Concomitant and adjuvant androgen deprivation (ADT) with external beam irradiation (RT) for locally advanced prostate cancer: 6 months versus 3 years ADT--Results of the randomized EORTC Phase III trial 22961
Scientific Session: Concomitant and adjuvant androgen deprivation (ADT) with external beam irradiation (RT) for locally advanced prostate cancer: 6 months versus 3 years ADT--Results of the randomized EORTC Phase III trial 22961
The optimal duration of hormone therapy for locally advanced prostate cancer remains controversial. Since the EORTC 22863 trial, 3 years of androgen ablation (AA) after surgery with external beam radiation (EBRT) has become the standard of care. However, AA can have serious side effects, including increased risk of heart disease, diabetes, and bone loss, so limiting the duration of therapy to what is effective while reducing risk of side effects is important. Six months of AA combined with EBRT has been shown to be sufficient to significantly improve five-year overall survival compared with EBRT alone. The present phase III, randomized study compared six months of AA and a course of EBRT with three years of AA and a course of EBRT.
Patients with T1c-T4 disease, N0 or N1 status, and a serum PSA of less than 150 ng/ml were eligible for the study. Patients were treated with concurrent EBRT and AA, followed by AA with triptoreline, goserelin, flutamide, or bicalutamide, for a total of six months. They were then randomized to no further treatment (SADT) or 2.5 additional years of AA (LADT arm).
Progression occurred in 159 patients in the SADT arm and 61 in the LADT arm. These patients were treated with secondary hormone therapy. Progression-free survival (PFS: survival without disease progression) at five years was 81.8% in the LADT arm and 69% in the SADT arm. Biochemical PFS at five years was 78.27% in the LADT arm and 58.93% in the SADT arm.
This is the first study to show that six months of AA is not equivalent to 3 years of therapy. Combining data from this study as well as previous studies of long term AA (Bolla Lancet 2002), it appears that at present the standard of care for locally advanced prostate cancer is three years of AA with EBRT, despite the health risks. Prior studies have suggested that intermittent AA may be as effective as continuous AA in the treatment of metastatic disease. Future studies to determine whether intermittent AA used in the adjuvant setting (after surgery/radiation without metastasis) is as effective as continuous AA would provide valuable information. Intermittent AA has the potential to limit some of the previously mentioned toxicities.