10-Year Results of a Phase III Randomized Trial of High-Dose Radiotherapy and Risk-Adapted Androgen Deprivation in Localized Prostate Cancer

Abstract

<h3>Purpose/Objective(s)</h3> The optimal duration of androgen deprivation (AD) combined with high-dose radiotherapy (HDRT) in prostate cancer remains a matter of controversy. We did a phase 3 trial designed to determine whether long-term AD (LTAD) is superior to short-term AD (STAD) when combined with HDRT. In this report, we present the 10-year survival results. The hypothesis is that long-term AD (LTAD) compared to short-term AD (STAD) improves overall survival among high-risk patients receiving HDRT. <h3>Materials/Methods</h3> This open-label, phase 3 randomized controlled trial, recruited patients from ten university hospitals throughout Spain. Eligibility included patients with cT1c-T3aN0M0 adenocarcinoma of prostate with intermediate and high-risk factors according to NCCN criteria and PSA less than 100 ng/ml. All patients received 4 months of neoadjuvant and concomitant AD (STAD) + HDRT (median radiation dose 78 Gy) before randomization to adjuvant goserelin for two years (LTAD). Stratification was performed according to risk group (intermediate risk [IR] versus high risk [HR]). Study endpoints included overall survival (OS), metastasis free survival (MFS), disease free survival (DFS) and biochemical-disease free survival (bDFS). Survival analyses were done with Kaplan-Meier (KM) curves. Fine & Gray (F&G) regression was used for the adjusted analyses. <h3>Results</h3> From 2005 to 2010, 355 patients were randomly assigned to the treatment groups and included in the analysis (178 to STAD and 177 to LTAD). The median follow-up was 119 months (IQR 101-124). The 10-year bDFS for LTAD and STAD was 70.2% and 62.3% respectively (hazard ratio [HR] 1.19, 95% CI, 0.71 to 2.01). The 10-year OS was 78.4% for LTAD and 73.3% for STAD (HR 1.20, 95% CI, 0.79 to 1.82), and the corresponding figure for MFS was 76.0% and 70.9% for LTAD and STAD respectively (HR 1.12, 95% CI, 0.46 to 2.73). For high-risk patients treated with LTAD, the 10-year bDFS was 67.2% compared to 53.7% for STAD (log rank <i>P</i> = 0.03; F&G <i>P</i> = 0.147, HR 1.12 95% CI 0.61 to 2.04). The 10-year OS was 78.5% compared to 67.0% for STAD (log rank, <i>P</i> = 0.056; F&G <i>P</i> = 0.786, HR, 1.18, 95% CI, 0.36 to 3.84) and the 10-year MFS was 76.6% versus 65.0% for LTAD and STAD respectively (log rank <i>P</i> = 0.069; F&G <i>P</i> = 0.057, HR, 1.12, 95% CI, 0.46 to 2.73). Only 11 patients died from PCa, all of them in the high-risk subgroup. <h3>Conclusion</h3> Long term results failed to show a significant benefit with LTAD compared to STAD in patients treated with HDRT. The subgroup of patients with high-risk PCa treated with LTAD had a non-significant improvement in bDFS, MFS and OS compared with STAD<i>.</i> The relatively small simple size, a low number of events and an effective salvage treatment could be responsible for the lack of a statistical significance. The trial is registered at ClinicalTrials.gov, number NCT 02175212.