Neoadjuvant intraprostatic immunotherapy for high-risk localized prostate cancer.

High-risk localized prostate cancer is associated with substantial recurrence rates despite definitive treatment, and no neoadjuvant therapies are currently established. Investigation in this field has largely focused on systemic neoadjuvant androgen deprivation therapy, which is associated with burdensome adverse effects and long-term morbidity. Intraprostatic immunotherapy is an emerging strategy designed to overcome local immune suppression and induce systemic antitumour responses through direct modulation of the tumour microenvironment. Early-phase clinical experience with viral-vector-based gene therapies has shown this approach to be safe, technically feasible and capable of eliciting local and systemic immune activation. Clinical efficacy remains unproven, with results from early-phase studies indicating variable responses in levels of prostate-specific antigen and pathological tumour regression. Nevertheless, these studies establish a proof-of-concept for localized immunomodulation before surgery. Further progress will require standardized biological and clinical end points and rational integration with contemporary treatment modalities.