Treatment Intensification Prior to Radical Prostatectomy for Clinically Localized Prostate Cancer

Current guidelines recommend either radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT) for unfavorable intermediate- or high-risk prostate cancer. There has been emerging interest in the potential benefits of neoadjuvant ADT prior to RP for this population. Past trials indicate neoadjuvant ADT may be associated with reduced surgical complexity, pathologic downstaging, decreased positive margins, and decreased rates of nodal positivity, although they have not shown benefits for cancer progression and survival. Accordingly, neoadjuvant ADT is currently not recommended for surgical patients. Conversely, ADT is a mainstay of treatment in metastatic disease, and interest remains in expanding its use towards patients with clinically localized disease. There are several ongoing trials of second-generation androgen blockers such as enzalutamide, darolutamide, radiopharmaceuticals, and poly (ADP-ribose) polymerase (PARP) inhibitors to explore long-term cancer-specific survival benefits with neoadjuvant use. In this narrative review, we provide a comprehensive overview of the recent literature and ongoing efforts to incorporate neoadjuvant therapy for clinically localized prostate cancer patients who are at high-risk of recurrence after prostatectomy.