(UroToday.com) The 2025 ASTRO annual meeting featured a prostate cancer radiation toxicity session and a presentation by Dr. P. Travis Courtney discussing acute toxicity following dose-escalated MRI-guided stereotactic body radiotherapy versus adapted dose-painted MRI-guided stereotactic body radiotherapy. The MIRAGE trial (NCT04384770) demonstrated improved acute genitourinary and gastrointestinal toxicities in patients with prostate cancer treated with aggressive planning target volume (PTV) margin reduction using MRI-guided stereotactic body radiotherapy.1
It is unknown whether adaptive dose painting (increasing dominant intraprostatic lesion dose, decreasing the PTV dose) can maintain similar toxicity as compared with homogenous, dose-escalated prostate stereotactic body radiotherapy, as used on MIRAGE. Dr. Courtney and colleagues compared acute toxicity between patients receiving MRI-guided stereotactic body radiotherapy on MIRAGE and patients receiving adaptive, dose-painted MRI-guided stereotactic body radiotherapy on the HEATWAVE trial (NCT06067269).
MIRAGE enrolled patients with localized prostate cancer of any NCCN risk group and utilized non-adaptive, MRI-guided stereotactic body radiotherapy with a PTV dose of 40 Gy in 5 fractions. HEATWAVE is enrolling patients with NCCN unfavorable intermediate risk prostate cancer (n = 106) and utilizes 5-fraction adaptive, dose-painted MRI-guided stereotactic body radiotherapy with clinical target volume (CTV), PTV, and dominant intraprostatic lesion doses of 38 Gy, 36.25 Gy, and 50 Gy, respectively. Both trials used 2mm PTV margins. While the primary endpoint is the efficacy of concomitant apalutamide monotherapy, a pre-specified secondary endpoint is acute toxicity, particularly compared to standard MRI-guided stereotactic body radiotherapy. Acute (<90 days from stereotactic body radiotherapy) physician-scored genitourinary and gastrointestinal CTCAE toxicity and patient-reported outcomes (IPSS and EPIC-26 bowel) were compared between the two trials with Fisher’s test.
The MIRAGE cohort included 78 patients, and the HEATWAVE cohort included 23 patients. Similar proportions of patients took urinary medications at baseline (HEATWAVE 17% versus MIRAGE 37%, p = 0.08) and had pre-existing gastrointestinal comorbidities (HEATWAVE 22% versus MIRAGE 14%, p = 0.51). Physician-scored acute grade 2+ genitourinary toxicity rates were significantly higher in HEATWAVE (70% versus 24%, p < 0.01), as were acute 2+ gastrointestinal toxicity rates (17% versus 0%, p < 0.01). Rates of clinically significant decreases in EPIC-26 bowel scores (=12) were not significantly different between HEATWAVE and MIRAGE at 1 (17% versus 30%, p = 0.29) or 3 months (9% versus 24%, p = 0.14). Rates of clinically significant increases in IPSS (n = 15) were not significantly different between HEATWAVE and MIRAGE at 1 (13% versus 7%, p = 0.39) or 3 months (4% versus 8%, p = 1):
Comparison of plan dosimetry did not reveal any dosimetric differences between the two groups.
Dr. Courtney concluded his presentation discussing acute toxicity following dose-escalated MRI-guided stereotactic body radiotherapy versus adapted dose-painted MRI-guided stereotactic body radiotherapy with the following take-home points:
- Patients receiving adaptive, dose-painted MRI-guided stereotactic body radiotherapy had higher physician-scored acute genitourinary and gastrointestinal toxicity than those receiving non-adaptive, homogeneous MRI-guided stereotactic body radiotherapy. However, patient-reported outcomes were similar
- Given that similar planning constraints were used and met for both trials, the etiology of this increased acute toxicity is unclear, though likely related to currently unmeasured dosimetric endpoints
- CTV/PTV dose-reduction alone may not lead to lower toxicity, even with adaptive radiotherapy, when using extremely dose-escalated dominant intraprostatic lesion boosts
- Further investigation is warranted as the trial continues to enroll
Presented by: P. Travis Courtney, MD, MAS, UCLA David Geffen School of Medicine/UCLA Medical Center, Los Angeles, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting, San Francisco, CA, Sat, Sept 27 – Wed, Oct 1, 2025.
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