Neoadjuvant hormonal therapy in the management of prostate cancer: a surgical and radiation therapy review.

Neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy is an old concept that has recently been revisited. First described in the 1940s as a method to downstage inoperable prostate cancer prior to perineal prostatectomy. NHT fell out of favor for several reasons: the side effects of estrogen therapy, the finality of orchiectomy, improved staging methods, and newer treatment strategies for prostate cancer, including external beam and interstitial radiation therapy. Contemporary interest in NHT has resurfaced primarily due to the introduction of well-tolerated reversible androgen blockade. High cause-specific survival rates following radical prostatectomy for organ confined disease are possible, yet the disturbingly high incidence of positive margins in current radical prostatectomy series led to interest in offering NHT to patients prior to radical prostatectomy to impact on the positive margin rate. Initial nonrandomized studies showed that NHT provided a substantial decrease in prostate size and PSA level in addition to reducing positive margin rate by an uncertain mechanism. Subsequently, controlled randomized studies have been performed, the majority of which have confirmed decreased margin positivity. NHT has been incorporated successfully into external beam radiotherapy for locally advanced prostate cancer as well. Significantly improved disease control is possible when hormones are combined with radiation therapy. The favorable outcome of this radiation therapy approach has led to the approval of flutamide (Eulexin) for this indication when combined with a luteinizing hormone-releasing hormone analogue or orchiectomy. Whether these initial results will ultimately affect recurrence and survival data is unknown. This article provides a comprehensive review of the world literature on NHT: from an historical prospective to the current state of the art for both radical prostatectomy and external beam radiation therapy.