PSMA-PET-Guided Intraprostatic Boost in Prostate SBRT (PROBE): A Phase 2 Trial

To assess the safety of using combined Gallium68-prostate-specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) (⁶⁸Ga-PSMA-PET/CT) and multiparametric magnetic resonance imaging (mpMRI) for planning dominant intraprostatic lesion (DIL) boost in prostate stereotactic radiation therapy (SBRT) for dose escalation (PROBE).

Patients with intermediate- or high-risk prostate adenocarcinoma with DIL identified on mpMRI and ⁶⁸Ga-PSMA-PET/CT and suitable for SBRT were enrolled in this phase 2 trial. ⁶⁸Ga-PSMA-PET/CT was fused with mpMRI for gross tumor volume (GTV) delineation. Semiautomatic contouring of DIL was performed using 20% to 90% of the maximum standardized uptake value (SUV_max) (DILx%). Concordance metrics were used to select the DILx% matching closest to GTV_MRI (GTV_PET). Prostate (36.25 Gy), pelvic nodes (25 Gy), GTV_union: GTV_PET ∪ GTV_MRI (40 Gy), and GTV_overlap: GTV_PET ∩ GTV_MRI (42.5 Gy) were planned for 5-fraction SBRT. All patients received androgen deprivation therapy (ADT) for 6 months. The primary endpoint for the present analysis was concordance (volumetric and spatial) between GTV_MRI and GTV_PET. Secondary endpoints included the percentage SUV_max threshold for GTV_PET contouring (%SUV_GTV-PET) and cumulative acute (≤90 days) urinary and gastrointestinal toxicity using Common Terminology Criteria for Adverse Event (CTCAE) v5.0.

Thirty patients (54% intermediate risk, 46% high risk) were enrolled. GTV_MRI and GTV_PET showed strong volumetric correlation (Spearman correlation coefficient ρ = 0.817, 95% CI, 0.64-0.91; P < .001). The median Dice similarity coefficient, Jaccard index, and the mean Hausdorff distance for PET and magnetic resonance imaging boost volumes were 0.56, 0.37, and 2.2, respectively. The median %SUV_GTV-PET was 48% (IQR, 40%-58%). There was an inverse correlation between DIL SUV_max and %SUV_GTV-PET (Spearman correlation coefficient ρ = -0.598, 95% CI lower -0.79, upper -0.29; P < 0.001). Cumulative grade 2 acute urinary and GI toxicity were 13.3% and 6.6%, respectively, with no grade ≥3 toxicities.

Boost volumes on ⁶⁸Ga-PSMA-PET/CT and mpMRI were volumetrically similar, however, with poor spatial concordance. The %SUV_max threshold for GTV_PET contouring correlated inversely with DIL SUV_max and was a median of 48%. Based on the favorable acute toxicity profile, PSMA-PET-guided intraprostatic boost is likely to be safe for dose escalation in prostate SBRT.