Background
Phase III RCT (ASCENDE-RT). 398 patients with intermediate- and high-risk localized prostate cancer (PSA 10–40 ng/mL or T2c–T3, Gleason ≤9) randomized between 1998 and 2008 to dose-escalated external beam RT (DE-EBRT: 78 Gy/39 fx IMRT to prostate) vs low-dose-rate (LDR) brachytherapy boost (EBRT 46 Gy + LDR-BT boost, ≥115 Gy to prostate) after 8 months of ADT. This is the first large randomized trial to compare LDR brachytherapy boost vs dose-escalated EBRT alone, demonstrating superior biochemical control with brachytherapy boost.
Interventions and follow up
Arm A: 46 Gy pelvic EBRT + LDR-BT prostate boost (≥115 Gy, I-125 or Pd-103) after 8 months ADT
Arm B: 78 Gy EBRT to prostate + elective nodal RT (dose-escalated IMRT) after 8 months ADT
Primary endpoint: Biochemical relapse-free survival (bRFS)
mFollow up: Median 6.5 year
Arm B: 78 Gy EBRT to prostate + elective nodal RT (dose-escalated IMRT) after 8 months ADT
Primary endpoint: Biochemical relapse-free survival (bRFS)
mFollow up: Median 6.5 year
Results
9-year bRFS: 83% LDR-BT boost vs 62% DE-EBRT, HR 0.36, P<.001
9-year distant metastasis-free survival: 94% LDR-BT vs 91% DE-EBRT — not significant
OS: No significant difference
9-year distant metastasis-free survival: 94% LDR-BT vs 91% DE-EBRT — not significant
OS: No significant difference
Adverse events
Main adverse events: LDR-BT boost: significantly higher late GU toxicity grade 3–5 at 5 years (18% vs 5% for DE-EBRT, P<.001); rectal toxicity grade 3–5: 8% vs 3% (not significant). Urinary retention and urinary irritation substantially higher with LDR-BT in short term. DE-EBRT: lower late GU toxicity, fewer urinary side effects.
Conclusions
LDR brachytherapy boost achieves markedly superior biochemical control compared with dose-escalated EBRT (78 Gy) for intermediate/high-risk prostate cancer, with a 9-year bRFS of 83% vs 62%. However, this biochemical benefit comes at the cost of significantly higher late GU toxicity. OS was not significantly different. The bRFS advantage of the LDR-BT boost likely reflects superior dose escalation (biologically equivalent dose >200 Gy with LDR-BT vs ~78 Gy conventional EBRT).
Key Limitations
Key Limitations: Biochemical relapse-free survival is a surrogate endpoint; no OS benefit demonstrated at median 6.5 years. The substantially higher late GU toxicity (18% grade 3–5) is a significant concern and limits broad adoption of LDR-BT boost. Urinary baseline function must be considered before offering brachytherapy boost. The comparison arm (78 Gy IMRT) may be suboptimal — modern HDR brachytherapy boost trials suggest similar or better outcomes with lower toxicity than LDR-BT boost.
Clinical Context
ASCENDE-RT provides the strongest randomized evidence supporting brachytherapy boost over EBRT alone for intermediate/high-risk prostate cancer. The biochemical control advantage is striking, but the toxicity tradeoff has made LDR-BT boost a specialist option rather than a universal standard. AUA/ASTRO guidelines indicate that brachytherapy boost is an option for intermediate/high-risk patients with good urinary function. HDR brachytherapy boost (2 fractions) is increasingly used as a less-morbid alternative to LDR-BT, with several institutional series showing comparable efficacy and potentially lower urinary toxicity.