Management of High-Risk Localised Prostate Cancer

Abstract

Abstract Context High-risk localised prostate cancer (PCa) is defined as significant likelihood of death from PCa or development of distant metastases. It is important to identify patients at high risk of progression who may benefit from neoadjuvant or adjuvant therapies. Objective To review definitions for high-risk localised PCa and review outcomes of different treatment modalities. Evidence acquisition Randomised and nonrandomised clinical trials addressing the characterisation of patients with high-risk PCa and treatment options for this patient population were reviewed, mainly focusing on comparison of monotherapy with multimodality approaches. Evidence synthesis Radical prostatectomy (RP) represents a treatment option for selected high-risk patients and can result in long-term progression-free survival (PFS) in a subset without hormone therapy (HT). HT prior to RP is not considered as a standard treatment in high-risk, clinically localised PC, because survival advantage has never been conclusively demonstrated. Adjuvant early androgen-deprivation therapy (ADT) is not recommended for patients with high-risk disease except for pathologically confirmed nodal disease. Adjuvant radiotherapy (RT) after RP in patients with adverse risk factors decreases biochemical recurrence risk with improved local control but without a clear advantage in overall survival (OS). RT with long-term adjuvant HT improves OS. However, the exact period of HT is still controversial, and one must consider the cardiovascular comorbidity status of the patients before initiating ADT. Neoadjuvant chemotherapy can be administered safely in patients with high-risk disease prior to definitive therapy. Although complete responders are very rare, prostate-specific antigen (PSA) responses were present in a substantial number of patients. Early results of adjuvant chemotherapy trials are promising, but ongoing phase 3 trials should be completed to establish any survival advantage. Conclusions Integrating local and systemic therapies may be beneficial in the management of high-risk localised or locally advanced PCa.