Upregulation of PSMA Receptors After Androgen Deprivation Therapy on PSMA PET/CT Imaging in Prostate Cancer

Abstract Purpose Based on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression. Therefore, we hypothesised that ADT improves the performance of PSMA-PET imaging in primary staging of prostate cancer. The purpose of the study was to demonstrate the time course effect of ADT on PSMA uptake in different types of metastatic lesions evaluated with 68Ga-PSMA-11 PET/MRI. Methods Nine men with treatment-naïve prostate cancer were enrolled to a prospective, registered (NCT03313726) clinical trial. A 68Ga-PSMA-11 PET/MRI was performed once before and 3 times post-ADT (degarelix, Firmagon). Change of maximum standardised uptake values (SUVmax) in prostate, lymph nodes, bone metastases, and physiologically PSMA-avid organs were evaluated in a time frame of 1–8 weeks. Results All patients reached castration levels within 10 days, and 50% decrease in prostate-specific antigen (PSA) concentration was observed 14 days post-ADT. A heterogeneous increase in PSMA uptake was observed 3 to 4 weeks post-ADT. This phenomenon was definitively more evident in bone metastases: 13 (57%) of the metastasis, with a mean (range) SUVmax increase of 77% (8–238%). In one patient, already having bone metastases at baseline, three new bone metastases were observed post-ADT. Of lesions with reduced SUVmax, none disappeared. Conclusions Both in patient and region level, increase in PSMA uptake post-ADT is heterogenous and is seen most evidently in bone metastases. Preliminary results on a small cohort of patients suggest the clinical impact of ADT on improving the performance of 68Ga-PSMA PET in staging seems to be minor. However, the optimal imaging time point might be 3 to 4 weeks post-ADT. Since none of the metastases with decreasing SUVmax disappeared, it seems that short-term usage of ADT does not interfere with the interpretation of 68Ga-PSMA PET. Trial registration NCT03313726, registered 18 October 2017; EUDRA-CT, 2017-002345-29.

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Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging

Nuclear Medicine Communications ◽

10.1097/mnm.0000000000000290 ◽

2015 ◽

Vol 36 (6) ◽

pp. 582-587 ◽

Cited By ~ 83

Author(s):

Levent Kabasakal ◽

Emre Demirci ◽

Meltem Ocak ◽

Reşit Akyel ◽

Jamal Nematyazar ◽

...

Keyword(s):

Prostate Cancer ◽

Ct Imaging ◽

Psma Pet ◽

Pet Ct ◽

Pelvic Imaging

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11C-Choline PET/CT Predicts Prostate Cancer-Specific Survival in Patients with Biochemical Failure During Androgen-Deprivation Therapy

Journal of Nuclear Medicine ◽

10.2967/jnumed.113.123380 ◽

2014 ◽

Vol 55 (2) ◽

pp. 233-241 ◽

Cited By ~ 63

Author(s):

G. Giovacchini ◽

M. Picchio ◽

R. Garcia-Parra ◽

A. Briganti ◽

F. Abdollah ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Biochemical Failure ◽

Cancer Specific Survival ◽

Choline Pet ◽

Pet Ct

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Lymph Node Involvement in Treatment-Naïve Prostate Cancer Patients: Correlation of PSMA PET/CT Imaging and Roach Formula in 280 Men in Radiotherapeutic Management

Journal of Nuclear Medicine ◽

10.2967/jnumed.119.227637 ◽

2019 ◽

Vol 61 (1) ◽

pp. 46-50 ◽

Cited By ~ 6

Author(s):

Stefan A. Koerber ◽

Gerald Stach ◽

Clemens Kratochwil ◽

Matthias F. Haefner ◽

Henrik Rathke ◽

...

Keyword(s):

Prostate Cancer ◽

Lymph Node ◽

Cancer Patients ◽

Lymph Node Involvement ◽

Ct Imaging ◽

Psma Pet ◽

Pet Ct ◽

Treatment Naïve ◽

Node Involvement

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Detection Rate of 68Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy

Biomedicines ◽

10.3390/biomedicines8110511 ◽

2020 ◽

Vol 8 (11) ◽

pp. 511

Author(s):

Joachim Brumberg ◽

Melanie Beckl ◽

Alexander Dierks ◽

Andreas Schirbel ◽

Markus Krebs ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Detection Rate ◽

Androgen Deprivation ◽

Disease Stage ◽

Whole Body ◽

Recurrent Prostate Cancer ◽

Detection Rates ◽

Psma Ligand ◽

Pet Ct

Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of 68Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All 68Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7% vs. 72.6%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended.

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Prior PSMA PET-CT Imaging and Hounsfield Unit Impact on Tumor Yield and Success of Molecular Analyses from Bone Biopsies in Metastatic Prostate Cancer

Cancers ◽

10.3390/cancers12123756 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3756

Author(s):

Minke Smits ◽

Kamer Ekici ◽

Samhita Pamidimarri Naga ◽

Inge M. van Oort ◽

Michiel J. P. Sedelaar ◽

...

Keyword(s):

Prostate Cancer ◽

Molecular Characterization ◽

Metastatic Prostate Cancer ◽

Ct Imaging ◽

Ct Guidance ◽

Prediction Tool ◽

Psma Pet ◽

Pet Ct ◽

Bone Biopsies ◽

Tumor Yield

Developing and optimizing targeted therapies in metastatic castration-resistant prostate cancer (mCRPC) necessitates molecular characterization. Obtaining sufficient tumor material for molecular characterization has been challenging. We aimed to identify clinical and imaging variables of imaging-guided bone biopsies in metastatic prostate cancer patients that associate with tumor yield and success in obtaining molecular results, and to design a predictive model: Clinical and imaging data were collected retrospectively from patients with prostate cancer who underwent a bone biopsy for histological and molecular characterization. Clinical characteristics, imaging modalities and imaging variables, were associated with successful biopsy results. In our study, we included a total of 110 bone biopsies. Histological conformation was possible in 84 of all biopsies, of which, in 73 of the 84, successful molecular characterization was performed. Prior use of PSMA PET-CT resulted in higher success rates in histological and molecular successful biopsies compared to CT or MRI. Evaluation of spine biopsies showed more often successful results compared to other locations for both histological and molecular biopsies (p = 0.027 and p = 0.012, respectively). Low Hounsfield units (HUs) and deviation (Dev), taken at CT-guidance, were associated with histological successful biopsies (p = 0.025 and p = 0.023, respectively) and with molecular successful biopsies (p = 0.010 and p = 0.006, respectively). A prediction tool combining low HUs and low Dev resulted in significantly more successful biopsies, histological and molecular (p = 0.023 and p = 0.007, respectively). Based on these results, we concluded that site selection for metastatic tissue biopsies with prior PSMA PET-CT imaging improves the chance of a successful biopsy. Further optimization can be achieved at CT-guidance, by selection of low HU and low Dev lesions. A prediction tool is provided to increase the success rate of bone biopsies in mCRPC patients, which can easily be implemented in daily practice.

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Prostate-specific membrane antigen (PSMA) PET-CT imaging in the investigation and management of biochemical recurrence in prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.208 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 208-208 ◽

Cited By ~ 1

Author(s):

Fergus Keane ◽

Yasser Ged ◽

Megan Greally ◽

Michael A. Maher ◽

Kieran O'Malley ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Disease ◽

Biochemical Recurrence ◽

Systemic Disease ◽

Ct Imaging ◽

Prostate Specific Membrane Antigen ◽

Psma Pet ◽

Pet Ct ◽

Specific Membrane

208 Background: It is estimated that within ten years of primary treatment for prostate cancer up to 40% of patients post radical prostatectomy, and up to 50% of patients post radiotherapy will develop disease recurrence. While monitoring of PSA levels is informative of biochemical recurrence, it may precede radiologically detectable recurrence by months to years, and cannot differentiate local/regional recurrence from systemic disease. This represents a management dilemma for treating physicians. The incorporation of PET probes targeting prostate-specific membrane antigen (PSMA) for prostate cancer shows promise for improving the management of patients with prostate cancer, when used alongside existing imaging techniques, like CT, MRI and bone scans. Methods: Retrospective review of all patients referred from our institution for PSMA imaging was carried out. Baseline clinical features were determined and we analyzed impact of PSMA imaging on management outcomes and survival data. Results: 33 patients referred for 68Ga-PSMA-PET imaging were identified. Median age at diagnosis was 65 years (51 -75). The indication for referral in all patients was biochemical recurrence in the absence of radiological evidence of disease by CT imaging and bone scan. Median PSA at time of referral for PSMA scan was 7.3ug/L (1.4ug/L to 87.7ug/L). 100% of patients (n = 33) were upstaged following PSMA imaging, and 30% (n = 10) had more than one site of metastatic disease identified. Most common sites of metastasis were lymph node and bone. Median number of sites of metastatic disease identified by PSMA imaging was one. These results led to a change in management for 96% patients (n = 32). All patients at the time of this review are alive with a median follow up of 13 months, and median progression-free survival of 11 months. Conclusions: PSMA PET-CT directly led to an alteration in the treatment of the majority of patients in this study. This real world data reflects the growing role of PSMA imaging in influencing clinical decisions for prostate cancer patients with biochemical recurrence. Prospective data from randomized studies are awaited to further validate the role of PSMA PET-CT in this patient cohort.

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