Abstract
PurposeThe study aimed to evaluate the effect of androgen deprivation therapy (ADT) on PSMA imaging and its correlation to the PSA concentration by comparing qualitative and quantitative parameters: SUVmax, SUVmean, PSMA-derived tumor volume (PSMA-TV), total lesion PSMA (TL-PSMA) and molecular imaging (mi)PSMA score.MethodsRetrospective analysis of 21 therapy-naïve patients with oligometastatic prostate cancer (median age 70 years) who underwent either [68Ga]Ga-PSMA-11-PET/CT or -PET/MRI before initiation of (T1) as well as during ADT (T2). The median duration of ADT was 155 days (range 61–289 days). All lesions were analyzed using several qualitative and quantitative PET parameters.ResultsA total of 109 PSMA-positive lesions (24 intraprostatic, 56 lymphonodal and 29 osseous) were visually detected at any of the examinations, while at T2, two new bone lesions were detected in one patient. During ADT, all patients experienced a decrease in their PSA level (median: 29.1 before vs. 0.71 after; p < 0.001). During long-term ADT, a relevant decrease in lesion count occurred, especially in patients with a T2 PSA value < 1 ng/ml (median: 4 vs. 0.9; p = 0.007) and PSMA expression, which resulted in miN- and/or miM-downstaging in 11 patients (52.7%).All analyzed PET parameters correlated strongly with each other. The PSA level at T2 correlated modestly with the decrease in PSMA expression and its derived volumes.ConclusionPost-ADT scans detected, especially in patients with a residual PSA < 1 ng/ml, fewer PSMA-positive lesions with overall lower PSMA expression, regardless of primary tumor site or metastatic sites. None of the PET parameters has proven to be superior, as they all correlated modestly with the PSA value at T2. Thus, the simply acquirable miPSMA score seems to be the most suitable for evaluating the effect of ADT on PSMA expression.
Highlights
Prostate cancer (PCa) is the world’s most common cancer in men [1]. [68Ga]Ga-labeled Prostate-specific membrane antigen (PSMA) ligands have become state of the art in molecular imaging of PCa in primary and recurrent diseases as well as in therapy monitoring [2,3,4,5,6].In high-risk or oligometastatic situations, therapy includes androgen deprivation therapy (ADT) and Hoberück et al EJNMMI Res (2020) 10:135 radiation therapy [7, 8]
As PSMA-based imaging becomes increasingly important for planning local ablative therapy, the influence of ADT on PSMA expression is of high relevance [14]
Patients Twenty-one therapy-naïve, oligo-metastasized, biopsy-proven patients with prostate cancer with a median age of 70 years who were foreseen for local ablative radiotherapy underwent [68Ga]Ga-PSMA-11PET for primary staging before the start of androgen deprivation therapy
Summary
Prostate cancer (PCa) is the world’s most common cancer in men [1]. [68Ga]Ga-labeled PSMA ligands have become state of the art in molecular imaging of PCa in primary and recurrent diseases as well as in therapy monitoring [2,3,4,5,6].In high-risk or oligometastatic situations, therapy includes androgen deprivation therapy (ADT) and Hoberück et al EJNMMI Res (2020) 10:135 radiation therapy [7, 8]. Prostate cancer (PCa) is the world’s most common cancer in men [1]. [68Ga]Ga-labeled PSMA ligands have become state of the art in molecular imaging of PCa in primary and recurrent diseases as well as in therapy monitoring [2,3,4,5,6]. As PSMA-based imaging becomes increasingly important for planning local ablative therapy, the influence of ADT on PSMA expression is of high relevance [14]. On a cellular level, activated androgen receptors downregulate folate hydrolase 1 (FOLH1) gene expression. As the PSMA promoter and PSMA enhancer are located within FOLH1, its downregulation results in decreased PSMA expression. ADT reduces androgen receptor activation and reverses FOLH1 downregulation, leading to higher PSMA expression [15]
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