Histologic validation of auto-contoured dominant intraprostatic lesions on [18F] DCFPyL PSMA-PET imaging

•Focal therapy guidelines were SUV ~70% of SUVmax with a ~8 mm margin.•Guided biopsy guidelines were SUV ~80% of SUVmax with a ~5 mm margin.•No dominant intraprostatic lesion missed using both guidelines. PSMA-PET11Prostate-specific membrane antigen positron-emission tomography. has shown good concordance with histology, but there is a need to investigate the ability of PSMA-PET to delineate DIL22Dominant intraprostatic lesion. boundaries for guided biopsy and focal therapy planning. To determine threshold and margin combinations that satisfy the following criteria: ≥95% sensitivity with max specificity and ≥95% specificity with max sensitivity. We registered pathologist-annotated whole-mount mid-gland prostatectomy histology sections cut in 4.4 mm intervals from 12 patients to pre-surgical PSMA-PET/MRI by mapping histology to ex-vivo imaging to in-vivo imaging. We generated PET-derived tumor volumes using boundaries defined by thresholded PET volumes from 1–100% of SUV33Standard uptake value.max in 1% intervals. At each interval, we applied margins of 0–30 voxels in one voxel increments, giving 3000 volumes/patient. Mean and standard deviation of sensitivity and specificity for cancer detection within the 2D oblique histologic planes that intersected with the 3D PET volume for each patient. A threshold of 67% SUV max with an 8.4 mm margin achieved a (mean ± std.) sensitivity of 95.0 ± 7.8% and specificity of 76.4 ± 14.7%. A threshold of 81% SUV max with a 5.1 mm margin achieved sensitivity of 65.1 ± 28.4% and specificity of 95.1 ± 5.2%. Preliminary evidence of thresholding and margin expansion of PSMA-PET images targeted at DILs validated with histopathology demonstrated excellent mean sensitivity and specificity in the setting of focal therapy/boosting and guided biopsy. These parameters can be used in a larger validation study supporting clinical translation.