Abstract: PD72-01
Sources of Funding: Takeda

Introduction

Data comparing androgen-deprivation therapy (ADT) combined with external beam radiation therapy (EBRT) versus EBRT-alone have clearly demonstrated a survival benefit for the combined strategy in localized prostate cancer. Data comparing ADT alone with ADT+EBRT combinations are scarcer and this study aims to investigate oncological outcomes with long-term follow-up.

Methods

This multicenter phase III trial included 273 patients with biopsy-proven locally advanced prostate cancer (T3-4) randomly assigned to ADT alone or ADT+EBRT. Luteinizing hormone-releasing hormone (LHRH) agonist (leuprorelin 11.25 mg, subcutaneous) was started within seven days of randomization and continued every three months for three years in both arms. Oral flutamide (750 mg/day) was administered during the first month. The whole pelvis was treated at a dose of 46+/-2 Gy and the prostate with a boost from 20 Gy to 28 Gy. The primary objective was 5-year progresion-free Survival (PFS) according to clinical or biochemical criteria, using the ASTRO-Phoenix definition. Secondary endpoints consisted of overall survival (OS), disease-specific survival (DSS), locoregional progression free survival (LPFS), metastasis-free survival (MFS), time to metastatic progression, biochemical progression free survival (BPFS) and tolerance.

Results

With a median follow-up of 7.3 years, 263 patients were included in the Intent-to-treat analyses. The 8-year PFS rate was significantly higher in the ADT+EBRT arm than in the ADT-alone arm (47.9% versus 7.0%; hazard ratio: 0.27, log-rank p<0.0001). The risk of death from prostate cancer was significantly reduced in the ADT+EBRT arm as compared to the ADT-alone arm (sub-hazard ratio (SHR): 0.48; Gray’s test p=0.02). The 8-year OS rate was respectively 56.8% in the ADT-alone arm and 65.1% in the ADT+EBRT arm (log-rank p=0.43). LPFS was significantly in favor of ADT+EBRT arm (SHR = 0.61; Gray’s test p=0.01). MFS was comparable between both arms (Gray’s test p=0.88). Analysis of toxicities revealed acute lower tolerance (mainly gastro-intestinal and genito-urinary) in the ADT+EBRT arm with a gradual decrease in intensity during follow up from 6 months after the end of EBRT.

Conclusions

These long-term results confirm the oncological benefit of combining EBRT with ADT in the treatment of locally advanced prostate cancer.

Funding

Takeda