Reader Training for the Restaging of Biochemically Recurrent Prostate Cancer Using ¹⁸F-Fluciclovine PET/CT

Abstract

F-Fluciclovine is a novel PET/CT tracer. This blinded image evaluation (BIE) sought to demonstrate that, after limited training, readers naïve to F-fluciclovine could interpretF-fluciclovine images from subjects with biochemically recurrent prostate cancer with acceptable diagnostic performance and reproducibility. The primary objectives were to establish individual readers' diagnostic performance and the overall interpretation (2/3 reader concordance) compared with standard-of-truth data (histopathology or clinical follow-up) and to evaluate interreader reproducibility. Secondary objectives included comparison to the expert reader and assessment of intrareader reproducibility. F-Fluciclovine PET/CT images ( = 121) and corresponding standard-of-truth data were collected from 110 subjects at Emory University using a single-time-point static acquisition starting 5 min after injection of approximately 370 MBq of F-fluciclovine. Three readers were trained using standardized interpretation methodology and subsequently evaluated the images in a blinded manner. Analyses were conducted at the lesion, region (prostate, including bed and seminal vesicle, or extraprostatic, including all lymph nodes, bone, or soft-tissue metastasis), and subject level. Lesion-level overall positive predictive value was 70.5%. The readers' positive predictive value and negative predictive value were broadly consistent with each other and with the onsite read. Sensitivity was highest for readers 1 and 2 (68.5% and 63.9%, respectively) whereas specificity was highest for reader 3 (83.6%). Overall, prostate-level sensitivity was high (91.4%), but specificity was moderate (48.7%). Interreader agreement was 94.7%, 74.4%, and 70.3% for the lesion, prostate, and extraprostatic levels, respectively, with associated Fleiss' κ-values of 0.54, 0.50, and 0.57. Intrareader agreement was 97.8%, 96.9%, and 99.1% at the lesion level; 100%, 100%, and 91.7% in the prostate region; and 83.3%, 75.0%, and 83.3% in the extraprostatic region for readers 1, 2, and 3, respectively. Concordance between the BIE and the onsite reader exceeded 75% for each reader at the lesion, region, and subject levels. Specific training in the use of standardized interpretation methodology for assessment ofF-fluciclovine PET/CT images enables naïve readers to achieve acceptable diagnostic performance and reproducibility when staging recurrent prostate cancer.

Effect of 18F-Fluciclovine Positron Emission Tomography on the Management of Patients With Recurrence of Prostate Cancer: Results From the FALCON Trial

“…11,12 Investigational prostate-specific membrane antigen (PSMA)-based PET tracers such as 68 Ga-PSMA-11 show promising results in the BCR setting, 13 but are yet to be approved in Europe or the United States. 18 F-Fluciclovine is a synthetic amino acid radiotracer that is approved in Europe and the United States for detection of BCR of prostate cancer on account of its established diagnostic performance across a wide PSA range. [14][15][16] Here, we evaluate the clinical benefit of 18 F-fluciclovine PET/CT by assessing the effect on management decisions for men with BCR of prostate cancer under consideration for curativeintent salvage treatment.…”

Understanding and Improving 18F-Fluciclovine PET/CT Reports: A Guide for Physicians Treating Patients with Biochemical Recurrence of Prostate Cancer

“…Of interest, prostate-specific membrane antigen (PSMA) radioligand tracers and 18 F-fluorocholine also appear to exhibit a lack of enhanced uptake by some sclerotic bone lesions in patients with prostate cancer, based on comparisons with 18 F-sodium fluoride [15][16][17]. 18 F-Fluciclovine PET/CT image interpretation is described in detail elsewhere [7,8]. Additionally, interpretation can be studied in an online training module of the Society for Nuclear Medicine and Molecular Imaging.…”

“…Referring and interpreting physicians should know that according to standard 18 F-fluciclovine PET/CT image interpretation methodology [6,7], the principal criterion to diagnose recurrence in the prostate bed of men with intact prostates is diffuse, focal, or multifocal 18 F-fluciclovine uptake visually equal to or greater than bone marrow uptake. When lesions are <1 cm, the principal criterion to diagnose recurrence is 18 F-fluciclovine uptake visually significantly greater than uptake in the blood pool (i.e., approaching that in bone marrow).…”

“…Both referring physicians and imagers can help improve the quality of 18 F-fluciclovine PET/CT reports. Insofar as possible, referring physicians should seek imagers who have had specific training in 18 F-fluciclovine PET/CT acquisition and interpretation [7]. Further, referring physicians should furnish imagers with clinical/laboratory data that will help optimize the study report.…”

“…Many urologists, for instance, have had relatively limited experience with PET, which has not been widely applied in prostate, kidney, or bladder cancers. Further, while standardized procedures exist for 18 F-fluciclovine PET/CT image acquisition [3,6] and image interpretation [6][7][8], no standardized grading system or templates have been introduced for 18 F-fluciclovine PET/CT reporting. us, 18 F-fluciclovine PET/CT reports can vary significantly in format, level of detail, and terminology.…”