The Role of [(18)F]Fluciclovine PET/CT in the Characterization of High-Risk Primary Prostate Cancer: Comparison with [(11)C]Choline PET/CT and Histopathological Analysis

SIMPLE SUMMARY: The role of [(18)F]Fluciclovine Positron Emission Tomography/Computed Tomography (PET/CT) in the characterization of intra-prostatic lesions was evaluated in high-risk primary PCa patients, scheduled for radical surgery, comparing investigational [(18)F]Fluciclovine and conventional [(11)C]Choline PET/CT results with the reference standard of pathologic surgical specimen. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, unblinded, according to a pathology reference mapping. Among 19 pts, 45 malignant and 31 benign lesions were found. The highest SUVmax matched with the lobe of the index lesion in 89% of pts and a direct correlation between [(18)F]Fluciclovine uptake values and pISUP was demonstrated. Overall, the lesion-based performance of PET semiquantitative parameters (SUVmax, Target to background Ratio-TBRs) with either [(18)F]Fluciclovine or [(11)C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70), but still inadequate (AUCs ≤ 0.81) as standalone staging procedure. TBRs (especially with threshold higher than bone marrow) may be complementary to implement malignancy targeting. ABSTRACT: The primary aim of the study was to evaluate the role of [(18)F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [(11)C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the “blinded” prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [(18)F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [(18)F]Fluciclovine or [(11)C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [(18)F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.