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.