scholarly journals Immunohistochemical Validation of PSMA Expression Measured by 68Ga-PSMA PET/CT in Primary Prostate Cancer

2017 ◽  
Vol 59 (2) ◽  
pp. 238-243 ◽  
Author(s):  
Nadine Woythal ◽  
Ruza Arsenic ◽  
Carsten Kempkensteffen ◽  
Kurt Miller ◽  
Jan-Carlo Janssen ◽  
...  
2020 ◽  
Vol 152 ◽  
pp. S104
Author(s):  
S. Spohn ◽  
C. Jaegle ◽  
A.S. Bettermann ◽  
S. Kiefer ◽  
C.A. Jilg ◽  
...  

2020 ◽  
Vol 19 ◽  
pp. e612
Author(s):  
C. Mengxia ◽  
Q. Xuefeng ◽  
F. Yao ◽  
Z. Qing ◽  
L. Danyan ◽  
...  

2019 ◽  
Vol 18 (1) ◽  
pp. e214
Author(s):  
X. Qiu ◽  
M. Chen ◽  
Z. Qing ◽  
J. Gao ◽  
C. Zhang ◽  
...  

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 295-295
Author(s):  
Carissa Chu ◽  
Mohammed Alshalalfa ◽  
Martin Sjöström ◽  
Shuang Zhao ◽  
Annika Herlemann ◽  
...  

295 Background: While 18F-fluciclovine PET/CT is approved in the US and recommended by the NCCN, prostate-specific membrane antigen (PSMA) PET/CT is more common in Europe/Australia and recommended by the EAU. Less is known about the biology of lesions detected by either modality. 18F-fluciclovine PET relies on radiotracer uptake by amino acid transporters LAT1-4 and ASCT1-2. PSMA PET is dependent on surface expression of PSMA. We compared relative expression of PSMA and fluciclovine transporter genes in radical prostatectomy (RP) samples to determine their distribution across subtypes and correlation with outcomes. Methods: Gene expression data of 19,102 RP samples were analyzed using the Affymetrix Human Exon 1.0 ST microarray. 1,135 patients had long term follow up. Associations between expression of PSMA and fluciclovine transporter genes (LAT1-4 and ASCT1-2) and pathologic variables, molecular subtypes, and clinical outcomes were conducted. Results: All fluciclovine transporter genes (LAT 1-4, ASCT1-2) were expressed at lower levels than PSMA (p <0.0001). PSMA expression was positively correlated with genomic risk score and pathologic Gleason score (p<0.0001), but LAT2-3 and ASCT2 were inversely correlated with genomic risk in primary tumors (p<0.0001) and less expressed in GS 9-10 tumors (p<0.0001). PSMA expression was associated with worse metastasis-free survival (MFS) (HR 1.45, p=0.001) and lymph node involvement (HR 2.14, p<0.0001). Expression of LAT2, LAT3, ASCT2 expression was associated with better MFS (HR 0.85, 0.63, 0.74, p<0.0001-0.04). After multivariable adjustment, PSMA expression remained independently prognostic of poorer MFS (HR 1.3, p=0.028). Luminal B subtype was notable for PSMA overexpression; Luminal A was enriched in ASCT2 and LAT2 (p<0.0001). PSMA expression did not correlate with ERG fusion prostate cancers, but LAT2, ASCT1, and ASCT2 were overexpressed in ERG fusion negative tumors (p<0.0001). Conclusions: PSMA expression is associated with more aggressive disease and poorer clinical outcomes than fluciclovine transporter genes in localized prostate cancer. Molecular subtypes of prostate cancer vary in PSMA and fluciclovine transporter gene expression.


2020 ◽  
Vol 203 ◽  
pp. e190-e191
Author(s):  
Mengxia Chen* ◽  
Xuefeng Qiu ◽  
Yao Fu ◽  
Qing Zhang ◽  
Feng Wang ◽  
...  

2019 ◽  
Vol 92 (1101) ◽  
pp. 20190286 ◽  
Author(s):  
Emine Acar ◽  
Asım Leblebici ◽  
Berat Ender Ellidokuz ◽  
Yasemin Başbınar ◽  
Gamze Çapa Kaya

Objective:Using CT texture analysis and machine learning methods, this study aims to distinguish the lesions imaged via 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT as metastatic and completely responded in patients with known bone metastasis and who were previously treated.Methods:We retrospectively reviewed the 68Ga-PSMA PET/CT images of 75 patients after treatment, who were previously diagnosed with prostate cancer and had known bone metastasis. A texture analysis was performed on the metastatic lesions showing PSMA expression and completely responded sclerotic lesions without PSMA expression through CT images. Textural features were compared in two groups. Thus, the distinction of metastasis/completely responded lesions and the most effective parameters in this issue were determined by using various methods [decision tree, discriminant analysis, support vector machine (SVM), k-nearest neighbor (KNN), ensemble classifier] in machine learning.Results:In 28 of the 35 texture analysis findings, there was a statistically significant difference between the two groups. The Weighted KNN method had the highest accuracy and area under the curve, has been chosen as the best model. The weighted KNN algorithm was succeeded to differentiate sclerotic lesion from metastasis or completely responded lesions with 0.76 area under the curve. GLZLM_SZHGE and histogram-based kurtosis were found to be the most important parameters in differentiating metastatic and completely responded sclerotic lesions.Conclusions:Metastatic lesions and completely responded sclerosis areas in CT images, as determined by 68Ga-PSMA PET, could be distinguished with good accuracy using texture analysis and machine learning (Weighted KNN algorithm) in prostate cancer.Advances in knowledge:Our findings suggest that, with the use of newly emerging software, CT imaging can contribute to identifying the metastatic lesions in prostate cancer.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 24-24
Author(s):  
Carissa Chu ◽  
Mohammed Alshalalfa ◽  
Martin Sjöström ◽  
Shuang Zhao ◽  
Annika Herlemann ◽  
...  

24 Background: 18F-fluciclovine (Axumin) PET/CT imaging is recommended by the NCCN in the setting of biochemical recurrence, while prostate-specific membrane antigen (PSMA) PET/CT is preferred by the EAU. The utility of these methods in the post-androgen deprivation therapy (ADT) setting however, is less defined. Our objective was to compare relative gene expression of the molecular targets of these imaging modalities— fluciclovine transporter genes (LAT1-4, ASCT1-2) and PSMA—in metastatic castrate resistant prostate cancer (mCRPC) and treatment-emergent small cell/neuroendocrine prostate cancer (t-SCNC). Methods: Genome-wide expression profiles of five mCRPC cohorts (Aggarwal, Grasso, Kumar, Beltran, Robinson, et al) were used to characterize relative expression of fluciclovine transporter (LAT1-4, ASC1-2) and PSMA (FOLH1) genes. 3 cohorts (Kumar, Beltran, Aggarwal) were enriched with t-SCNC tumors. The GSE35988 cohort included primary tumors and mCRPC. RNA expression profiling methods were consistent within cohorts. Results: 518 mCRPC specimens were included. In the GSE35988 cohort, PSMA expression was downregulated in mCRPC when compared to primary localized tumors (p=0.01). PSMA expression was further depressed in t-SCNC when compared with mCRPC (p<0.001). Of the fluciclovine transporter genes, LAT1 and LAT4 were overexpressed in mCRPC when compared to primary tumors, while ASC2 was less expressed (p<0.001). LAT1 was further overexpressed in t-SCNC when compared to mCRPC, while LAT2 was less expressed (p<0.001). PSMA expression was negatively correlated with LAT1 (p<0.001) but positively correlated with LAT2 (p=0.006). Other fluciclovine transporters were not correlated. Conclusions: Expression of PSMA and a subset of fluciclovine transporter genes are inversely correlated in mCRPC and t-SCNC. These findings suggest that fluciclovine-based imaging may play a role in castrate resistant states. Clinical comparison between PSMA- and fluciclovine-based imaging modalities in mCRPC and t-SCNC is warranted.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 193-193
Author(s):  
Ida Sonni ◽  
Ely Felker ◽  
Andrew Thomas Lenis ◽  
Anthony E Sisk ◽  
Shadfar Bahri ◽  
...  

193 Background: The local staging of prostate cancer relies on systematic or targeted biopsies and multiparametric magnetic resonance imaging (mpMRI). The role of prostate-specific membrane antigen (PSMA)-targeted PET in the evaluation of intraprostatic cancer foci and T-staging assessment is not well defined. The goal of this analysis was to compare the diagnostic performance of PSMA PET/CT, mpMRI and the combination of the two (PSMA PET/CT+mpMRI) in the detection, intra-prostatic localization and local extension of primary prostate cancer with histopathology as the gold standard.Methods: Patients with intermediate- or high-risk prostate cancer underwent a PSMA PET/CT scan and mpMRI prior to intended radical prostatectomy. Each imaging modality was interpreted by 3 blinded independent readers. A majority rule was applied (2:1). A standardized approach was used to assess presence, location and size of prostate cancer foci within the prostate. The analysis was conducted on a lesion- and segment-level. Whole mount pathology was interpreted by a Genito-Urinary pathologist using the same standardized method described above. Accuracy in determining the location, extra-capsular extension (ECE) and seminal vesicle invasion (SVI) of prostate cancer foci were assessed using receiver operating characteristic (ROC) analysis. A “raw-stringent” and “neighboring” approach were used to define imaging/pathology correlation for the detection of individual prostate cancer foci. Results: The final analysis included 74 patients. Detection rate was 75%, 79% and 82% using the “raw-stringent” approach, 86%, 83% and 87% using the “neighboring” approach for PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI, respectively. Differences in detection rates between PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI were not statistically significant. The two imaging modalities performed similarly (AUC = 0.70 vs 0.73, p = 0.09; AUC = 0.77 for the two together) in localizing prostate cancer. ΔAUC between PSMA PET/CT+mpMRI and the two imaging modalities alone was statistically significant (p < 0.001), but not between PSMA PET/CT and mpMRI (p = 0.093). mpMRI performed better than PSMA PET/CT in the T-staging assessment: ECE (AUC = 0.79 vs 0.59, p = 0.002) and SVI (AUC = 0.84 vs 0.63, p = 0.001). Conclusions: PSMA PET/CT and mpMRI have similar diagnostic accuracy in the detection and intra-prostatic localization of prostate cancer foci while mpMRI performs better in the assessment of ECE and SVI. The combination of the two imaging modalities improves performance of the two modalities alone, but this does not reach statistically significant levels on a lesion-level and might not justify changes in the current practices for local staging of prostate cancer.


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