Long-term androgen deprivation, with or without radiotherapy, in locally advanced prostate cancer: updated results from a phase III randomised trial

Objectives: To report the long-term oncological outcomes of a randomised trial comparing androgen-deprivation therapy (ADT) combined with external beam radiation therapy (EBRT) and ADT alone in patients with locally advanced prostate cancer.

Patients and methods: In this multicentre phase III trial, patients were randomly assigned to ADT alone or ADT+EBRT. Leuprorelin 11.25 mg was administered for 3 years. The whole pelvis was treated at a dose of 46 Gy and the prostate with a boost from 20 to 28 Gy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), disease-specific survival (DSS), locoregional PFS (LRPFS), metastasis-free survival (MFS), biochemical PFS (BPFS), and tolerance.

Results: With a median follow-up of 7.3 years, 263 patients were included. The 8-year PFS rate was significantly higher in the ADT+EBRT arm than in the ADT arm (48% vs 7%; hazard ratio [HR] 0.27, 95% confidence interval [CI] 0.17-0.39; P < 0.001); in patients with a baseline PSA level ≥50 ng/mL (HR 0.10, 95% CI 0.05-0.20; P < 0.001) and in patients with a baseline PSA level <50 ng/mL (HR 0.28, 95% CI 0.19-0.40; P < 0.001). The risk of death from prostate cancer was significantly reduced in the ADT+EBRT arm (sub-HR [SHR] 0.48, 95% CI 0.25-0.91; P = 0.02). The 8-year OS rate was 57% in the ADT arm and 65% in the ADT+EBRT arm (no significant difference). LRPFS was significantly in favour of the ADT+EBRT arm (SHR 0.61, 95% CI 0.42-0.89; P = 0.01). MFS was comparable between both arms (P = 0.88). Analysis of toxicities revealed acute lower tolerance in the ADT+EBRT arm, with a gradual decrease in intensity 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.