Results of a multicenter, randomized, phase 3 trial of trimodality therapy with I-125 brachytherapy, external beam radiation therapy, and long- versus short-term androgen deprivation therapy for localized high-risk prostate cancer (TRIP/TRIGU0907).

305 Background: The TRIP trial was a multicenter, phase 3 randomized investigation designed to determine whether 30 months of androgen deprivation therapy (ADT) was superior to 6 months of ADT when combined with brachytherapy and external beam radiotherapy (EBRT) for localized high-risk prostate cancer. Methods: The trial was done in 37 hospitals in Japan. Men between 40 to 79 years old with stage T2c-3a, or a prostate-specific antigen (PSA) >20 ng/ml or a Gleason score >7 received 6 months of ADT combined with I-125 brachytherapy at a prescription dose of 110 Gy, followed by EBRT of 45 Gy. Patients were randomly assigned either no further treatment (short arm) or 24 months of adjuvant ADT (long arm) after stratification. The primary endpoint was biochemical progression-free survival using the Phoenix definition of failure. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific survival, overall survival, and grade 3 or higher of adverse events. An intention-to-treat analysis was conducted with survival estimates determined using competing risk analyses. Results: Of 332 patients, 165 were randomized to the short and 167 to the long arm. The median follow-up periods were 9.43 and 9.24 years, respectively. 24 patients have died in each arm. The cumulative incidence for biochemical progression in the short vs. long arm were 10.4% (95% confidence interval [CI] 6.62-16.42) vs 9.5% (5.85-15.46) at 9 years, respectively (p=0.647). The cumulative incidences for clinical progression, distant metastases, salvage treatment, and disease-specific mortality events were not significantly different between the two arms. The overall survival rates of the short arm vs long arm were 87.2% (82.13-92.63%) and 85.9% (80.41-91.77%) at 9 years, respectively (p=0.914). Endocrine-related grade 3 morbidity for short arm vs long arm was 0.6% vs 1.8% (p=0.623), and radiation-related grade 3 morbidity was 1.2% vs 0.6% (p=0.622). Conclusions: In localized high-risk prostate cancer, TRIP did not demonstrate the superiority of 30 months vs. 6 months of ADT when combined with brachytherapy and EBRT. These data suggest that ultra-high radiation doses can be combined with a shorter course of ADT without compromising survival. Clinical trial information: UMIN000003992 .