3282 - PSA Kinetics and Functional MRI as Complementary Biomarkers of Response after MR-Guided Focal Boost Radiotherapy for High-Risk Prostate Cancer

Purpose/Objective(s): High-risk prostate cancer remains at substantial risk of local recurrence despite dose-escalated radiotherapy. MR-guided radiotherapy (MRgRT) enables precise visualization of dominant intraprostatic lesions (DILs) and real-time adaptive planning, allowing hypofractionated DIL-targeted dose escalation. We report prospective outcomes from a single-center study assessing feasibility, toxicity, early oncologic control, and PSA kinetics in relation to functional MRI response.

Materials/Methods: Patients with D’Amico high-risk prostate cancer treated with neoadjuvant androgen deprivation therapy (ADT) followed by MRgRT were prospectively enrolled. DILs were defined on multiparametric MRI (T2-weighted and diffusion-weighted imaging/apparent diffusion coefficient [ADC]) and deformably registered to planning images with a 3-mm margin. Online adaptive planning and intrafraction motion monitoring were performed at each fraction. The prostate and proximal seminal vesicles received 54 Gy in 12 fractions (BED2 = 175 Gy), with a simultaneous integrated boost to the DIL to 56.2 Gy (BED2 = 187 Gy). Acute genitourinary (GU) and gastrointestinal (GI) toxicities were graded using CTCAE v5.0. Biochemical disease-free survival (bDFS) was defined by Phoenix criteria. Functional imaging response was defined as a post-treatment increase in ADC within the DIL. PSA kinetics, including nadir, time to nadir, and early decline, were analyzed and correlated with imaging response. Outcomes were compared with a historical cohort without focal boost.

Results: Sixty-seven patients were included (median age 74 years; median PSA 20.9 ng/mL; median follow-up 24.5 months); all received neoadjuvant ADT. Acute grade =2 GU and grade 1 GI toxicities occurred in 38% and 22%, with no grade =3 events. Mean IPSS increased by 10.5 points within 3 months in 75% of patients, then returned to baseline. The bDFS rate was 91.2%. Among 52 patients with evaluable post-treatment MRI, 40 (76.9%) showed functional imaging response. PSA kinetics were favorable, with a median PSA nadir of 0.03 ng/mL at 8.2 months and a 59% median reduction at 3 months. Patients with imaging response had a greater PSA decline than non-responders (p = 0.02). Compared with the historical cohort, acute toxicity and quality-of-life outcomes were similar, while early local control remained excellent with DIL boosting.

Conclusion: MR-guided hypofractionated radiotherapy with a simultaneous integrated boost to the DIL achieved excellent biochemical control with acceptable, largely transient toxicity. PSA kinetics were associated with functional MRI changes, suggesting measurable biological effects of DIL-targeted dose escalation even with neoadjuvant ADT. PSA kinetics and functional MRI may serve as complementary, noninvasive biomarkers for early treatment response in precision radiotherapy.