Rais-Bahrami and colleagues have provided an informative overview of the applications of 18F-fluciclovine (FACBC, Axumin®, Blue Earth Diagnostics Ltd) positron emission tomography (PET) for detection and localization of disease in men with biochemically evidence of recurrent prostate cancer [1]. The authors found that the detection rate of metastatic lesions with 18F-fluciclovine PET was overall correlative to prostate-specific antigen (PSA) levels, but that even at low PSA levels of <0.5 ng/mL, 18F-fluciclovine was able to detect a majority of lesions. Additionally, Rais-Bahrami et al importantly found that 18F-fluciclovine PET affected patient management and targeted 18F-fluciclovine radiotherapy planning resulted in improved outcomes. It should be noted that, as with most PET radiopharmaceuticals, the literature regarding use of 18F-fluciclovine in the setting of prostate cancer is limited by small sample sizes and a large heterogeneity of study design, limiting the ability to generalize the findings of specific studies to the disease spectrum as a whole. To this point, the authors of this review evaluated 315 articles, but limited inclusion for data analysis to prospective studies of ≥25 patients with biochemical recurrent prostate cancer. This effort to avoid variability from small sample design, resulted in a review of only 6 relevant articles and 3 conference presentations. Thus, while this review may avoid some bias, the resulting small sample size has remarkable heterogeneity and does not allow for an in-depth analysis of many of the more unanswered questions regarding the utility of 18F-fluciclovine PET in the setting of prostate cancer. For example, within this small data set, there was inconsistent inclusion of: use of a reference standard, androgen deprivation therapy (ADT) status [2, 3], radical prostatectomy [4, 5], radiation therapy [2, 4], Gleason score, and initial nodal status [6, 7]. Additionally, there was heterogeneity in the actual imaging amongst the studies, with included studies starting PET scanning immediately after injection of 18F-fluciclovine [7], 2 minutes [6] after, and with the reminder following the standard 3-5 minute delay post injection. All of these variables have been shown to affect diagnostic outcomes in the literature. Given their self-imposed constraints, the authors made an attempt to correct for the aforementioned variables. Ultimately, however, the disparate nature of each study leads to wildly variable conclusions, such as patient-level detection rates which varied from 26% [6] to 83% [5]. The overall value of 18F-fluciclovine in the setting of biochemical recurrent prostate cancer is well established, but there are many unresolved questions regarding the diagnostic accuracy of 18F-fluciclovine PET that a more targeted review and thoughtful approach to the literature inclusion may reveal. Some areas of uncertain utility for 18F-fluciclovine include: PET-MRI in the setting of prostate-intact prostate cancer [8], 18F-fluciclovine PET for osseous metastatic disease [9], and the continuing applicability of 18F-fluciclovine in the United States with the recent FDA approval of 68Ga PSMA-11 [10]. This last point is particularly pertinent given that the two studies that the review article included that compared 68Ga PSMA-11 to 18F-fluciclovine [6, 7] came to vastly different conclusions regarding the comparative accuracy of 18F-fluciclovine PET. For 18F-fluciclovine to maintain its role in the United States as the de facto molecular imaging agent for biochemical prostate cancer, more targeted analysis must be performed to assure the molecular imager and ordering physicians of its relevancy.
References
Rais-Bahrami S, Efstathiou JA, Turnbull CM, Camper SB, Kenwright A, Schuster DM, et al. (18)F-Fluciclovine PET/CT performance in biochemical recurrence of prostate cancer: a systematic review. Prostate Cancer Prostatic Dis. 2021.
Scarsbrook AF, Bottomley D, Teoh EJ, Bradley KM, Payne H, Afaq A, et al. Effect of (18)f-fluciclovine positron emission tomography on the management of patients with recurrence of prostate cancer: results from the FALCON trial. Int J Radiat Oncol Biol Phys. 2020;107:316–24.
Jani A, Schreibmann E, Goyal S, Raghuveer H, Hershatter B, Rossi PJ, et al. Initial report of a randomized trial comparing conventional- vs conventional plus fluciclovine ((18)F) PET/CT imaging-guided post-prostatectomy radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2020;108:1397.
Nanni C, Zanoni L, Pultrone C, Schiavina R, Brunocilla E, Lodi F, et al. (18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial. Eur J Nucl Med Mol Imaging. 2018;43:1601–10.
Schuster DM, Nieh PT, Jani AB, Amzat R, Bowman FD, Halkar RK, et al. Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial. J Urol. 2014;191:1446–53.
Calais J, Ceci F, Eiber M, Hope TA, Hofman MS, Rischpler C, et al. (18)F-fluciclovine PET-CT and (68)Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncol. 2019;20:1286–94.
Pernthaler B, Kulnik R, Gstettner C, Salamon S, Aigner RM, Kvaternik H. A prospective head-to-head comparison of 18F-fluciclovine with 68Ga-PSMA-11 in biochemical recurrence of prostate cancer in PET/CT. Clin Nucl Med. 2019;44:e566–e573.
Galgano SJ, McDonald AM, Rais-Bahrami S, Porter KK, Choudhary G, Burgan C, et al. Utility of (18)F-Fluciclovine PET/MRI for staging newly diagnosed high-risk prostate cancer and evaluating response to initial androgen deprivation therapy: a prospective single-arm pilot study. AJR Am J Roentgenol. 2020;62:11N.
Chen B, Bathala TK, Xu G, Teyateeti A, Chapin BF, Tang C, et al. Comparison of diagnostic utility of fluciclovine PET/CT versus pelvic multiparametric MRI for prostate cancer in the pelvis in the setting of rising PSA after initial treatment. Clin Nucl Med. 2020;45:349–55.
FDA Approves First PSMA-Targeted PET Drug. J Nucl Med. 2021;62:11N.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Parent, E.E. Letter regarding “18F-Fluciclovine PET/CT performance in biochemical recurrence of prostate cancer: a systematic review”. Prostate Cancer Prostatic Dis 24, 944–945 (2021). https://doi.org/10.1038/s41391-021-00420-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41391-021-00420-6