Fifteen-year survival analysis from the ASCENDE-RT randomized trial of external beam boost versus brachytherapy boost in localized prostate cancer.

Abstract

306 Background: Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) trial randomized patients to prostate brachytherapy (PB) or the External beam RT (EBRT) boost (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the EBRT arm received an additional 32 Gy in 16 fractions, and those in the PB arm received a 115 Gy 125I implant. The trial previously demonstrated a large difference in biochemical relapse favoring brachytherapy (PB) boost. At present, the median follow-up from start of treatment of all patients is 15 (IQR 10.7, 17.8) years. Herein we report the 15-year actuarial survival events. Methods: Two hundred patients with a median age of 68 (IQR 62,73) were randomized to EBRT and 198 to PB. Active study follow-up stopped at 10 years. Cause of death was determined on chart review and study report forms during active study follow-up, and was augmented with death registry data, and medical records audits thereafter. Fifteen-year overall survival and cumulative risk of death from prostate cancer were estimated using Cox and Fine and Gray analysis respectively with multivariable analysis (MVA) significant variables on univariate including - randomization, clinical T stage, log of initial PSA, Gleason grade group (1-3 vs 4-5), percent positive cores, and age at treatment. A sensitivity analysis included unknown cause of death as prostate death. Results: 213 patients (54%) have died: 64 (16%) of prostate cancer, 48 (12%) of other cancer, 35 (9%) of cardiovascular disease, 49 (12%) of other known causes, and 17 (4%) of unknown cause of death. The age of patients alive at last censoring was 82 (IQR 77,88). Overall survival at 15 years was 55.0% (95% CI 48.4 – 62.4) and 60.9% (95% CI 54.4 – 68.1) for EBRT and PB arms respectively, (HR 1.02, 95%CI 0.78 – 1.33, p = 0.908 on MVA). The cumulative incidence of prostate death at 15 years was 8.6% (95%CI 5.2 – 13.0) for PB and 16.4% (95%CI 11.6 – 22.0) for EBRT (p=0.007). In a sensitivity analysis where cases of unknown cause of death were counted as prostate deaths, the cumulative incidence of prostate death at 15 years was 14.3% (95%CI 9.8 – 19.5) for PB and 19.4% (95%CI 14.2 – 25.3) for EBRT (p=0.067). Conclusions: At 15 years, there is no definite evidence of an overall survival benefit with PB boost in ASCENDE-RT and the trend to a prostate cancer specific survival advantage with PB is limited by ascertainment of cause of death. Thus, although prostate cancer was the single most common cause of mortality in ASCENDE-RT, our results suggest that even large improvements in b-NED, such as those demonstrated with PB in ASCENDE-RT, are unlikely to improve 15-year overall survival by more than 10% for a population whose median age, performance status, and prognostic variables are similar to ASCENDE-RT participants. Clinical trial information: NCT00175396 .