Current role of neoadjuvant and adjuvant systemic therapy for high-risk localized prostate cancer

Although most men are diagnosed with readily curable localized prostate cancer, those with high-risk features face a significant mortality risk. Androgen deprivation therapy (ADT) is a standard adjunct to radiotherapy for high-risk prostate cancer, but its role around prostatectomy has not been as clearly defined, and concerns over cardiovascular toxicity have led to decreasing use. The use of chemotherapy for localized disease remains experimental. We review the most recently published trials of neoadjuvant or adjuvant systemic therapy for prostate cancer.

The optimal duration of ADT with higher dose modern radiation techniques is under active investigation, but current data support the use of longer duration as standard. Prostate-specific antigen (PSA) and MRI changes may be useful in future studies optimizing duration of neoadjuvant ADT. Two years of combined ADT after prostatectomy is associated with a lower risk of disease recurrence and better prostate cancer specific mortality than predicted. Persistence of intraprostatic androgens during neoadjuvant ADT may contribute to resistance.

Androgen deprivation added to definitive radiation or surgery improves outcomes for high-risk prostate cancer, although the role of chemotherapy remains undefined. Molecular classification is needed to improve risk stratification.