ORLANDO, FL, USA (UroToday.com) - In this session, Dr. Scott Tyldesley presented data from the Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) study from Canada, a randomized trial comparing the use of dose-escalated external beam radiation therapy (DE-EBRT) and low-dose-rate-brachytherapy (LDR-B) in men with intermediate- and high-risk prostate cancer. The trial included 122 patients with intermediate-risk disease and 276 patients had high-risk disease by NCCN criteria.
Exclusion criteria included PSA > 40, clinical stage T3b or higher, prior TURP, prostate volume greater than 75cm3, and inability to tolerate anesthesia. Patients received a total of 12 months of androgen deprivation therapy (ADT) with an LHRH antagonist plus a non-steroidal anti-androgen for at least one month as well as whole pelvis EBRT (46Gy) after completion of 8 months of ADT. Patients were then randomized to receive either a conformal 32Gy EBRT boost (DE-EBRT arm) or an iodine-125 LDR boost to a minimum peripheral dose of 115Gy (LDR-B arm). This study found that, over time, LDR-B resulted in a significantly higher relapse-free survival (RFS) with 3-, 5-, 7- and 9-year RFS of 94%, 89%, 86%, and 83% respectively compared to 94%, 77%, 71% and 63% for DE-EBRT (p=0.001). On multivariable analysis controlling for age, percent positive cores, clinical T stage, PSA, risk stratification, number of high-risk features, and Gleason score, receiving LDR-B was associated with a significantly lower likelihood of developing recurrent disease (HR 0.49, 95% CI 0.30-0.80, p=0.004). This difference persisted in both the intermediate- and high-risk groups when analyzed separately. No difference was seen between the LDR-B and DE-EBRT groups with regards to overall survival, prostate cancer-specific survival, or metastasis-free survival. Median overall survival had not been reached at the time of the report of the study, and was estimated to be 13 years on Kaplan-Meier analysis, and thus definitive conclusions regarding the effect of LDR-B on overall survival may be premature at this point. Cumulative 5-year grade 3 urologic toxicity was found to be significantly higher in the LDR-B group compared to the DE-EBRT group (19% vs 5%, p < 0.001). The prevalence of late grade 3 or higher toxicity was noted to be higher in the LDR-B group (8%) compared to the DE-EBRT group (~2%).
In summary, the ASCENDE-RT trial demonstrated a 50% decrease in biochemical relapse with the use of LDR-B in conjunction with ADT and whole pelvis XRT for intermediate- and high-risk prostate cancer when compared to using DE-EBRT with ADT and XRT in patients with intermediate and high-risk prostate cancer. These improved outcomes however come with the cost of higher rates of long-term urologic toxicity.
Presented by Scott Tyldesley, MD, MPA, ABR, FRCPC at the 2015 Genitourinary Cancers Symposium - "Integrating Biology Into Patient-Centric Care" - February 26 - 28, 2015 - Rosen Shingle Creek - Orlando, Florida USA
University of British Columbia, Vancouver, BC Canada
Reported by Timothy Ito, MD medical writer for UroToday.com