The very-high-risk prostate cancer: a contemporary update

Background: Treatment of high-risk prostate cancer has evolved considerably over the past two decades, yet patients with very-high-risk features may still experience poor outcome despite aggressive therapy. We review the contemporary literature focusing on current definitions, role of modern imaging and treatment alternatives in very-high-risk prostate cancer. Methods: We searched the MEDLINE database for all clinical trials or practice guidelines published in English between 2000 and 2016, with the following search terms: ‘prostatic neoplasms’ (MeSH Terms) AND (‘high risk’ (keyword) OR ‘locally advanced’ (keyword) OR ‘node positive’ (keyword)). Abstracts pertaining to very-high-risk prostate cancer were evaluated and 40 pertinent studies served as the basis for this review. Results: The term ‘very’-high-risk prostate cancer remains ill defined. The European Association of Urology and National Comprehensive Cancer Network guidelines provide the only available definitions, categorizing those with clinical stage T3–4 or minimal nodal involvement as very high risk irrespective of PSA level or biopsy Gleason score. Modern imaging with multiparametric magnetic resonance imaging and positron emission tomography-prostate-specific membrane antigen scans has a role in pre-treatment assessment. Local definitive therapy by external beam radiation combined with androgen deprivation is supported by several randomized clinical trials, whereas the role of surgery in the very-high-risk setting combined with adjuvant radiation/androgen deprivation therapy is emerging. Growing evidence suggest neoadjuvant taxane-based chemotherapy in the context of a multimodal approach may be beneficial. Conclusions: Men with very-high-risk tumors may benefit from local definitive treatment in the setting of a multimodal regimen, offering local control and possibly cure in well selected patients. Further studies are necessary to better characterize the ‘very’-high-risk category and determine the optimal therapy for the individual patient.