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

Simona Malaspina, Otto Ettala, Tuula Tolvanen, Johan Rajander, Olli Eskola, Peter J Boström, Jukka Kemppainen, Simona Malaspina, Otto Ettala, Tuula Tolvanen, Johan Rajander, Olli Eskola, Peter J Boström, Jukka Kemppainen

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.

Keywords: ADT; Androgen deprivation therapy; PET; PSMA; Prostate cancer; [18F]PSMA-1007 PET/CT.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Correlation between baseline PSMA SUVmax and FDG SUVmax in bone lesions
Fig. 2
Fig. 2
Correlation between PSMA ΔSUVmax and FDG SUVmax in bone lesions
Fig. 3
Fig. 3
Box plot for PSMA ΔSUVmax according to FDG SUVmax in bone lesions
Fig. 4
Fig. 4
Correlation between PSMA ΔSUVmax and ΔPSA in bone lesions
Fig. 5
Fig. 5
New PSMA bone uptake on L1 vertebra detected in the [18F] PSMA-1007 PET/CT after ADT. The uptake was not seen in the [18F]FDG PET/CT scan. a Baseline [18F] PSMA-1007 PET/CT. b [18F] PSMA-1007 PET/CT after ADT. c Baseline [18F]FDG PET/CT

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