PSA and PSMA Kinetics After PSMA-PET and MR Guided Prostate Stereotactic Body Radiation Therapy With Focal Boost: Results From the Phase 2 PROBE Trial.

[PURPOSE] To evaluate prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) kinetics following PSMA-positron emission tomography (PET) and magnetic resonance (MR) guided stereotactic body radiation therapy (SBRT) and short-term androgen deprivation therapy with dominant intraprostatic lesion (DIL) boost in localized prostate cancer.

[METHODS AND MATERIALS] This prespecified analysis from the phase 2 PROBE trial (IRB approval: IEC 900917) included patients with intermediate- or high-risk prostate cancer treated with 5-fraction SBRT (36.25 Gy to prostate; 40 to 42.5 Gy to PSMA/MRI-defined DIL) and 6 months of androgen deprivation therapy. PSA kinetics relied on 3-monthly PSA levels. Longitudinal metabolic response, based on the adapted PET Response Criteria in Solid Tumors, was assessed using 68Ga-PSMA-PET/computed tomography done at SBRT completion, 3 to 6 months, and 9 to 12 months after SBRT completion. Cumulative genitourinary/gastrointestinal toxicities were reported per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

[RESULTS] Thirty enrolled patients (54% intermediate risk, 46% high risk) were included. A PSA <0.1 ng/mL was achieved in 79% of patients at 6 months and 50% at 12 months. The mean maximum standardized uptake value (SUVmax) decreased from 12.2 (range, 4.0-39.6) pretreatment to 3.2 at 3 to 6 months and 1.8 at 9 to 12 months. Complete response (CR) rates increased from 17% at SBRT completion to 48% at 3 to 6 months and 65% at 9 to 12 months. Patients achieving CR at 3 to 6 months reached a lower mean PSA (0.04 vs 0.3 ng/mL, P = .009). Those with PSA <0.1 ng/mL at 6 months were more likely to attain CR at 12 months (76% vs 28%, P = .003). An early standardized uptake value (SUV) "flare" was observed in 4 (14%) patients, resolving by 9 to 12 months. No National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥3 genitourinary/gastrointestinal toxicity was seen.

[CONCLUSIONS] PSMA-PET and MR guided prostate SBRT with DIL boost achieved deep PSA nadirs, gradual PSMA kinetics, and a favorable safety profile. About 80% of patients achieved a PSA <0.1 ng/mL at 6 months, with two-thirds achieving CR by 12 months post-SBRT. Achieving a PSA <0.1 ng/mL could potentially predict PSMA-CR. Early PSMA-CR at 3 to 6 months may predict durable PSA response and warrants further evaluation as a biomarker for risk-adapted strategies in localized prostate cancer.