Addition of Radiotherapy to Long-Term Androgen Deprivation in Locally Advanced Prostate Cancer: An Open Randomised Phase 3 Trial

BackgroundRadiotherapy combined with androgen-deprivation therapy (ADT) is superior to radiotherapy alone in localised prostate cancer; however, data comparing ADT alone are somewhat limited.ObjectiveTo compare 3-yr ADT plus radiotherapy with ADT alone in locally advanced prostate cancer patients.Design, setting, and participantsA multicentre randomised open controlled phase 3 trial in 264 histologically confirmed T3–4 or pT3N0M0 prostate cancer patients randomised from March 2000 to December 2003.InterventionADT (11.25 mg subcutaneous depot injection of leuprorelin every 3 mo for 3 yr) plus external-beam radiotherapy or ADT alone. Flutamide (750 g/d) was administered for 1 mo.Outcome measurements and statistical analysisThe primary objective was 5 yr progression-free survival (PFS) according to clinical or biologic criteria, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and the newer (Phoenix) definition (nadir plus 2 ng/ml), by intention to treat. Secondary objectives included time to locoregional recurrence and distant metastases, and overall and disease-specific survival. Our Analyses: intent-to-treat analysis, multivariate analyses using a Cox model with a 5% threshold from univariate analysis, and Kaplan-Meier estimates.Results and limitationsADT alone was administered to 130 patients and combined therapy to 133. With a median follow-up of 67 mo, 5-yr PFS was 60.9% for combined therapy versus 8.5% with ADT alone (ASTRO; p < 0.0001), and 64.7% versus 15.4%, respectively, for Phoenix (p < 0.0011). Locoregional progression was reported in 9.8% of combined-therapy patients versus 29.2% with ADT alone (p < 0.0001) and metastatic progression in 3.0% versus 10.8%, respectively (p < 0.018). Overall survival was 71.4% with combined therapy versus 71.5% with ADT alone; disease-specific survival was 93.2% versus 86.2%. Limitations included the relatively small population and a relatively short follow-up period.ConclusionsCombined therapy strongly favoured improved PFS, locoregional control, and metastasis-free survival. Longer follow-up is needed to assess the potential survival impact.