(UroToday.com) The 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting held in Washington, DC between September 29th and October 2nd, 2024, was host to a prostate cancer treatment intensification session. Dr. Juanita Crook presented the efficacy results of a randomized trial comparing low- and high-dose rate brachytherapy, combined with external beam radiotherapy, for intermediate- or high-risk prostate cancer.
Dr. Crook noted that the radiation dose plays an important role in the curative treatment of prostate cancer. There is level one evidence that a low-dose rate (LDR) brachytherapy boost to external beam radiotherapy (78 Gy in 39 fractions) significantly improves biochemical progression-free survival in unfavorable intermediate- and high-risk prostate cancer patients.1 Dr. Crook and colleagues hypothesized that a single fraction of 15 Gy high-dose rate (HDR) brachytherapy may provide the same benefit while minimizing the impact on quality-of-life outcomes.
This was a randomized phase III trial of unfavorable intermediate- or high-risk prostate cancer patients planned for radiotherapy. All patients were required to have negative conventional imaging and be suitable for brachytherapy (volume <60 cc, IPSS score <16, adequate results on a voiding study). All patients were planned for external beam radiotherapy (46 Gy in 23 fractions) + ADT and were randomized to either an HDR boost (15 Gy x 1 [Ir-192]) or an LDR boost (110 Gy [I-125]).
The primary study endpoint was quality-of-life outcomes, which have previously been published in the International Journal of Radiation Oncology, Biology, Physics in 2024.2 This demonstrated the following:
- IPSS and urinary EPIC domain scores:
- HDR brachytherapy boost patients recover to baseline within 6 months
- LDR boost patients recover to baseline by 18 months
- There was no difference between HDR and LDR urinary quality-of-life from 18 to 60 months
- EPIC bowel domain:
- Both nadir at 12 months
- HDR patients recover to a less than minimally clinically important difference (MCID) by 18 months (no grade 3 events)
- LDR patients maintain >MCID to 60 months (one grade 3 event).
In a post hoc adverse event analysis presented at ASTRO 2023, the study investigators reported that grade 2 GU toxicity was observed in 6.7% and 2.4% of HDR- and LDR-treated patients, respectively. There was one grade 3 GU event in each cohort.
In this presentation, Dr. Crook reported the results of the key efficacy (secondary) endpoints:
- Biochemical failure: nadir PSA + 2
- Biochemical cure: PSA ≤0.2 at 4 years
- Overall survival and biochemical failure-free survival
The two arms were well-balanced for key patient characteristics. The median age was 71 years. 57% of patients had high-risk disease, and the remaining 43% had unfavorable intermediate risk. Gleason Score 8–9 disease was present in 43% of patients. Almost half of patients had cT2a-b disease. The median pre-treatment PSA was 11.6 ng/ml (range: 0.94 – 145 ng/ml).
The median patient follow-up was 73 months. 74% of patients received ADT, for a median duration of 12 months. Overall, 68% of patients received EBRT with VMAT/IMRT (HDR: 74%, LDR: 61%, p=0.06). All patients received image guided-EBRT (HDR: 98% KV + fiducials, 2% cone-beam computed tomography [CBCT]; LDR: 45% KV + fiducials, 55% CBCT).
There were no differences in the proportions of patients with a PSA ≤0.2 ng/ml at 4 years between the two arms (HDR: 81% versus LDR: 83%, p=0.91).
Similarly, there was no difference in biochemical progression-free survival:
No differences in overall survival were observed between the two arms:
The patterns of failure are summarized below:
Dr. Crook concluded her presentation as follows:
- This was a phase III randomized trial comparing HDR to LDR boost and was powered to assess quality-of-life outcomes
- This trial was underpowered for the assessment of efficacy endpoints, but it does suggest that HDR and LDR boost are both associated with equivalent biochemical progression-free survival outcomes at 5 and 8 years.
- HDR and LDR boost both appear to be highly effective for the treatment of unfavorable risk prostate cancer, with 85% biochemical cure (i.e., PSA ≤0.2 ng/ml) at 8 years.
- These results support those from Ascende RT, without grade 3 toxicity for either HDR or LDR boosts
- Future directions will include the evaluation of:
- Long-term quality of life and efficacy outcomes at 10 years
- Predictive factors for distant failure Use of systemic therapy intensification
- HDR versus LDR in the monotherapy settings
Presented by: Juanita Crook, MD, FRCPC, Professor, Department of Radiation Oncology, University of British Columbia, Kelowna, BC
Written by: Rashid Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2024 ASTRO Annual Congress held in Washington, DC between September 29th and October 2nd, 2024
References:- Morris WJ, Tyldesley S, Rodda S, et al. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer. Int J Radiat Oncol Biol Phys. 2017; 98(2):275-85.
- 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. 2024; 120(1):59-68.