1221 - MRI-Guided Risk-Adaptive High Dose-Rate Brachytherapy for Radiorecurrent Prostate Cancer: A Phase II Trial

08:25am - 08:30am ET

Room 253

Presenter(s)

Bryce Thomsen, MD - Brigham and Women's Hospital/Dana Farber Cancer Institute, Boston, MA

B. Thomsen¹, T. C. Harris², I. Buzurovic², K. Y. Shin³, S. Chirmade⁴, R. N. Boyajian⁵, A. M. Kowtoniuk⁶, A. C. Smart², P. F. Orio III⁷, and M. T. King²; ¹Department of Radiation Oncology, Mass General Brigham, Harvard Medical School, Boston, MA, ²Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, ³Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, ⁴Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, ⁵Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, ⁶Brigham and Women's Hospital, Boston, MA, ⁷Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA

Purpose/Objective(s):

Approximately 30% of patients treated with definitive radiotherapy for localized prostate cancer experience biochemical recurrence. Salvage reirradiation offers a curative option, but toxicity is a concern for this population. A risk-adaptive treatment paradigm may balance cancer control and toxicity by delivering whole gland radiation with an MRI-defined dominant intraprostatic lesion (DIL) boost, or focal DIL treatment alone if patients are at higher risk of toxicity. We report the results of a prospective phase II trial evaluating MRI-guided high dose-rate (HDR) brachytherapy with dose escalation to the DIL for radiorecurrent prostate cancer.

Materials/Methods:

Eligible patients had biopsy-proven local failure >30 months after EBRT or brachytherapy, with an MRI-identifiable DIL. All patients underwent a multiparametric MRI simulation prior to brachytherapy. The HDR prescription was 1050 cGy x 2 fractions to the prostate CTV with dose escalation to the DIL + 3 mm margin >115%. For patients with risk factors (poor urinary function, prior brachytherapy), the CTV was the DIL + 5 mm margin. ADT use was at investigator discretion. We hypothesized that the urinary irritative QOL decline would not exceed two times the minimally important difference (MID) measured by EPIC-26 at 2 years from baseline in 30% or more patients. The study had 90.5% power to detect 30% QOL decline exceeding the 2x MID benchmark using a one-sample exact binomial test (one-sided a=0.1). Secondary outcomes included PSA progression, 2-year progression-free survival using the Kaplan-Meier method, and toxicity assessed by CTCAE v4.0. This trial was registered on ClinicalTrials.gov (NCT04545957).

Results: From October 2020 to July 2023, 46 patients were enrolled with a median follow-up of 2.1 years (range: 1.5–2.3) and median age of 73.9 years. The median time after the initial radiation course was 9.7 years (range: 0.04 – 20.2). 39 patients had whole gland treatment, and 7 patients had focal treatment. Median GTV D90 for fractions 1 and 2 were 14.2 Gy (range: 1.27 – 17.0) and 14.0 Gy (range: 12.1 – 20.4), respectively. Among 42 patients with EPIC-26 responses at 2-years, the percentage of patients with QOL decline exceeding 2x MID was 21.4% (9/42), meeting the predefined =30% threshold. The percent of grade =3 genitourinary and gastrointestinal toxicity was 4.3% (2/46). The 2-year PSA progression-free rate was 85.5% (95% CI: 67.1, 94.0).

Conclusion: MRI-guided risk-adaptive HDR brachytherapy with DIL-directed dose escalation met its prespecified quality-of-life endpoint while maintaining low severe toxicity and favorable early biochemical control. By individualizing whole-gland versus focal treatment based on functional and prior treatment risk, this approach demonstrates that reirradiation can be both oncologically effective and tolerable. These findings support risk-adapted MRI-guided HDR as a compelling salvage strategy in appropriately selected patients with radiorecurrent prostate cancer.