ASTRO 2021: Molecular Imaging with Fluciclovine PET

(UroToday.com) In a special session of the American Society for Radiation Oncology (ASTRO) and Society of Nuclear Medicine and Molecular Imaging (SNMMI) held at the 2021 ASTRO Annual Congress, Dr. Baruch presented on the role of molecular imaging using Fluciclovine PET imaging.

Dr. Baruch began be emphasizing that prostate cancer is the second most common cancer site. Despite initial curative intent treatment, nearly half of patients with have biochemical recurrence. Localization of recurrent disease is critical to guide patient treatment. However, conventional imaging typically fails to localize the site of recurrence. He used examples of two patients with biochemical recurrence following initial radiotherapy. While conventional imaging was negative for each, use of fluciclovine imaging demonstrated distant nodal metastasis. He then emphasized that use the use physiologic and molecularly targeted imaging approaches improves our ability to detect disease and appropriately direct therapy.

Fluciclovine was approved in 2016 by the FDA for the evaluation of patients with biochemical recurrence following prior radiotherapy. Fluciclovine is also known as FACBC, anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid, is a non-natural alicyclic amino acid analogue PET radiotracer. It is not metabolized. In the patient without prostate cancer, fluciclovine has physiologic distribution with the most intense uptake in the liver and pancreas; moderate uptake in the salivary glands, pituitary, muscle, and marrow; and mild uptake in the brain and lung. Upregulated amino acid transporters in prostate cancer, namely LAT1, ASCT1, and ASCT2, perform 1:1 exchange of amino acids which result in a downsloping time-activity curve and support the rationale for early imaging.

Initial data from 2014 published by Dr. Schuster demonstrated high sensitivity but low specificity in the prostate, whereas higher specificity and lower sensitivity in extra-prostatic disease. These research protocols have relied on images at three time points whereas in clinical use, a single imaging time point is used. In real world practice, Dr. Baruch emphasized that fluciclovine had better sensitivity and lower specificity. As with most imaging approaches, the positivity rate of fluciclvine imaging is affected by PSA levels with higher rates of positivity among those with higher PSA levels.

image-0.jpg 

Among patients with low PSA levels (<1 ng/mL), there remained an association between PSA levels and the likelihood of positive fluciclovine scan. Rates of positivity were similar in the prostate / prostate bed (40/113, 35%) and extraprostatic (42/113, 37%).

Dr. Baruch further emphasized that increasing Gleason score was associated with the likelihood of identifying extraprostatic disease.

He then presented a number of cases of patients who underwent local therapy (either with radical prostatectomy or radiotherapy) who presented with biochemical recurrence. When imaged with fluciclovine-PET/CT, these patients were found to have low volume disease in pelvic nodes and the bony skeleton that may not be apparent based on conventional imaging with technetium bone scan and CT scan.

Dr. Baruch then moved to discussing the role of fluciclovine for primary prostate cancer staging in high-risk patients. Among a small cohort of patients (n=28), overall, 18F-fluciclovine PET/CT demonstrated a sensitivity of 66.7% and specificity of 86.4%. At a patient level, nodal disease sensitivity was 40% and specificity was 100%. Among 45 patients with intermediate or high-risk disease who did not have systemic metastasis, the patient level sensitivity of fluciclovine was 61.5% and specific was 89.5%. At a regional level, sensitivity was 57.5% and specificity was more than 95%.

However, Dr. Baruch emphasized issues relating to imaging in proximity to the urinary tract, particularly as ureteral uptake may mimic positive lymph nodes and bladder uptake may obscure the prostate bed. However, not voiding prior to the study may decrease urine secretion and intensity. He suggested that experience may allow for partial volume assessment with identification of tiny nodes with activity higher than the blood pool and approaching marrow. In contrast with some of the technical and interpretive issues with fluciclovine, Dr. Baruch highlighted that PSMA based PET/CT imaging is easier to read and interpret.

Dr. Baruch then switched to discussing how we may apply these imaging approaches to our practices, suggesting that the cat may be out of the bag. While these imaging approaches allow for better localization of tumors and therefore may facilitate the selection of treatment, there is a dearth of data demonstrating that this translates to improved patient outcomes. He emphasized that oligometastatic disease (defined by a limited metastatic burden, 1 to 5 metastases) may have improved outcomes when local treatment in administered in lung, breast, colorectal, kidney, melanoma, and sarcoma tumor sites. In prostate cancer, he highlighted results from the LOCATE trial assessing changes in management: 59% of these patients with biochemically recurrent prostate cancer had a change in management, of which 78% were deemed to be major changes, as a result of fluciclovine imaging.

In the post-prostatectomy biochemical recurrence setting, use of fluciclovine PET/CT, as compared to conventional imaging, demonstrated improved failure free survival at both 3 and 4-years following index, with more than one third (35.4%) of patients having a change in therapy that may be reflected in these improved failure free survival outcomes.

He then highlighted data from Dr. Calais and from Dr. Pernthaler providing direct comparisons of PSMA-based PET/CT imaging and fluciclovine-based approaches. While PSMA outperformed fluciclovine in the identification of extraprostatic disease, work from Dr. Pernthaler suggested that fluciclovine may outperform PSMA for local recurrence. The greatest difference between these approaches can be seen among patients with low PSA levels (<2 ng/mL), with substantially higher detection of distant disease (pelvic and extrapelvic lymph nodes and bony disease) using PSMA-based PET/CT. However, Dr. Baruch emphasized that as the androgen receptor controls the expression of PSMA, long term us of ADT may decrease the sensitivity of PSMA-based PET/CT. Thus, he suggested that fluciclovine may be particularly useful among patients who are having PSA progression while on androgen deprivation therapy.

Presented by: Bital Savir-Baruch, MD, Assistant Professor, Radiology Loyola University Medical Center Maywood, Illinois


Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.

 

 

email news signup