Using mpMRI, PSMA, and GRPR PET to Assess Focal Therapy Eligibility and Plan Treatment in Biopsy-proven Low-/Intermediate-risk Prostate Cancer: A Whole-mount Pathology-based Study.

Purpose Focal therapy (FT) is an emerging strategy for selectively ablating prostate cancer (PCa). However, existing challenges comprise conventional techniques inadequately identifying appropriate candidates and insufficient characterization of multifocality and sampling-biases in the biopsy-based trials. We evaluated the value of adding prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) PET to multiparametric MRI (PET/mpMRI) in preoperative assessments for FT, with whole-mount pathology as a comprehensive reference. Methods A total of 38 men with biopsy-proven low-risk/intermediate-risk PCa underwent mpMRI, 68Ga-PSMA, and 68Ga-RM26 PET. Any focal lesion uptake (PETFL) was considered for positive PET results, while PI-RADS for mpMRI interpretation. Index lesion was defined with the highest Gleason score or largest diameter. Detection rates for clinically significant (cs) PCa (lesion-level) and diagnostic performances for localization (segment-level) were assessed. Correct identification of FT-ineligible men (index lesion Grade Group>3 or contralateral csPCa) was documented. Results For detecting the overall 73 csPCa, both 68Ga-PSMA and 68Ga-RM26 PET/mpMRI demonstrated significantly higher detection rates (87.7% and 94.5% vs. 72.6%, P<0.005), as well as higher accuracies for localization (0.87 and 0.90 vs. 0.81, P<0.001) than mpMRI alone. Twenty of 38 (53%) men were confirmed FT-ineligible, of which mpMRI, 68Ga-PSMA, and 68Ga-RM26 PET/mpMRI identified 12 (60%), 20 (100%) and 17 (85%), respectively. Finally, 68Ga-PSMA and 68Ga-RM26 PET/mpMRI identified csPCa lesions in 88.5% and 100% of FT-eligible men, respectively. Conclusions Combining PSMA/GRPR PET and mpMRI facilitates enhanced detection rates as well as higher accuracies for localization in localized PCa. 68Ga-PSMA and 68Ga-RM26 PET/mpMRI may serve as promising imaging tools to improve the preoperative assessments in FT candidates with low-risk/intermediate-risk PCa.