Fifteen-year results from the phase III ASCENDE-RT trial in patients with intermediate- and high-risk localized prostate cancer receiving androgen-deprivation therapy (ADT) and pelvic external-beam radiotherapy (EBRT) show no significant overall survival advantage with a prostate brachytherapy boost vs an EBRT boost, with a signal toward improved prostate cancer–specific survival that was sensitive to challenges in determining cause of death, according to findings presented by Scott Tyldesley, MD, FRCPC, of BC Cancer Vancouver, at the 2026 ASCO Genitourinary (GU) Cancers Symposium.1
Scott Tyldesley, MD, FRCPC
“Although prostate cancer was the single most common cause of mortality in ASCENDE-RT, our results suggest that even large improvements in [biochemical no evidence of disease], such as those demonstrated with [prostate brachytherapy boost in the 10-year analysis], 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,” the investigators wrote.
Study Details
As Dr. Tyldesley explained, biochemical recurrence after local therapy can lead to patient anxiety and additional treatments such as ADT, which carry side effects, quality-of-life burdens, and cost implications—despite not always improving survival. He noted that when ASCENDE-RT was conceived in 2000, it was generally understood that radiotherapy dose escalation could improve biochemical disease–free survival, that combining ADT with radiotherapy benefited overall survival in higher-risk patients, and that low–dose-rate (LDR) brachytherapy offered a way to safely deliver higher prostate radiation doses—ideas that helped form the nidus for trials like this one.
ASCENDE-RT evaluated dose-escalation strategies in men with localized prostate cancer and intermediate-risk (≥ 1 of: Gleason score 7, prostate-specific antigen [PSA] 10–20 ng/mL, or clinical stage cT2b) or high-risk (≥ 1 of: Gleason score ≥ 8, PSA > 20 ng/mL, or clinical stage cT3a; those with cT3b/T4 disease or PSA > 40 ng/mL were excluded) features. Eligible patients had histologically confirmed nonmetastatic disease, an Eastern Cooperative Oncology Group performance status score of 0 to 2, fitness for anesthesia, and an estimated life expectancy of at least 5 years.
All patients received 12 months of ADT and pelvic EBRT to 46 Gy in 23 fractions. They were then randomly assigned to either a high-dose conformal EBRT boost to 78 Gy in 39 total fractions (including a 32 Gy boost in 16 fractions; n = 200) or an LDR brachytherapy boost with implantation of iodine-125 radioactive seeds to 115 Gy (n = 198).
The median age was 68 years—“slightly younger than [what] we would normally see,” according to Dr. Tyldesley; 69.3% of patients had high-risk disease, and most intermediate-risk patients had unfavorable features. Overall, 93% received their assigned treatment.
Prior analyses showed that the trial met its primary endpoint, with 10-year freedom from biochemical failure rates of 85% with a brachytherapy boost vs 67% with an EBRT boost—a statistically significant difference, although no differences in secondary survival endpoints were observed.2 The current report evaluated 15-year survival outcomes.
Overall survival was assessed using the Kaplan-Meier method and Cox modeling, and cumulative incidence of death from prostate cancer (CIDPCa) was analyzed using competing-risks methods with Fine and Gray modeling. Cause of death was determined from follow-up through 10 years and, thereafter, from registry data supplemented by medical records. The primary CIDPCa analysis included only deaths definitively attributed to prostate cancer or recorded as such in the registry, with unknown causes not assigned to prostate cancer; in a sensitivity analysis, deaths with unknown cause were classified as prostate cancer deaths.
Key Findings
At the time of analysis, 54% of patients had died. Prostate cancer was the most common cause of death (16%; includes two grade 5 toxicities in the brachytherapy arm), followed by other cancers and other known noncardiovascular causes (both 12%), cardiovascular causes (9%), and unknown causes (4%).
No statistically significant difference in overall survival was observed between the brachytherapy and EBRT boost groups. The 15-year overall survival rate was 60% with brachytherapy vs 55% with EBRT (univariate P = .8), with a multivariable hazard ratio (HR) of 1.02 (P = .908). Addressing whether a larger survival benefit may have been missed, Dr. Tyldesley stated, “I think it is unlikely that there would be a more than 10% difference at 15 years based on these data….”
In the primary analysis of CIDPCa, outcomes appeared to favor the brachytherapy boost, with a 15-year rate of 8.6% vs 16.4% with the EBRT boost (univariate P = .007), corresponding to an absolute difference of 7.8%. This difference was found to remain significant on multivariable analysis (HR = 0.52; P = .012).
Based on the sensitivity analysis, the between-arms difference was attenuated and no longer statistically significant due to a higher number of deaths from unknown causes in the brachytherapy arm, according to Dr. Tyldesley. The 15-year rate was 14.3% with brachytherapy vs 19.4% with EBRT (univariate P = .067; multivariable HR = 0.70, P = .109), representing an absolute difference of 5.1%.
The Findings in Context
Regarding limitations, Dr. Tyldesley noted that overall survival and death from prostate cancer were secondary endpoints, and the study was not designed to detect differences or include a prespecified statistical framework for those analyses. He also highlighted a common challenge in prostate cancer trials, stating that “sometimes it’s difficult to ascertain the cause of death in men as they age.”
Beyond these limitations, Dr. Tyldesley highlighted how changes in contemporary practice since the conception of ASCENDE-RT may influence the interpretation of its findings. He noted that role of nodal radiotherapy was uncertain at the time and “remains questioned, particularly in intermediate-risk patients.” Radiotherapy fractionation has also shifted, with conventional fractionation EBRT now rarely used and greater adoption of moderate hypofractionation and ultra-hypofractionation; however, “whether that would change the main conclusions,” he said, “I think is unlikely.” Contemporary practice also includes delivery of higher-dose EBRT to dominant intraprostatic lesions, which has been associated with improved biochemical control and “would potentially alter the findings if one duplicated this trial with a [dominant intraprostatic lesion] boost,” he added.
In addition, among patients receiving radiotherapy, the recommended duration of ADT has changed in high-risk prostate cancer—from 12 months in this trial to at least 18 months—which “may have implications on the biochemical outcomes,” Dr. Tyldesley stated. He also noted that some patients with very high–risk disease now receive androgen receptor pathway inhibitor intensification.
In conclusion, 15-year findings from ASCENDE-RT indicate no statistically significant difference in overall survival between the arms, “although we can’t rule out a difference of 5% or even 10% with these data,” Dr. Tyldesley stated. He added that any apparent reduction in death from prostate cancer with brachytherapy remains “of borderline significance given the number of times we’ve looked at it and the sensitivity analysis.”
Dr. Tyldesley explained that the results may inform targets for overall survival and CIDPCa in future trials and underscore the importance of selecting patients with lower competing risks of death. The ongoing CCTG-PR24 trial comparing ultra-hypofractionated radiotherapy and brachytherapy boost “will hopefully answer” whether these approaches provide comparable outcomes in the coming years.
DISCLOSURE: Dr. Tyldesley has received honoraria from Ipsen, TerSera, and Tolmar; and has received reimbursement for travel expenses from Tolmar.
REFERENCES
1. Tyldesley S, Pai HH, McKenzie MR, et al: Fifteen-year survival analysis from the ASCENDE-RT randomized trial of external beam boost versus brachytherapy boost in localized prostate cancer. 2026 ASCO GU Cancers Symposium. Abstract 306. Presented February 26, 2026.
2. Oh J, Tyldesley S, Pai H, et al: An updated analysis of the survival endpoints of ASCENDE-RT. Int J Radiat Oncol Biol Phys 115:1061-1070, 2023.
EXPERT POINT OF VIEW
Discussing the 15-year survival analysis from the ASCENDE-RT trial of prostate brachytherapy boost vs external-beam radiotherapy (EBRT) boost in patients with intermediate- and high-risk localized prostate cancer receiving androgen-deprivation therapy (ADT) and EBRT, invited discussant Bridget F. Koontz, MD, FASTRO, of AdventHealth Cancer Institute, Orlando, congratulated the investigators for their “really impressive series of studies” and placed the findings in the broader context of radiation dose escalation strategies and their uncertain impact on long-term survival.1
Bridget F. Koontz, MD, FASTRO
At 15 years, “now we know there still is no [overall] survival benefit [with the brachytherapy boost],” Dr. Koontz said, reinforcing findings previously observed at 10 years.2 Although the primary cumulative incidence of death from prostate cancer (CIDPCa) analysis—in which deaths from unknown causes were not classified as prostate cancer deaths—suggested an improvement, she noted that the presented graph’s reduced y-axis “means the number of events is not as high as you might think.” She also pointed out that two treatment-related deaths in the brachytherapy arm were included as prostate cancer deaths.
Dr. Koontz then addressed how these findings apply in current practice, noting that ASCENDE-RT used standard methods for EBRT boost delivery, whereas newer approaches are now available. “So it may be that the toxicity issue really raises its head as the main challenge in adding brachytherapy,” she said. At the same time, however, she noted that brachytherapy techniques have also evolved, with data suggesting that high–dose-rate (HDR) boost may offer similar efficacy with better quality of life compared with low–dose-rate approaches, allowing for a continued role for brachytherapy in current practice.3,4
Settings in which brachytherapy boost may be considered were also highlighted by Dr. Koontz. A retrospective analysis comparing EBRT vs HDR brachytherapy as boost techniques in high- and very high–risk disease showed results similar to ASCENDE-RT, she stated, with improvements in biochemical progression–free, metastasis-free, and disease-specific survival associated with brachytherapy, and near significance for overall survival; a “substantial survival benefit” was observed in the very high–risk group.5 In addition, she said that “brachytherapy boost is an important consideration which may allow us to reduce the length of ADT,” based on randomized data of high-risk patients receiving brachytherapy and EBRT showing similar cancer-related outcomes with 6 vs 30 months of ADT and “very low” biochemical progression in either arm.6
In conclusion, Dr. Koontz noted that ASCENDE-RT reiterates that “radiotherapy continues to be a highly effective curative treatment for prostate cancer.” She added that “in intact high-risk prostate cancer, brachytherapy boost may be of benefit in young men with anticipated longevity, [in those with] very high–risk localized disease, and in reducing ADT exposure.”
DISCLOSURE: Dr. Koontz has held a leadership role with Rythera Therapeutics; has stock or other ownership interests with Rythera Therapeutics; has received honoraria from Novartis; has held a consulting or advisory role with Blue Earth Diagnostics, Fuse Oncology, Myriad Genetics, and Novartis; has received research funding from Sumitomo Pharma Oncology; and has patents, royalties, or other intellectual property with Demos Medical Publishing.
REFERENCES
1. Tyldesley S, Pai HH, McKenzie MR, et al: Fifteen-year survival analysis from the ASCENDE-RT randomized trial of external beam boost versus brachytherapy boost in localized prostate cancer. 2026 ASCO GU Cancers Symposium. Abstract 306. Presented February 26, 2026.
2. Oh J, Tyldesley S, Pai H, et al: An updated analysis of the survival endpoints of ASCENDE-RT. Int J Radiat Oncol Biol Phys 115:1061-1070, 2023.
3. Crook J, Moideen N, Arbour G, et al: A randomized trial comparing quality of life after low-dose rate or high-dose rate prostate brachytherapy boost with pelvic external beam radiation therapy. Int J Radiat Oncol Biol Phys 120:59-68, 2024.
4. Crook J, Cheng J-C, Arbour G, et al: A randomized comparison of high-dose-rate and low-dose-rate prostate brachytherapy combined with external beam radiation therapy for unfavorable prostate cancer: Efficacy results after median follow-up of 74 months. Int J Radiat Oncol Biol Phys 123:195-203, 2025.
5. Visus I, Jablonska PA, Martínez I, et al: Improved metastasis-free survival without added toxicity in high- and very high-risk prostate cancer: External beam radiotherapy alone versus in combination with HDR brachytherapy boost. Radiother Oncol 214:111274, 2026.
6. Yorozu A, Namiki M, Saito S, et al: Trimodality therapy with iodine-125 brachytherapy, external beam radiation therapy, and short- or long-term androgen deprivation therapy for high-risk localized prostate cancer: Results of a multicenter, randomized phase 3 trial (TRIP/TRIGU0907). Int J Radiat Oncol Biol Phys 118:390-401, 2024.
