Neoadjuvant therapy in high-risk prostate cancer

High-risk prostate cancer (PCa) is associated with higher rates of biochemical recurrence, clinical recurrence, metastasis, and PCa-specific death, compared to low-and intermediate-risk disease. Herein, we review the various definitions of high-risk PCa, describe the rationale for neoadjuvant therapy prior to radical prostatectomy, and summarize the contemporary data on neoadjuvant therapies. Since the 1990s, several randomized trials of neoadjuvant androgen deprivation therapy (ADT) have consistently demonstrated improved pathological parameters, specifically tumor downstaging and reduced extraprostatic extension, seminal vesicle invasion, and positive surgical margins without improvements in cancer-specific or overall survival. These studies, however, were not exclusive to high-risk patients and were limited by suboptimal follow-up periods. Newer studies of neoadjuvant ADT in high-risk PCa show promising pathological and oncological outcomes. Recent level 1 data suggests neoadjuvant chemohormonal therapy (CHT) may improve longer-term survival in high-risk PCa. Immunologic neoadjuvant trials are in their infancy, and further study is required. Neoadjuvant therapies may be promising additions to the multimodal therapeutic landscape of high-risk and locally advanced PCa in the near future.