High level PSMA expression is associated with early psa recurrence in surgically treated prostate cancer

Minner, Sarah; Wittmer, Corinna; Graefen, Markus; Salomon, Georg; Steuber, Thomas; Haese, Alexander; Huland, Hartwig; Bokemeyer, Carsten; Yekebas, Emre F.; Dierlamm, Judith; Balabanov, Stefan; Kilic, Ergin; Wilczak, Waldemar; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten

doi:10.1002/pros.21241

Cited by 248 publications

(198 citation statements)

References 37 publications

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“…For GS, significant correlations to SUVs were detected in the univariate linear regression model, which were not present in the multivariable regression analysis. A positive correlation between increasing GS and PSMA expression is in line with preclinical studies (25,26). Moreover, in a recently published large clinical retrospective study, 68 Ga-PSMA ligand PET/CT demonstrated a significantly higher detection efficacy in the setting of GS $ 8 in patients with relapsing PC (13), which was attributed to a higher PSMA expression in higher GS.…”

Section: Discussionsupporting

confidence: 72%

Detection Efficacy of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria

et al. 2017

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The aim of this retrospective study was to evaluate the detection rate of Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)] ( 68 Ga-PSMA ligand; PSMA is prostate-specific membrane antigen) PET/CT in patients with biochemical recurrent prostate cancer defined by Phoenix criteria after external-beam radiotherapy or brachytherapy as primary treatment. Methods: One hundred eighteen patients with a median prostate-specific antigen (PSA) of 6.4 ng/mL (range, 2.2-158.4 ng/mL; interquartile range, 4.2-10.2 ng/mL) were finally eligible for this retrospective analysis. Seventy-seven and 41 patients had been treated by external-beam radiotherapy or brachytherapy, respectively. Of the 118 patients, 45 were receiving androgen-deprivation therapy (ADT) within at least 6 mo before the PET/CT. The detection rates were stratified by PSA. The influence of primary Gleason score and ADT was assessed. Relationships between SUV and clinical as well as pathologic features in patients with positive findings were analyzed using univariate and multivariable linear regression models. Results: One hundred seven of 118 patients (90.7%) showed pathologic findings indicative for tumor recurrence in 68 Ga-PSMA ligand PET/CT. The detection rates were 81.8% (36/44), 95.3% (41/43), and 96.8% (30/31) for PSA of 2 to ,5, 5 to ,10, and $10 ng/mL, respectively (P 5 0.0377). 68 Ga-PSMA ligand PET/CT indicated local recurrence in 68 of 107 patients (63.5%), distant lesions in 64 of 107 patients (59.8%), and local recurrence as well as distant lesions in 25 of 107 patients (23.4%). The detection rate was significantly higher in patients with ADT (97.7%) versus without ADT (86.3%, P 5 0.0381), but independent from primary Gleason score $ 8 (92.0%) versus # 7 (90.2%, P 5 0.6346). SUV max and SUV mean were significantly associated with PSA and ADT (P 5 0.018 and 0.004 for SUV max , respectively; P 5 0.025 and 0.007 for SUV mean , respectively). Conclusion: 68 Ga-PSMA ligand PET/CT demonstrates high detection rates in patients with biochemical recurrence of prostate cancer after primary radiation therapy. The detection rate was positively associated to increasing PSA as well as concomitant ADT. 68 Ga-PSMA ligand PET/CT enables discrimination of local versus metastatic disease and thus might have a crucial impact on further clinical management. A major limitation of this study is the lack of histopathologic proof in most patients.

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Section: Discussionsupporting

confidence: 72%

Detection Efficacy of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria

et al. 2017

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“…Bound primary antibody was visualized using the DAKO EnVision Kit (Dako, Glostrup, Denmark). CRISP3 staining was evaluated according to the following scoring system as previously described: [21][22][23] The staining intensity (0, 1 þ , 2 þ , and 3 þ ) and the fraction of positive tumor cells were recorded for each tissue spot. A final score was built from these two parameters as follows: Negative: absence of CRISP3 staining; weak: intensity of 1 þ in r70% of tumor cells or staining intensity of 2 þ in r30% of tumor cells; moderate: intensity of 1 þ in 470% of tumor cells, or staining intensity of 2 þ in 430% but r70% of tumor cells or staining intensity of 3 þ r30% of tumor cells; strong: intensity of 2 þ in 470% of tumor cells or staining intensity of 3 þ in 430% of tumor cells.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence

et al. 2013

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The aim of this study was to determine whether cysteine-rich secretory protein 3 (CRISP3) expression is linked to clinically or molecularly relevant subgroups of prostate cancer. A tissue microarray representing samples from 410 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data were analyzed for CRISP3 expression by immunohistochemistry. CRISP3 expression was also compared with key genomic alterations of prostate cancer. CRISP3 staining was found as weak in 15%, moderate in 8.5%, and strong in 7.2% of prostate cancers, whereas no expression was detected in normal prostate. Strong CRISP3 expression was linked to advanced tumor stage, high Gleason score, and positive surgical margin status (Po0.0001 each). There was a marked accumulation of high CRISP3 expression in PTEN-deleted ERG-positive tumors (Po0.0001). A total of, 21.7% of ERG-positive and PTEN-deleted cancers had strong CRISP3 expression, but only 10.4% of ERG-positive cancers without PTEN deletion (Po0.0001). The rate of high CRISP3 expression was 2.5% in ERG-negative cancers (P ¼ 0.0001; vs ERG-positive cancers). Accordingly, CRISP3 overexpression was associated with early prostate-specific antigen recurrence in all tumors (P ¼ 0.0013) as well as in ERGnegative (P ¼ 0.004) and ERG-positive cancers (P ¼ 0.0318). CRISP3 expression did not retain prognostic significance in models also involving PTEN deletions. Strong CRISP3 expression is associated with unfavorable tumor phenotype and early recurrence in prostate cancers. The tight link of strong CRISP3 expression to the ERG fusion-positive prostate cancers with PTEN deletions provides further evidence for the existence of molecularly distinct subgroups of prostate cancers.

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“…Prostate speci ic membrane antigen (PSMA) is a membrane bound protein that is more avidly expressed in primary as well as in metastatic prostate cancer [4][5][6]. Extensive research is going on to develop PSMA ligands.…”

Section: Discussionmentioning

confidence: 99%

Near Complete Response to 177Lu-PSMA-DKFZ-617 Therapy in a Patient with Metastatic Castration Resistant Prostate Cancer

MP¹

2017

J Radiol Oncol

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High level PSMA expression is associated with early psa recurrence in surgically treated prostate cancer

Cited by 248 publications

References 37 publications

Detection Efficacy of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria

Detection Efficacy of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria

Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence

Near Complete Response to 177Lu-PSMA-DKFZ-617 Therapy in a Patient with Metastatic Castration Resistant Prostate Cancer

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High level PSMA expression is associated with early psa recurrence in surgically treated prostate cancer

Cited by 248 publications

References 37 publications

Detection Efficacy of Hybrid 68Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria

Detection Efficacy of Hybrid 68Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria

Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence

Near Complete Response to 177Lu-PSMA-DKFZ-617 Therapy in a Patient with Metastatic Castration Resistant Prostate Cancer

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Detection Efficacy of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria

Detection Efficacy of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria