Dose escalated external beam radiotherapy versus neoadjuvant androgen deprivation therapy and conventional dose external beam radiotherapy for clinically localized prostate cancer: do we need both?

Purpose: several randomized trials have demonstrated that men with localized prostate cancer benefit from the use of short-term neoadjuvant androgen deprivation therapy (NADT) in combination with external beam radiotherapy (EBRT), while other trials have shown improved outcomes with higher doses of radiation. This review compares both approaches and the rationale for using both. Materials and methods: to date 4 randomized trials, including 10 arms and ∝1600 men have reported comparing patients treated with EBRT alone to EBRT combined with short-term NADT. To date, four Phase III dose escalation trials have been completed including 8 arms and a total of ∝2210 patients with doses up to 74 to 79 Gy compared to doses of 64 to 70 Gy on the control arms. Results: all studies (n = 4) using NADT demonstrated an improvement in biochemical failure compared to patients treated with EBRT alone, three studies showed an improvement in cause specific survival and one showed an overall survival advantage, one showed a reduction in distant metastasis or the need for salvage ADT. All phase III dose escalation studies to date only show an improvement in biochemical control. Conclusions: the quality of the evidence supporting the use of NADT in combination with EBRT for clinically important endpoints is stronger than the data supporting dose escalation. Cure rates appear to be unacceptably low for both approaches such that higher doses of EBRT combined with NADT and whole pelvic radiotherapy may be indicated for optimal outcomes. (orig.)