Low-Dose Brachytherapy Improves Disease-Free Survival in Unfavorable-Risk Prostate Cancer
Low-dose-rate brachytherapy boost achieves better rates of biochemically disease-free outcomes.
ORLANDO—Compared to dose-escalated external beam radiotherapy (DE-EBRT), iodine-125 low-dose-rate brachytherapy boost (LDR-PB) achieves better rates of biochemically disease-free outcomes, but not superior overall survival, for men with intermediate- and high-risk localized prostate cancer, according to findings from the multicenter randomized ASCENDE-RT study (Abstract 3), presented during the 2015 Genitourinary Cancers Symposium.1
“In the context of 12 months of ADT and whole pelvis radiation therapy, treatment with LDR-PB boost results in a 50% reduction in biochemical relapse compared to DE-EBRT to 78 Gy,” reported Scott Tyldesley, MD, of the BC Cancer Agency in Vancouver, British Columbia, Canada. “The absolute difference in biochemical disease-free survival at 7 years was approximately 11%.”
At 6.5 years follow-up, there was no difference in overall survival (OS), prostate cancer-specific survival, or metastasis-free survival, Dr. Tyldesley said.
LDR-PB was associated with higher rates of late grade 3 or higher genitourinary toxicity according to Dr. Tyldesley.
A total of 398 men with intermediate- (276 patients) or high-risk (122 patients) localized prostate cancer were enrolled during December 2002 through September 2011 and randomly assigned to receive either external beam radiotherapy (DE-EBERT, standard treatment arm: 200 patients) or LDR-PB (198 patients).
All participants received 12 months of androgen deprivation therapy (ADT) with luteinizing hormone releasing hormone (LHRH) agonist plus a nonsteroidal antiandrogen for at least 1 month.
After 8 months of neo-adjuvant ADT, patients in both study arms received whole-pelvis EBRT (46 Gy in 23 fractions) before being receiving either a conformal EBRT boost (32 Gy) or an iodine-125 LDR boost prescribed to a minimum peripheral dose of 115 Gy.
The primary study endpoint was relapse-free survival (RFS) determined by biochemical criteria using the nadir+2 ng/mL threshold, calculated from the date of first LHRH agonist injection.
There were 29 (7%) major protocol violations, including 14 cross-over events in which patients opted to leave their assigned study arm and receive the other treatment, and 15 men who received neither regimen.
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Intent-to-treat analysis showed that patients in the LDR-PB study arm saw a significantly longer biochemical progression-free survival (9-year PFS: 62.4 months vs. 83.3 months; P=0.001).
PFS for patients in the NCCN intermediate-risk group (122 patients) saw a greater benefit from LDR-PB (9-year PFS: 93.9 months vs. 69.8 months; P<0.001) than patients in the high-risk group (276 patients; 9-year PFS: 78 vs. 58.2 months; P=0.05). Factors predictive of RFS in a multivariate analysis included randomization (P=0.004), percent positive cores (P=0.006), initial PSA (P=0.01), and clinical T-stage (P=0.004).
By the fifth year of follow-up, LDR-PB was associated with significantly more late grade 3 genitourinary (GU) toxicities (5-year cumulative incidence of G3 toxicity: 19% LDR-PB vs. 5% for DE-EBRT; P<0.001), Dr. Tyldesley reported. This translated to an approximate 5% to 6% increase in long-term prevalence, he said. Half of late grade 3 or higher GU toxicities in the LDR-PB arm were urethral strictures.
- Morris WJ, Tyldesley S, Pai HH, et al. ASCENDE-RT*: A multicenter, randomized trial of dose-escalated external beam radiation therapy (EBRT-B) versus low-dose-rate brachytherapy (LDR-B) for men with unfavorable-risk localized prostate cancer. 2015 Genitourinary Cancers Symposium. Abstract 3.