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

Lucia Zanoni,Lorenzo Bianchi,Riccardo Schiavina,Filippo Lodi,Stefano Fanti,Cristina Nanni,Cristian Vincenzo Pultrone,Antonella Matti,Antonietta D’Errico,Cristina Fonti,Irene Bossert,Riccardo Mei,Eugenio Brunocilla,Lorenzo Maltoni,Michelangelo Fiorentino,Francesca Giunchi

doi:10.3390/cancers13071575

Abstract

Simple SummaryThe role of [18F]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 [18F]Fluciclovine and conventional [11C]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 [18F]Fluciclovine uptake values and pISUP was demonstrated. Overall, the lesion-based performance of PET semiquantitative parameters (SUVmax, Target to background Ratio-TBRs) with either [18F]Fluciclovine or [11C]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.The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]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 [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]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 [18F]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.

Highlights

Prostate cancer (PCa) is one of the most common tumors, with an increasing incidence in elderly men
MRI still have some limitations: it detects less than 30% of International Society of Urological Pathology (ISUP) grade 1 smaller than 0.5 cc and has poor sensitivity for central prostatic gland involvement; it suffers from significant falsepositive (FP) rates in benign prostatic hyperplasia (BPH); despite the use of standardized Prostate Imaging—Reporting and Data System (PIRADSv2) score [8], Multi-parametric Magnetic Resonance Imaging (mpMRI) inter-reader reproducibility remains mild and requires dedicated radiologists
With the present study we aimed to investigate the role of [18F]Fluciclovine Positron Emission Tomography (PET)/CT in the characterization of intra-prostatic lesions in men with high-risk primary PCa scheduled for radical prostatectomy (RP) and pelvic lymph-node dissection (PLND), comparing investigational [18F]Fluciclovine and conventional [11C]Choline Positron Emission Tomography/Computed Tomography (PET/CT) results with the reference standard of pathologic surgical specimen

Summary

Introduction

Prostate cancer (PCa) is one of the most common tumors, with an increasing incidence in elderly men. Multi-parametric Magnetic Resonance Imaging (mpMRI) represents the most useful method for local staging, being able to depict size and extension of disease to adjacent organ and to improve the surgical planning, despite still not sensitive for microscopic extraprostatic-extension (EPE) [5,6]. The use of high field strength (3 Tesla) or functional imaging improves sensitivity and, when combined with clinical data, increases pathological stage prediction [1]. MRI still have some limitations: it detects less than 30% of ISUP grade 1 smaller than 0.5 cc and has poor sensitivity for central prostatic gland involvement; it suffers from significant falsepositive (FP) rates in benign prostatic hyperplasia (BPH); despite the use of standardized Prostate Imaging—Reporting and Data System (PIRADSv2) score [8], mpMRI inter-reader reproducibility remains mild and requires dedicated radiologists

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