Systemic therapies for non-metastatic prostate cancer: review of the literature

The standard treatment options based on the risk category for non-metastatic prostate cancer include surgery, radiotherapy, and watchful waiting (and more recently, active surveillance). The treatment outcome is satisfactory in low-risk disease, while a significant percentage of the intermediate-and high-risk tumor patients develop metastatic disease and die of the prostate cancer. Therefore, although developed for metastatic disease, systemic therapies have been introduced, in association with local therapies, in the management of non-metastatic prostate cancer. A recent meta-analysis showed that neither neoadjuvant nor adjuvant androgen deprivation combined with prostatectomy improves biochemical control, or disease-free and overall survival. Contrarily, addition of androgen deprivation to radiotherapy improves biochemical control, local and distant control, and overall survival in high-risk and selected intermediate-risk patients. Recent randomized trials showing the activity of new chemotherapeutic agents (such as docetaxel) prompted the launching of phase II and III trials addressing the role of chemotherapy in combination with local and/or hormonal therapy in high-risk non-metastatic disease. The ongoing trials will hopefully further define the role of systemic therapies in prostate cancer and explore the less toxic agents/combinations in order to improve the treatment outcome without excessive side effects