Abstract
Radical prostatectomy (RP) remains a standard treatment option for clinically localized high-risk prostate cancer. While RP provides excellent local control, patients with high-risk disease remain at considerable risk for recurrence after surgery. Disease relapse may be the result of occult distant metastases or regional micrometastatic disease at the time of surgery. Accordingly, the role of systemic (neoadjuvant) therapy prior to RP has been investigated. Proposed neoadjuvant regimens: include monotherapy or combinations of chemotherapy, hormonal deprivation, and immunologic agents. Randomized trials using androgen deprivation have demonstrated improved pathologic outcomes, including pathologic downstaging and decreased risk of positive surgical margins, extracapsular extension, and seminal vesical invasion. However, these, albeit early, trials did not reliably demonstrate improved post-prostatectomy oncologic outcomes. More recent trials have evaluated novel combinations of chemo-hormonal therapy and immunologic based therapies. These studies are currently maturing and offer the promise, pending findings, of potentially informing future practice. In this review, we highlight the pathophysiologic basis and contemporary evidence for neoadjuvant therapy prior to RP for clinically localized high-risk prostate cancer.
Highlights
Prostate cancer remains as one of the commonest cancers in the developed world, of which a majority are clinically organ-confined at diagnosis [1]
Controversy regarding radical prostatectomy (RP) in clinically localized high-risk prostate cancer exists due to a higher risk biochemical-recurrence (BCR) compared to RP performed in men with lower-risk prostate cancer
Neoadjuvant chemohormonal therapy was associated with a reduced risk of biochemical recurrence, compared to RP alone (p=0.021)
Summary
Prostate cancer remains as one of the commonest cancers in the developed world, of which a majority are clinically organ-confined at diagnosis [1]. Multiple trials have evaluated conventional ADT agents (LHRH analogues with or without first generation antiandrogens) in the setting of neoadjuvant therapy before radical prostatectomy for patients with clinically localized high risk-prostate cancer. McKay et al recently assessed 6-months of neoadjuvant androgen blockade by means of either LHRH agonist with enzalutamide plus/minus the additional of abiraterone This trial enrolled 75 patients and reported a trend of complete pathologic response or MRD favoring the addition of abiraterone, without reaching statistical significance (30% v 16%, p=0.263). Data from these trials suggest intense castration with two novel anti-
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