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



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.



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.



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.
Department of Urology, Rabin Medical Center, Petach Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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R
Mano
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Eastham
Department of Urology, Rabin Medical Center, Petach Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Yossepowitch
D000726:Androgen Antagonists / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy / Q000379:methods; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D018714:Radiotherapy, Adjuvant / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
D000726:Androgen Antagonists