer death among men in the United States. Definitive treatment with either surgery or radiation (with or without androgen deprivation therapy, ADT) is currently guided by the National Comprehensive Cancer Network’s (NCCN) risk stratification prognostic groupings, which are based on clinical tumor stage, biopsy Gleason score (GS) and percentage of positive cores, and pretreatment serum PSA. To better prognosticate patients at diagnosis, tissue-based molecular biomarkers (i.e., Decipher and Oncotype DX Genomic Prostate Scores, and ArteraAI multimodal artificial intelligence biomarker test) and improved imaging techniques (i.e., Prostate-Specific Membrane Antigen (PSMA) radiotracer and enhanced MR capabilities) will likely be incorporated into management decisions over time. Treatment practices will continue to advance with the goals of decreasing treatment duration, reducing toxicity, and further improving cure rates. The patient’s decision to pursue a radiotherapy versus surgical approach, knowing that oncologic outcomes are equivalent, is multifactorial and based on social, psychological, financial, comorbid, toxicity, and other considerations.