Editor's Note: At a recent international oncology conference, Professor Scott Tyldesley from Vancouver, Canada, delivered an oral presentation on behalf of Professor Jim Morris, sharing the 15-year long-term survival analysis of the ASCENDE-RT trial (Abstract No. 306). This study compared the long-term overall survival (OS) and prostate cancer-specific mortality (PCSM) of an external beam radiotherapy (EBRT) boost versus a low-dose-rate (LDR) brachytherapy boost in patients with localized prostate cancer. Oncology Frontier (Mediamedic) has summarized the core academic highlights to share with our readers.01 Study Background and Design: Exploration of Dose Escalation and Radiotherapy Boost Strategies
Biochemical recurrence following local therapy for localized prostate cancer often leads to patient anxiety and triggers subsequent interventions such as androgen deprivation therapy (ADT), thereby impacting quality of life and increasing healthcare costs. However, biochemical recurrence does not necessarily translate directly into overall survival differences. Based on the clinical consensus around the year 2000—that radiotherapy dose escalation improves biochemical progression-free survival (bPFS) and adding ADT to radiotherapy improves OS for high-risk patients—investigators designed and initiated the ASCENDE-RT randomized controlled trial.
The study enrolled patients with intermediate- and high-risk localized prostate cancer. All enrolled patients received 12 months of ADT combined with pelvic radiotherapy (46 Gy in 23 fractions), followed by a 1:1 randomization to receive one of two boost modalities:
- EBRT Boost Group: Received an external beam boost to a total dose of 78 Gy.
- Brachytherapy Boost Group: Received a low-dose-rate (LDR) brachytherapy boost (115 Gy via I-125 seed implantation).
Inclusion criteria required patients to be fit for anesthesia, have a good performance status, and a life expectancy of at least 5 years. Patients with extreme metastasis risk (PSA > 40 ng/mL or clinical stage T3b/T4) were excluded. In the final analysis population, approximately 70% were high-risk and 30% were intermediate-risk, with over 90% of patients strictly receiving their assigned treatments.
02 Previous Data Review: Significant Benefit in Biochemical Progression-Free Survival (bPFS)
Prof. Tyldesley first reviewed the previously reported 10-year follow-up results of the study. Prior data indicated that the brachytherapy boost group demonstrated an absolute benefit of nearly 20% in bPFS (defined by the Houston/Phoenix criteria) compared to the EBRT boost group. However, at the 10-year follow-up mark, no statistically significant differences were observed in metastasis-free survival (MFS) or overall survival (OS) between the two arms. Additionally, the incidence of genitourinary (GU) and gastrointestinal (GI) toxicities was slightly higher in the brachytherapy boost group than in the EBRT boost group.
03 15-Year Follow-Up Update: Overall Survival (OS) and Prostate Cancer-Specific Mortality (PCSM)
This meeting focused on the updated data from this cohort with up to 15 years of follow-up. The first 10 years involved prospective follow-up, while data beyond 10 years were collected retrospectively via registry systems. Currently, the median follow-up has reached 15 years, and over 50% of the patients have died. The primary causes of death were distributed as follows: prostate cancer (16%), other malignancies (12%), cardiovascular diseases (9%), and unknown causes (4%).
- Overall Survival (OS) Data: Whether evaluated via Kaplan-Meier curve analysis or multivariable Cox proportional hazards models, no statistically significant difference in OS was observed between the two groups (multivariable model P > 0.10). At the 15-year follow-up point, the survival curves even crossed and overlapped, indicating that the two boost strategies performed comparably in terms of overall survival.
- Prostate Cancer-Specific Mortality (PCSM) Data: In the primary analysis, the cumulative incidence of PCSM in the brachytherapy boost group was significantly lower than that in the EBRT boost group (8.6% vs. 16%), representing an absolute difference of approximately 8%. Both univariable and multivariable analyses showed this difference to be statistically significant. However, the investigators conducted a sensitivity analysis: when “unknown causes of death” were analyzed under a worst-case scenario (attributing all to prostate cancer deaths), the absolute difference between the two groups narrowed, and statistical significance was lost in both univariable and multivariable models.
04 Clinical Implications and Future Perspectives
Prof. Tyldesley objectively pointed out the limitations of this study: OS and PCSM were only secondary endpoints of the trial, and the study was not initially powered to detect differences in these two metrics. Furthermore, cause-of-death data in the later follow-up period relied heavily on death certificates, introducing a degree of uncertainty.
Looking back over the 25 years since the trial was initiated, clinical practice for prostate cancer has undergone profound changes. Today, the widespread use of PET/CT for precise staging, the optimization of ADT duration for intermediate- and high-risk patients, the application of stereotactic body radiotherapy (SBRT)/ultra-hypofractionation, and focal boost strategies targeting dominant intraprostatic lesions (DIL) provide more options for clinical management.
Conclusion
In summary, the 15-year long-term follow-up of the ASCENDE-RT trial confirms that, compared to an EBRT boost, the LDR brachytherapy boost yields a significant bPFS benefit at 10 years (an 18% absolute difference), but this advantage in biochemical control does not translate into a significant OS improvement at 15 years. Regarding PCSM, the brachytherapy boost group demonstrated a favorable trend, but its statistical significance was sensitive to the method of cause-of-death ascertainment. In the future, prospective clinical trials comparing ultra-hypofractionated radiotherapy with a brachytherapy boost (such as the trial led by Prof. Andrew Loblaw) are expected to provide new evidence-based medical guidance for precise, intensified local therapy in prostate cancer.
