Lack of benefit at 5 years from a short course of neoadjuvant/concurrent androgen deprivation for unfavorable prostate cancer patients treated to a high total radiation dose

Abstract

Purpose/Objective: To assess the survival impact of a course of ≤6 months of adjuvant/concurrent androgen deprivation in patients with unfavorable prostate cancer treated to a very high radiation dose with external beam (EBRT) and high dose rate (HDR) brachytherapy boosts. Materials/Methods: Between 1986 and 2002, 579 patients (pts) were treated for clinically localized prostate cancer in two prospective trials of pelvic EBRT and dose escalating HDR brachytherapy boosts. There were 201 pts treated at Kiel University and 378 pts at William Beaumont Hospital with 222 pts receiving androgen deprivation therapy (ADT) for a period of ≤6 months. For this analysis, the patient had to have a follow-up ≥18 months (3 times greater than the exposure to ADT) leaving a total sample of 475 pts. All pts had 1 of the following poor prognostic factors: Stage ≥T2b, Gleason score ≥7 and pretreatment PSA of ≥10. Pts were stratified by any one factor, 219 pts, any 2 factors 194 pts, and to improve comparability, all 3 factors in 138 pts. The ASTRO definition for biochemical failure (BF) was used. Results: The mean follow-up time for all patients was 5.1 years and for those patients with all 3 poor prognostic factors was 6.1 years (range 1.7–14.5 yrs). The 5-year actuarial analysis: a) all patients, b) ADT patients c) patients without ADT and d) patients with all 3 poor prognostic factors are listed in Table 1. We analyzed overall survival (OS), cause-specific survival (CSS), biochemical control (BC), disease free survival (DSF) and clinical local recurrence (c-LR). Of great significance is that the pts receiving a short course of ADT had a lower CSS when all 475 were analyzed p=0.015. For pts with all 3 poor risk factors giving ADT resulted not only in lower CSS p=0.009 but also in lower OS p=0.05. Multivariate analysis for biochemical control demonstrated decreasing age (p=0.039), increasing stage (p=0.008), and increasing Gleason score (<0.001) were significant for biochemical failure. While increasing PSA values, the addition of ADT, the increasing number of poor prognostic factors and the increasing length of follow-up were not predictive variables. Conclusions: EBRT with conformal HDR boosts produces excellent long term outcome in terms of OS, CSS, DFS, BC and c-LR in patients with unfavorable prostate cancer. With the high biological equivalent dose delivered with this technique, the addition of a course of <6 months of neoadjuvant/concurrent ADT to this treatment protocol does not appear to confer a therapeutic advantage. In fact, ADT, did not prevent cancer deaths, has decreased OS, resulted in lower CSS and has added side effects (sexual impotence) as well as the significant cost of hormonal treatment.