1187 - Stereotactic Ablative Radiotherapy for High-Risk Prostate Cancer — Long Term Results of a Prospective Multi-Level MRI-Based Dose Escalation Trial

05:20pm - 05:25pm ET

Room 256

Presenter(s)

Akrita Bhatnagar, MD, PhD - UTSW, Dallas, TX

A. Bhatnagar¹, N. B. Desai², A. Garant¹, E. Olayinka¹, L. Robles¹, Y. Lotan³, C. Ahn⁴, R. Shah⁵, C. Roehrborn³, R. D. Timmerman¹, and R. Hannan¹; ¹Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ²University of Texas Southwestern Medical Center, Dallas, TX, ³Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, ⁴Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, ⁵University of Texas Southwestern, Dallas, TX

Purpose/Objective(s): Radiation dose intensification improves oncologic outcomes in men with high-risk prostate cancer (HR-PCa). We conducted a prospective phase I trial to determine the safety, feasibility, maximal tolerated dose (MTD) of ultra-hypofractionated, multi-level MRI-guided dose escalation delivered in 5 fractions using stereotactic ablative radiotherapy (SAbR).

Materials/Methods: In this single-institution trial, men with HR-PCa (grade group =4, PSA >20 ng/mL, or cT3-cT4) and at least one well-defined intraprostatic lesion on multiparametric MRI (mpMRI) were enrolled into four sequential dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Subsequent cohorts escalated nodal dose to 25 Gy and intraprostatic lesion dose to 52.5 Gy and then 55 Gy. Escalation followed a rule-based design with 7–15 patients per cohort and a 90-day dose-limiting toxicity (DLT) window. All patients received peri-rectal hydrogel spacer, intraprostatic fiducial markers, and planned 2 years of androgen deprivation therapy. The primary endpoint was determination of the MTD, defined as a 90-day acute DLT rate <33%. DLT was defined as CTCAE v4.0 grade =3 treatment-related toxicity. Secondary endpoints included acute and late genitourinary (GU) and gastrointestinal (GI) toxicity, biochemical progression-free survival (bPFS), distant metastasis-free survival (DMFS), and overall survival (OS).

Results: 57 of 63 enrolled patients were evaluated. Dose escalation was completed through all cohorts without observing any DLTs. With a median follow-up of 72 months, acute grade 2 GU and GI toxicity occurred in 22% and 15% of patients, respectively. Late grade 2 GU and GI toxicity occurred in 31% and 12%, respectively. Late grade 3 GU toxicity occurred in 5% of patients; no grade =3 GI toxicity was observed. Six-year Kaplan–Meier bPFS, DMFS, and OS were 94%, 95%, and 79%, respectively. Four patients developed biochemical recurrence at 18, 34, 36, and 84 mos (cohorts 1, 3, 3, and 2), of which 3 were found to have bone metastases on imaging, confirming distant failure. Prostate biopsy was performed in one of these patients and demonstrated no evidence of intraprostatic disease. Two additional patients underwent post-SAbR prostate biopsy and no local intraprostatic failures were found.

Conclusion: Multi-level MRI-guided ultra-hypofractionated SAbR for HR-PCa was safely delivered up to 47.5 Gy to the prostate, 55 Gy to intraprostatic lesions, and 25 Gy to pelvic lymph nodes in 5 fractions. Six-year biochemical control was 93% with acceptable late GU and minimal GI toxicity, and no confirmed intraprostatic local failures. This regimen warrants prospective phase II/III evaluation for intensified local therapy in high-risk disease. Ongoing spatial transcriptomic analyses of paired pre- and post-treatment specimens aim to elucidate biological correlates of response to multi-level dose escalation.