Flare on [18F]PSMA-1007 PET/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: possible marker of tumor aggressiveness in treatment-naïve metastatic prostate cancer patients

Abstract

Purpose Short-term androgen deprivation therapy (ADT) is known to increase heterogeneously prostate-specific membrane antigen (PSMA) expression. This phenomenon might indicate the potential of cancer lesions to respond to ADT. In this prospective study, we evaluated the flare on [18F]PSMA-1007 PET/CT after ADT in metastatic prostate cancer (PCa). Given that aggressive PCa tends to display FDG uptake, we particularly investigated whether the changes in PSMA uptake might correlate with glucose metabolism. Methods Twenty-five men with newly diagnosed treatment-naïve metastatic PCa were enrolled in this prospective registered clinical trial. All the patients underwent [18F]PSMA-1007 PET/CT immediately before and 3–4 weeks after ADT initiation (degarelix). Before ADT, [18F]FDG PET/CT was also performed. Standardized uptake values (SUV)max of primary and metastatic lesions were calculated in all PET scans. Serum PSA and testosterone blood samples were collected before the two PSMA PET scans. The changes in PSMA uptake after ADT were represented as ΔSUVmax. Results All the patients reached castration levels of testosterone at the time of the second [18F]PSMA-1007 PET/CT. Overall, 57 prostate, 314 lymph nodes (LN), and 406 bone lesions were analyzed. After ADT, 104 (26%) bone, 33 (11%) LN, and 6 (11%) prostate lesions showed an increase (≥ 20%) in PSMA uptake, with a median ΔSUVmax of + 50%, + 60%, and + 45%, respectively. Among the lesions detected at the baseline [18F]PSMA-1007 PET/CT, 63% bone and 46% LN were FDG-positive. In these metastases, a negative correlation was observed between the PSMA ΔSUVmax and FDG SUVmax (p < 0.0001). Moreover, a negative correlation between the ΔSUVmax and the decrease in serum PSA after ADT was noted (p < 0.0001). Conclusions A heterogeneous increase in PSMA uptake after ADT was detected, most evidently in bone metastases. We observed a negative correlation between the PSMA flare and the intensity of glucose uptake as well as the decrease of serum PSA, suggesting that lesions presenting with such flare might potentially be less aggressive. Trial registration NCT03876912, registered 15 March 2019.

Deep learning-based whole-body PSMA PET/CT attenuation correction utilizing Pix-2-Pix GAN

“…Future work is needed to determine whether the described Gen-PET methods would be within reliability metrics for response assessment criteria, such as PERCIST [ 23 ]. However, limited longitudinal data were available in the present study, and the clinical utility of PSMA PET/CT imaging in treatment response assessment is uncertain due to complex biological relationships between PSMA and standard-of-care androgen-deprivation therapies [ 24 ].…”

Effects of novel androgen receptor signaling inhibitors on PSMA PET signal intensity in patients with castrate-resistant prostate cancer: a prospective exploratory serial imaging study

“…It was suggested by clinical studies and case reports that a heterogeneous increase in PSMA ligand uptake on PET can be observed in PCa lesions early after initiation of androgen receptor modulating treatments [9,11,12]. However, this "PSMA are" phenomenon has signi cant inter-and intra-patient variability and was almost exclusively described in castration-sensitive prostate cancer.…”

Effects of novel androgen receptor signaling inhibitors on PSMA PET signal intensity in patients with castrate-resistant prostate cancer: a prospective exploratory serial imaging study

“…It was suggested by clinical studies and case reports that a heterogeneous increase in PSMA ligand uptake on PET can be observed in PCa lesions early after initiation of androgen receptor modulating treatments [ 9 , 11 , 12 ]. However, this “PSMA flare” phenomenon has significant inter- and intra-patient variability and was almost exclusively described in castration-sensitive prostate cancer.…”