Publications by authors named "Martin Bögemann"

46 Publications

[Apalutamide in patients with high-risk M0CRPC: data from the pivotal SPARTAN study and initial experience from a compassionate use program].

Aktuelle Urol 2021 Feb 23. Epub 2021 Feb 23.

Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie, Münster.

Non-metastatic castration-resistant prostate carcinoma (M0CRPC) is associated with an increased risk of progression and mortality, especially if the prostate-specific antigen doubling time is short (PSADT ≤ 10 months). The risk of progression and mortality increases even further if the disease progresses to the metastatic stage (mCRPC). The androgen receptor inhibitors apalutamide, darolutamide and enzalutamide, each in combination with androgen deprivation therapy (ADT), are available for the treatment of patients with high-risk M0CRPC.Data from the pivotal SPARTAN study showed that apalutamide + ADT delayed metastasis-free survival (MFS) and thus also the development of mCRPC in these patients. Prior to the approval of apalutamide in the European Union, the active substance was available in Germany as part of an international compassionate use program. A total of 109 patients from 50 centres participated in Germany: 45 patients were treated for more than 3 months and 13 patients for more than 6 months. The compassionate use program continues in some countries; 556 patients have been enrolled worldwide.In our experience, this real-world population showed a good PSA response, which was also shown for this exploratory endpoint in the SPARTAN study. We were also unable to identify any significant differences from the pivotal trial with regards to the tolerability profile.Apalutamide in combination with ADT was also effective in this real-world population and led to a rapid decrease in PSA. The tolerability profile did not differ from that in the SPARTAN trial.
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http://dx.doi.org/10.1055/a-1356-5055DOI Listing
February 2021

Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors.

Prostate Cancer Prostatic Dis 2021 Feb 8. Epub 2021 Feb 8.

Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA.

Background: Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit-risk profile of potential treatments is required.

Methods: In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function.

Results And Conclusions: While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit-risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.
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http://dx.doi.org/10.1038/s41391-020-00310-3DOI Listing
February 2021

Prostate-specific Membrane Antigen-based Imaging of Castration-resistant Prostate Cancer.

Eur Urol Focus 2021 Mar 20;7(2):279-287. Epub 2021 Jan 20.

West German Cancer Center; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.

Context: Positron emission tomography (PET) targeting prostate-specific membrane antigen (PSMA) has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC). There is now growing evidence regarding the value of PSMA-PET in patients with advanced PC.

Objective: To review the value of PSMA-PET/computed tomography (CT) in the context of castration-resistant PC (CRPC).

Evidence Acquisition: A search of the PubMed database using the terms "PSMA PET castration resistant prostate cancer" (years 2011-2020) was performed. Reviews, case reports/series, non-English articles, preclinical studies, access-restricted studies, and studies on PSMA radioligand therapy without further analysis of PSMA-PET parameters were subsequently excluded.

Evidence Synthesis: Compared to conventional imaging, PSMA-PET better identifies the true extent of CRPC, especially nonmetastatic CRPC. The clinical benefit of this stage migration is still unclear and needs to be evaluated in further studies. High accuracy of PSMA-PET holds promise for better, PET-guided metastasis-directed treatment in patients with oligometastatic CRPC. PSMA-PET is an essential eligibility criterion for [Lu]-PSMA theranostic applications. Preliminary evidence indicates the value of PSMA-PET for the assessment of treatment responses.

Conclusions: Among other applications, PSMA-PET offers more precise staging for nonmetastatic CRPC. In particular, target localization for metastasis-directed therapy and target expression assessment for PSMA radioligand therapy also hold promise. Potential translation of this diagnostic tool into an oncologic benefit needs to be defined in future trials.

Patient Summary: This review describes how prostate-specific membrane antigen positron emission tomography (PSMA-PET), a new sensitive imaging tool for prostate cancer, might help to guide clinicians in making treatment decisions for advanced prostate cancer.
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http://dx.doi.org/10.1016/j.euf.2021.01.002DOI Listing
March 2021

Do fasting or high caloric drinks affect the physiological uptake of fluorine-18 prostate-specific membrane antigen-1007 in liver and bowel?

World J Nucl Med 2020 Jul-Sep;19(3):220-223. Epub 2019 Nov 7.

Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.

Recently introduced fluorine-18 prostate-specific membrane antigen-1007 (F-PSMA-1007) for imaging prostate cancer has an intense physiologic liver uptake and biliary excretion. The aim of the present study was to evaluate the effect of different dietary conditions on this physiological uptake. Forty consecutive prostate cancer patients were scanned with F-PSMA-1007 positron emission tomography/computed tomography at different dietary conditions. In addition to a blinded read scoring, tracer uptake intensities (standardized uptake values [SUVs]) were measured in the liver and small bowel. There was no significant difference in liver and small-bowel uptake between different patient groups. Wilcoxon signed-rank tests revealed no significant difference of the median mean SUV of the liver or maximum SUV of the horizontal part of the duodenum between different dietary conditions groups. A dietary preparation of patients by fasting or the attempt to clear liver activity by high caloric drinks does not have a significant effect on tracer uptake in the liver or in the small bowel.
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http://dx.doi.org/10.4103/wjnm.WJNM_6_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745857PMC
November 2019

Using Data from a Sickness Fund Claims Database to Assess the Treatment Patterns and Healthcare Resource Utilization among Patients with Metastatic Renal Cell Carcinoma in Germany.

Urol Int 2020 29;104(11-12):982-993. Epub 2020 Sep 29.

Kantar GmbH, Munich, Germany.

Objectives: To characterize real-world prescribing patterns and their clinical and healthcare resource utilization (HRU) implications in patients with metastatic renal cell carcinoma (mRCC) treated in Germany.

Methods: Eligible individuals were enrolled in the "Bundesverband der Betriebskrankenkassen" claims database and received targeted mRCC therapy between 1 January 2008 and 31 December 2016. Prescribing patterns and HRU were characterized by treatment line and summarized by descriptive statistics. Proxy progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier curves.

Results: 536 patients receiving mRCC treatment were included. The median treatment duration was 4.2 months (interquartile range [IQR]: 1.7-9.3) for first-line therapy and 3.8 months (IQR: 1.7-9.1) for second-line therapy. Median PFS and OS estimates were similar for the first- and second-line treatments: PFS, 7.4 versus 7.2 months; OS, 14.9 versus 13.6 months. Mean HRU costs were higher for patients receiving first-line therapy (€7,253.2) compared with those receiving second-line therapy (€6,242.9). Exploratory stratification of outcomes by centre expertise suggested a possible trend towards improved OS in the 10 most experienced centres versus all -others: first-line, 18.4 versus 13.2 months; second-line, 16.4 versus 12.4 months.

Conclusions: In routine care, German clinicians make rational prescribing decisions; possible variations in outcomes between centres warrant further investigation.
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http://dx.doi.org/10.1159/000509973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845442PMC
September 2020

Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial.

Lancet Oncol 2020 12 21;21(12):1574-1588. Epub 2020 Sep 21.

Beth Israel Deaconess Medical Center and PSMAR-IMIM Research Lab, Harvard Medical School, Boston, MA, USA.

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma.

Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice-web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24.

Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9-43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4-17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4-15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71-1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1-18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9-14·0) in the chemotherapy group (0·85, 95% CI 0·72-1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (<1%) patient in the chemotherapy group (acute kidney injury).

Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted.

Funding: AstraZeneca.
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http://dx.doi.org/10.1016/S1470-2045(20)30541-6DOI Listing
December 2020

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving Lu-PSMA-617 Radioligand Therapy.

Theranostics 2020 18;10(17):7645-7655. Epub 2020 Jun 18.

Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.

Lu-177-PSMA-617 radioligand therapy (RLT) is currently under approval for treatment of metastatic castration resistant prostate cancer (mCRPC) patients with late stage disease. However, previous studies demonstrated both heterogeneity of prostate specific membrane antigen (PSMA) expression, as well as response to PSMA treatment among mCRPC patients. Thus, there is an unmet need for identifying predictive parametres prior or under PSMA-RLT treatment. We therefore aimed to correlate several clinical and molecular parameters with response to PSMA treatment in a cohort of mCRPC patients undergoing PSMA RLT followed by a detailed analysis of promising candidates. Nineteen patients, median age 68.8 years (range: 56.9 - 83.3) with mCRPC were included in this study. We performed baseline analysis of clinical parameters based on PSMA PET/CT, (metabolic tumor volume (MTV), total tumor volume (TTV)), serum PSA, ALP, LDH and gene expression analysis of circulating tumor cells (expression of AR full length (AR-FL), AR splice variant 7 (AR-V7), PSA and PSMA) as well as common markers for neuroendocrine differentiation (NED). Patients presented with bone, lymph node, and visceral metastases (89%, 68%, and 21%, respectively). All patients were pretreated with docetaxel, either abiraterone or enzalutamide, or both. Biochemical response in terms of PSA decline ≥50 or ≥30% was observed in 42% and 63%, respectively. There were significant correlations between PSA and PSMA mRNA expression, as well as tumor volumes (both MTV and TTV), AR-FL and AR-V7 mRNA expression. However, there was no correlation with response to PSMA treatment. Furthermore, none of these parameters was significantly correlated with baseline serum PSA values. Common NED markers were shown to be specifically high expressed and revealed impact on OS independent from AR-V7 gene expression. We demonstrate that AR-FL and its splice variant AR-V7 might serve as prognostic biomarkers displaying high tumor burden in mCRPC patient prior to PSMA-RLT. Contrary, PSMA, which has been discussed as a biomarker for PSMA targeted treatment, does not display strong prognostic ability - at least on the mRNA level. Surprisingly, none of these parameters correlates to response to PSMA treatment. In contrast, commom NED markers such as SYP and ENO2 as well as FOXA1 expression level seem to predict OS, but not PFS, more reliably. We admit that a limitation of our study is the focus on mRNA expression of potential biomarkers only. Further investigations analyzing the potential role of protein expression of these markers are therefore warranted.
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http://dx.doi.org/10.7150/thno.44556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359074PMC
June 2020

Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial).

Eur J Nucl Med Mol Imaging 2021 Jan 8;48(1):113-122. Epub 2020 May 8.

Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.

Introduction: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with Lu-PSMA-617.

Materials And Methods: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated.

Results: The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS.

Conclusion: In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0-1 is associated with a longer OS.
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http://dx.doi.org/10.1007/s00259-020-04797-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835179PMC
January 2021

[Early- vs. late-onset treatment using abiraterone acetate plus prednisone in chemo-naïve, asymptomatic or mildly symptomatic patients with metastatic CRPC after androgen deprivation therapy].

Aktuelle Urol 2020 Dec 8;51(6):562-571. Epub 2020 Apr 8.

Universitätsklinikum Münster, Urologie, Münster.

Background:  Abiraterone acetate (AA) is a prodrug of abiraterone, which is an irreversible inhibitor of 17α-hydroxylase/C17, 20-lyase. Since 2011, abiraterone acetate has been available in combination with prednisone/prednisolone (AA + P) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) after pre-treatment with docetaxel, and since 2012 for the treatment of chemotherapy-naïve asymptomatic or mildly symptomatic mCRPC patients. A revision of the guidelines of the European Association of Urology in 2014 redefining castration resistance gave rise to the question of when the treatment of mCRPC with abiraterone acetate plus prednisone should be initiated after prior hormone treatment and how successful it would be. This led us to observe an early-onset AA + P therapy cohort (EC) and a late-onset therapy cohort (LC) of patients.

Patients And Methods:  We designed a combined retrospective and prospective, multicentre, non-interventional two-cohort study to obtain data on the effectiveness and safety of an early-onset AA + P therapy in mCRPC patients in the clinical routine compared to a late therapy onset. The EC comprised patients who received AA + P immediately after castration resistance without a prior first-generation antiandrogen such as bicalutamide or flutamide. The LC included patients who, after castration resistance had occurred, started treatment with AA + P only after unsuccessful treatment with a first-generation antiandrogen. Patients with mCRPC who received AA + P therapy according to the physician's routine clinical practice decision were considered. The patients were consecutively included in the study on the basis of their medical records, with the treatment decision having been made independently of and before patient enrolment. Patients were documented or followed from the beginning of AA + P therapy until the start of a carcinoma-specific systemic follow-up therapy (retrospectively if before and prospectively if after start of data collection). Effectiveness analyses were done for all patients with at least two AA + P administrations and safety analyses for all treated patients.

Results:  Of the 159 patients included, 44 received early therapy and 105 received later therapy with AA + P. 10 patients could not be clearly assigned and were summarised in a third cohort (missed early-onset therapy assignment; MEC). 56/159 patients (35.2 %) were still alive at study start and 103/159 patients (64.8 %) had already deceased (31/44 [70.5 %] in EC, 64/105 [61.0 %] in LC, and 8/10 [80.0 %] in MEC). 24/159 patients (15.1 %) were documented both retrospectively and prospectively. The median duration of AA + P treatment was 11.3 months for EC, 12.0 months for LC, and 8.3 months for MEC patients. The median time to next systemic cancer therapy or death was 12.3 months for EC and 12.8 months for LC patients (p = 0.2820). The median time to the next systemic cancer therapy alone (i. e. without the event 'death') was 22.7 months for EC and 23.3 months for LC patients (p = 0.5995). Median overall survival (OS) was 22.3 months for EC and 39.2 months for LC patients (p = 0.0232). The incidence of serious adverse events (SAEs) was low. SAEs occurred in 3/44 EC (6.8 %), 4/105 LC (3.8 %), and 1/10 MEC patients (10.0 %). One SAE in EC and one in LC resulted in death.

Conclusions:  In contrast to the new definition of castration resistance, AA + P was still more frequently used in daily clinical practice during the study observation period in patients treated with antiandrogens of the first generation after occurrence of castration resistance. Nevertheless, AA + P therapy appears to be effective and well tolerated during clinical routine in mCRPC patients. A comparison of the study results with earlier 'real-world' studies, however, has to take limiting factors into account. The observed difference in median overall survival might be explained by the imbalance of baseline characteristics between both cohorts with regard to number of patients, patients already deceased at start of documentation, patients with visceral metastases and patients with opioids at start of AA + P. For these reasons, patients in the EC initially might have had a poorer prognosis. A prospective randomised and controlled clinical trial would therefore be necessary to assess a possible difference in overall survival and response of the AA + P treatment with respect to therapy onset.
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http://dx.doi.org/10.1055/a-1121-7593DOI Listing
December 2020

Radioligand therapy using [Lu]Lu-PSMA-617 in mCRPC: a pre-VISION single-center analysis.

Eur J Nucl Med Mol Imaging 2020 08 16;47(9):2106-2112. Epub 2020 Feb 16.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany.

Background: Radioligand therapy with [Lu]Lu-PSMA-617 is efficacious for the treatment of patients with metastasized castration-resistant prostate cancer (mCRPC). Various studies have evaluated the efficacy and safety of [Lu]Lu-PSMA-617 using a dose of 6.0 GBq and an 8-week therapy interval. However, the first prospective phase III trial (VISION) plans to use an elevated cumulative dose by applying 7.5 GBq in a 6-week interval. The aim of the present study was to compare safety and efficacy of the two aforementioned [Lu]Lu-PSMA-617 therapy regimes (7.5 GBq every 6 weeks vs. 6.0 GBq every 8 weeks).

Methods: A total number of 78 consecutive patients with mCRPC and a history of first-line chemotherapy were included in this retrospective analysis. The outcome of patients treated with 6.0 GBq [Lu]Lu-PSMA-617 per cycle (n = 37) were compared with those treated with 7.5 GBq (n = 41) per cycle. The median therapy intervals were 8.4 weeks (6.0 GBq group) vs. 6.5 (7.5 GBq group). PSA response, PSA progression-free survival (PSA-PFS), overall survival, and adverse events were evaluated and compared between both groups. Chi-squared test, Kaplan Meier estimates, Cox regression, and log-rank test were used. The highest decline from pretherapeutic PSA levels was measured as percentage (best PSA response) and compared between groups by Wilcoxon test.

Results: There was no significant difference comparing the rate of > 50% PSA decline or best PSA response between the 6.0 GBq and 7.5 GBq group (35% vs. 54%, p = 0.065; and - 40.2% vs. - 57.8%, p = 0.329). The median estimated survival and PSA-PFS did not significantly differ between the 6.0 GBq and 7.5 GBq groups as well (11.3 vs. 12.7 months, p = 0.384; and 9.5 vs. 12.3 months, p = 0.258). There was no significant difference regarding the change of kidney, liver, and blood cell parameters under therapy between the treatment groups.

Conclusion: Higher cumulated doses of [Lu]Lu-PSMA-617 were well tolerated and caused no significantly increased rate of adverse reactions. Moreover, 7.5 GBq of [Lu]Lu-PSMA-617 every 6 weeks causes slightly higher, though not statistically significant, response rates and seems therefore to be the preferable treatment regime. However, future studies are needed to elucidate the dose-related efficacy of [Lu]Lu-PSMA-617 as a way to personalized medicine.
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http://dx.doi.org/10.1007/s00259-020-04703-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338828PMC
August 2020

The Association of the Long Prostate Cancer Expressed PDE4D Transcripts to Poor Patient Outcome Depends on the Tumour's TMPRSS2-ERG Fusion Status.

Prostate Cancer 2019 2;2019:8107807. Epub 2019 Jun 2.

Philips Research Europe, 5656AE Eindhoven, Netherlands.

Objectives: To investigate the added value of assessing transcripts for the long cAMP phosphodiesterase-4D (PDE4D) isoforms, PDE4D5 and PDE4D9, regarding the prognostic power of the 'CAPRA & PDE4D7' combination risk model to predict longitudinal postsurgical biological outcomes in prostate cancer.

Patients And Methods: RNA was extracted from both biopsy punches of resected tumours (606 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). RT-qPCR was performed in order to determine PDE4D5, PDE4D7, and PDE4D9 transcript scores in both study cohorts. By RNA sequencing, we determined the TMPRSS2-ERG fusion status of each tumour sample in the RP cohort. Kaplan-Meier survival analyses were then applied to correlate the PDE4D5, PDE4D7 and PDE4D9 scores with postsurgical patient outcomes. Logistic regression was then used to combine the clinical CAPRA score with PDE4D5, PDE4D7, and PDE4D9 scores in order to build a 'CAPRA & PDE4D5/7/9' regression model. ROC and decision curve analysis was used to estimate the net benefit of the 'CAPRA & PDE4D5/7/9' risk model.

Results: Kaplan-Meier survival analysis, on the RP cohort, revealed a significant association of the PDE4D7 score with postsurgical biochemical recurrence (BCR) in the presence of the TMPRSS2-ERG gene rearrangement (logrank p<0.0001), compared to the absence of this gene fusion event (logrank p=0.08). In contrast, the PDE4D5 score was only significantly associated with BCR in TMPRSS2-ERG fusion negative tumours (logrank p<0.0001 vs. logrank p=0.4 for TMPRSS2-ERG+ tumours). This was similar for the PDE4D9 score although less pronounced compared to that of the PDE4D5 score (TMPRSS2ERG- logrank p<0.0001 vs. TMPRSS2ERG+ logrank p<0.005). In order to predict BCR after primary treatment, we undertook ROC analysis of the logistic regression combination model of the CAPRA score with the PDE4D5, PDE4D7, and PDE4D9 scores. For the DB cohort, this demonstrated significant differences in the AUC between the CAPRA and the PDE4D5/7/9 regression model vs. the CAPRA and PDE4D7 risk model (AUC 0.87 vs. 0.82; p=0.049) vs. the CAPRA score alone (AUC 0.87 vs. 0.77; p=0.005). The CAPRA and PDE4D5/7/9 risk model stratified 19.2% patients of the DB cohort to either 'no risk of biochemical relapse' (NPV 100%) or the 'start of any secondary treatment (NPV 100%)', over a follow-up period of up to 15 years. Decision curve analysis presented a clear, net benefit for the use of the novel CAPRA & PDE4D5/7/9 risk model compared to the clinical CAPRA score alone or the CAPRA and PDE4D7 model across all decision thresholds.

Conclusion: Association of the long PDE4D5, PDE4D7, and PDE4D9 transcript scores to prostate cancer patient outcome, after primary intervention, varies in opposite directions depending on the TMPRSS2-ERG genomic fusion background of the tumour. Adding transcript scores for the long PDE4D isoforms, PDE4D5 and PDE4D9, to our previously presented combination risk model of the combined 'CAPRA & PDE4D7' score, in order to generate the CAPRA and PDE4D5/7/9 score, significantly improves the prognostic power of the model in predicting postsurgical biological outcomes in prostate cancer patients.
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http://dx.doi.org/10.1155/2019/8107807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582815PMC
June 2019

SPARTAN: Gezielte Analyse der Resistenzen.

Authors:
Martin Bögemann

Oncol Res Treat 2019 8;42 Suppl 2. Epub 2019 Apr 8.

Beim metastasierten kastrationsresistenten Prostatakarzinom (mCRPC) erfolgt heute eine Sequenztherapie. Daher müssen sich neue Wirkstoffe, die früher - im nicht-metastasierten kastrationsresistenten Stadium (M0CRPC) mit hohem Metastasierungsrisiko - eingesetzt werden, ebenfalls in diese Sequenz einfügen.
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http://dx.doi.org/10.1159/000496366DOI Listing
April 2019

A Self-Fulfilling Prophecy: Comparing Lu-PSMA Radioligand Therapy in Taxane-Naïve Versus Posttaxane Metastasized Prostate Cancer Patients?

J Nucl Med 2019 10 29;60(10):1494. Epub 2019 Mar 29.

University Hospital Muenster Albert-Schweitzer-Campus 1 48149 Münster, Germany E-mail:

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http://dx.doi.org/10.2967/jnumed.119.228742DOI Listing
October 2019

Detection of Local Relapse of Prostate Cancer With 18F-PSMA-1007.

Clin Nucl Med 2019 Jun;44(6):e394-e395

From the Departments of Nuclear Medicine.

Prostate-specific membrane antigen (PSMA)-targeted PET/CT has become a fundamental tool in the management of patients with prostate cancer, especially to rule out local recurrence after surgery or radiation. However, the assessment of the prostatic fossa is difficult due to the renal excretion of PSMA-targeted radionuclides. PET/CT studies using Ga-PSMA-11 PET/CT and F-PSMA-1007 of a 61-year-old man after radical prostatectomy are presented. This case illustrates that F-PSMA-1007 is an ideal radionuclide for the detection of local recurrence of prostate cancer and is superior to Ga-PSMA-11, especially in case of pelvic lesions.
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http://dx.doi.org/10.1097/RLU.0000000000002543DOI Listing
June 2019

SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11).

Eur J Cancer 2019 01 7;107:37-45. Epub 2018 Dec 7.

Dept. of Urology, Rechts der Isar Medical Center, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany; AUO Study Group, Germany. Electronic address:

Purpose: This trial compared the sequential therapy with the multikinase inhibitor sorafenib (So) followed by pazopanib (Pa) or vice versa in advanced/metastatic renal cell carcinoma (mRCC) patients.

Methods: This multicenter, randomized phase 3 study assessed the sequential use of So-Pa versus Pa-So in patients with mRCC without prior systemic therapy. Pts were randomized to So 2 × 400 mg/day followed by Pa 1 × 800 mg/day in case of progression or intolerable toxicity or vice versa. Primary endpoint was total PFS (tPFS), defined as time from randomization to progression, or death during second-line therapy. Key secondary endpoints included overall survival (OS), first-line PFS, disease control rate (DCR) and safety.

Results: A total of 377 pts were randomized (So-Pa, n = 189; Pa-So, n = 188). Recruitment of a total 544 pts was calculated, but actual accrual rate turned out to be lower than expected. The primary endpoint median tPFS was 8.6 mo (95% CI 7.7-10.2) for So-Pa and 12.9 mo (95% CI 10.8-15.2) for Pa-So with a hazard ratio (HR) of 1.36 (upper limit of one-sided 95% CI 1.68), which exceeded a predefined HR <1.225 as a one-sided 95% confidence interval. Non-inferiority of So-Pa regarding tPFS was not met. Secondary endpoints displayed marked statistical differences in favor of Pa-So in first-line PFS and DCR but not for OS and 2nd-line PFS. Side effect profiles were consistent with known toxicities of the respective multikinase-inhibitor including diarrhea, fatigue, hand-foot skin reaction and hypertension.

Conclusions: Non-inferiority of the primary endpoint tPFS could not be demonstrated for So-Pa. The results for first-line PFS and DCR favored the Pa-So sequence.

Trial Registration: NCT01613846, www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.ejca.2018.11.001DOI Listing
January 2019

The Prognostic PDE4D7 Score in a Diagnostic Biopsy Prostate Cancer Patient Cohort with Longitudinal Biological Outcomes.

Prostate Cancer 2018 26;2018:5821616. Epub 2018 Jul 26.

Philips Research Europe, High Tech Campus 34, 5656AE Eindhoven, Netherlands.

To further validate the prognostic power of the biomarker PDE4D7, we investigated the correlation of PDE4D7 scores adjusted for presurgical clinical variables with longitudinal postsurgical biological outcomes. RNA was extracted from biopsy punches of resected tumors (550 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). Cox regression and survival were applied to correlate PDE4D7 scores with patient outcomes. Logistic regression was used to combine the clinical CAPRA score with PDE4D7. In univariate analysis, the PDE4D7 score was significantly associated with PSA recurrence after prostatectomy in both studied patient cohorts' analysis (HR 0.53; 95% CI 0.41-0.67; p<1.0E-04 and HR 0.47; 95% CI 0.33-0.65; p<1.0E-04, respectively). After adjustment for the presurgical clinical variables preoperative PSA, PSA density, biopsy Gleason, clinical stage, percentage tumor in the biopsy (data only available for RP cohort), and percentage of positive biopsies, the HR was 0.49 (95% CI 0.38-0.64; p<1.0E-04) and 0.43 (95% CI 0.29-0.63; p<1.0E-04), respectively. The addition of the PDE4D7 to the clinical CAPRA score increased the AUC by 5% over the CAPRA score alone (0.82 versus 0.77; p=0.004). This combination model stratified 14.6% patients of the DB cohort to no risk of biochemical relapse (NPV 100%) over a follow-up period of up to 15 years. The PDE4D7 score provides independent risk information for pretreatment risk stratification. Combining CAPRA with PDE4D7 scores significantly improved the clinical risk stratification before surgery.
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http://dx.doi.org/10.1155/2018/5821616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083737PMC
July 2018

Long-term Survival and Excellent Response to Repeated 177Lu-Prostate-Specific Membrane Antigen 617 Radioligand Therapy in a Patient With Advanced Metastatic Castration-Resistant Prostate Cancer.

Clin Nucl Med 2018 Oct;43(10):755-756

From the Departments of Nuclear Medicine and.

Radiolabeled ligands targeting prostate-specific membrane antigen (PSMA) are currently being established. Prostate-specific membrane antigen radioligand therapy with Lu-PSMA-617 is a promising treatment in metastasized castration-resistant prostate cancer with high efficacy and safety and seems to prolong progression-free survival and overall survival. We present Ga-PSMA PET/CT images during and after 2 therapy courses, including each 4 cycles of Lu-PSMA-617, and prostate-specific antigen-level history of a 77-year-old heavily pretreated patient with metastasized castration-resistant prostate cancer.
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http://dx.doi.org/10.1097/RLU.0000000000002212DOI Listing
October 2018

Diagnostic performance of F-PSMA-1007 PET/CT in patients with biochemical recurrent prostate cancer.

Eur J Nucl Med Mol Imaging 2018 11 20;45(12):2055-2061. Epub 2018 Jul 20.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Purpose: The introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced F-PSMA-1007 in patients with recurrent PCa.

Methods: This retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75 ± 7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338 ± 44.31 MBq F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level.

Results: Of the 100 patients, 95 (95%) showed at least one pathological finding on F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04-41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51-1.0, 1.1-2.0 and > 2.0 ng/ml, respectively. The median GS was 7 (range 5-10). The majority of patients (70) with a GS available had a score in the range 7-9. The rate of pathological scans in these patients was 93% (65/70). The median SUV values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51-1.0, 1.1-2.0 and >2.0 ng/ml, respectively. The median SUV in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups.

Conclusion: F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients.
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http://dx.doi.org/10.1007/s00259-018-4089-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182394PMC
November 2018

F-PSMA-1007 PET/CT at 60 and 120 minutes in patients with prostate cancer: biodistribution, tumour detection and activity kinetics.

Eur J Nucl Med Mol Imaging 2018 07 14;45(8):1329-1334. Epub 2018 Mar 14.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Purpose: PSMA-targeted PET in patients with prostate cancer (PCa) has a significant impact on treatment decisions. By far the most frequently used PSMA ligand is Ga-labelled PSMA-11. However, due to the availability of larger amounts of activity, F-labelled PSMA ligands are of major interest. The aim of the present study was to evaluate the biodistribution and performance of the novel F-labelled ligand PSMA-1007 at two different time points.

Methods: This retrospective analysis included 40 consecutive patients (mean age 68.7 ± 8.1 years) referred for PSMA PET/CT. F-PSMA-1007 PET/CT was performed for localization of biochemical relapse, primary staging or therapy follow-up. Circular regions of interest were placed on representative slices of the liver, spleen, kidney, abdominal aortic blood pool, bone marrow (fourth lumbar vertebral body), urinary bladder and gluteus muscle at 60 and 120 min after injection. In malignant lesions the maximum standardized uptake (SUV) was measured within volumes of interest at both time points. All SUVs at 60 min were compared with those at 120 min after injection.

Results: The activity in the blood pool, urinary bladder and gluteus muscle was very low and decreased significantly over time (P < 0.001). Uptake in the liver, spleen and kidney showed a significant increase over time and uptake in the bone marrow remained stable. Overall, 135 PCa lesions were detected at 60 min and 136 lesions at 120 min after injection. The median SUV increased significantly (P < 0.001) from 10.98 to 15.51 between 60 and 120 min.

Conclusion: PCa lesions show a significant increase in F-PSMA-1007 uptake at 120 min compared with 60 min after injection. In addition, accumulation of the tracer in the urinary bladder was very low leading to improved contrast of adjacent PCa lesions. Increasing accumulation in the liver may limit the sensitivity of the tracer in detecting liver metastases.
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http://dx.doi.org/10.1007/s00259-018-3989-0DOI Listing
July 2018

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid.

Oncotarget 2018 Feb 4;9(11):9867-9874. Epub 2018 Jan 4.

Gerhard Domagk Institute of Pathology, University of Münster, Münster, Germany.

Aim: PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions.

Methods: Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining.

Results: PSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors ( = 0.021). However, one case with a strong expression in follicular adenoma was identified.

Conclusions: We conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer.
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http://dx.doi.org/10.18632/oncotarget.23984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839407PMC
February 2018

Advantage of F-PSMA-1007 over Ga-PSMA-11 PET imaging for differentiation of local recurrence vs. urinary tracer excretion.

Eur J Nucl Med Mol Imaging 2018 06 14;45(6):1076-1077. Epub 2018 Feb 14.

Department of Urology, University Hospital Muenster, 48149, Münster, Germany.

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http://dx.doi.org/10.1007/s00259-018-3952-0DOI Listing
June 2018

Performance comparison of two androgen receptor splice variant 7 (AR-V7) detection methods.

BJU Int 2018 08 14;122(2):219-226. Epub 2018 Feb 14.

Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.

Objectives: To compare the performance of two established androgen receptor splice variant 7 (AR-V7) mRNA detection systems, as paradoxical responses to next-generation androgen-deprivation therapy in AR-V7 mRNA-positive circulating tumour cells (CTC) of patients with castration-resistant prostate cancer (CRPC) could be related to false-positive classification using detection systems with different sensitivities.

Materials And Methods: We compared the performance of two established mRNA-based AR-V7 detection technologies using either SYBR Green or TaqMan chemistries. We assessed in vitro performance using eight genitourinary cancer cell lines and serial dilutions in three AR-V7-positive prostate cancer cell lines, as well as in 32 blood samples from patients with CRPC.

Results: Both assays performed identically in the cell lines and serial dilutions showed identical diagnostic thresholds. Performance comparison in 32 clinical patient samples showed perfect concordance between the assays. In particular, both assays determined AR-V7 mRNA-positive CTCs in three patients with unexpected responses to next-generation anti-androgen therapy. Thus, technical differences between the assays can be excluded as the underlying reason for the unexpected responses to next-generation anti-androgen therapy in a subset of AR-V7 patients.

Conclusions: Irrespective of the method used, patients with AR-V7 mRNA-positive CRPC should not be systematically precluded from an otherwise safe treatment option.
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http://dx.doi.org/10.1111/bju.14146DOI Listing
August 2018

Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives.

Eur J Nucl Med Mol Imaging 2018 05 15;45(5):860-877. Epub 2018 Jan 15.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Background: Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression.

Conclusions: The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.
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http://dx.doi.org/10.1007/s00259-017-3922-yDOI Listing
May 2018

Comparison of isolation platforms for detection of circulating renal cell carcinoma cells.

Oncotarget 2017 Oct 23;8(50):87710-87717. Epub 2017 Sep 23.

Clinic for Urology, University Hospital Muenster, Muenster, Germany.

Background: Analysis of circulating tumor cells (CTCs) has progressed in several tumor entities. However, little is known about CTCs in clear cell renal cell carcinoma (ccRCC) patients. Aim of our studies was to build a stable fundament for isolation of CTCs in ccRCC.

Methods: We compared the analytical performance of different CTC isolation methods with regard to yield and purity: EpCAM based enrichment, leukocyte depletion and size based enrichment. EpCAM and cytokeratin 8 (KRT8) as biomarker for CTCs expression were evaluated in ccRCC cell lines as well as clinical samples.

Results: While the EpCAM based approach failed to successfully isolate tumor cells, CD45 based approaches showed intermediate recovery rates. The cell-size based Parsortix system showed highest recovery rates. EpCAM expression was low or absent in most cell lines as well as in clinical samples, whereas KRT8 was detected as a potential biomarker in ccRCC.

Conclusion: EpCAM based approaches might miss a high number of CTCs due to low or absent expression of EpCAM in ccRCC, as shown in cell lines as well as in patient samples. We identified the cell-sized based, label independent Parsortix system to be the most effective recovery system for ccRCC CTCs.
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http://dx.doi.org/10.18632/oncotarget.21197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675666PMC
October 2017

Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer.

Eur J Nucl Med Mol Imaging 2017 Sep 17;44(10):1663-1670. Epub 2017 Jun 17.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Purpose: Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with Lu-PSMA-617.

Methods: Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee.

Results: The 59 patients were treated with a total of 159 cycles (median 3 cycles, range 1-7) of Lu-PSMA-617 (median dose 6.11 GBq, IQR 5.9-6.3 GBq). The median follow-up was 24 weeks (IQR 15-36 weeks). Follow-up data for at least 12 weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32 weeks. An initial alkaline phosphatase (ALP) level <220 U/L and a PSA decline after the first cycle were associated with a longer OS (56 vs. 28 weeks, p < 0.01, and 56 vs. 29 weeks, p = 0.04, respectively). The median estimated PSA progression-free survival (PPFS) was 18 weeks. Only ALP level <220 U/L was significantly associated with a longer PPFS (41 vs. 18 weeks, p < 0.01).

Conclusions: A PSA decline after the first cycle of Lu-PSMA-617 and an initial ALP level <220 U/L were predictors of a longer OS in patients with end-stage mCRPC. An ALP level <220 U/L was additionally associated with a longer PPFS.
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http://dx.doi.org/10.1007/s00259-017-3751-zDOI Listing
September 2017

[Not Available].

Oncol Res Treat 2017 3;40 Suppl 2:8-10. Epub 2017 Apr 3.

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http://dx.doi.org/10.1159/000456167DOI Listing
October 2017

Diagnostic value of additional Ga-PSMA-PET before Ra-dichloride therapy in patients with metastatic prostate carcinoma.

Nuklearmedizin 2017 Feb 11;56(1):14-22. Epub 2017 Jan 11.

Axel Bräuer, Department of Nuclear Medicine,, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany, Phone: +49 251 8347362, Fax: +49 251 8347363, E-Mail:

Purpose: Medical imaging plays an important role in selecting patients with metastatic castration-resistant prostate cancer for Ra-dichloride therapy of bone metastases. The purpose of this study was to investigate whether Ga-PSMA-PET has incremental value over conventional imaging for selecting patients suitable for Ra-dichloride therapy.

Methods: In 27 consecutive patients referred for Ra-dichloride therapy additional Ga-PSMA-PET/CT was performed and tracer distribution was evaluated systematically with respect to the detection of visceral metastases and bone metastases with inadequate uptake on bone scintigraphy.

Results: In 4 patients (15 %) Ga-PSMA-PET revealed previously unknown visceral metastases (3 liver, 1 adrenal gland), which changed the therapeutic decision in 2 cases. PET revealed more extended tumour involvement in the bone compared to bone scintigraphy in 9 patients (33 %). In 3 of these, the mismatch was extensive enough to question suitability for Ra-dichloride therapy.

Conclusions: Additional Ga-PSMA-PET as a gatekeeper between conventional staging and Ra-dichloride therapy can provide valuable additional information with regard to visceral metastases and tumour manifestations without adequate bone mineral turnover. It may lead to a change in therapeutic management in a significant number of patients and should therefore be considered in future clinical trials.
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http://dx.doi.org/10.3413/Nukmed-0846-16-09DOI Listing
February 2017

Expression of PSMA in tumor neovasculature of high grade sarcomas including synovial sarcoma, rhabdomyosarcoma, undifferentiated sarcoma and MPNST.

Oncotarget 2017 Jan;8(3):4268-4276

Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany.

Aims: PSMA (prostate specific membrane antigen) is physiologically expressed in normal prostate tissue. It is overexpressed in prostate cancer cells and has been suggested as a target for antibody-based radioligand therapy. As PSMA expression so far has not been systematically analyzed in soft tissue tumors, the current study aims at investigating a large cohort of different subtypes.

Methods And Results: Immunohistochemistry was used to detect PSMA expression in 779 samples of soft tissue tumors and Ewing sarcoma as a primary bone malignancy. CD34 coexpression was employed to study PSMA expression in the neovasculature. PSMA expression was found in the tumor-associated neovasculature of 151/779 soft tissue/bone tumors (19.38%) and was more frequent in malignant tumors compared to tumors with intermediate or benign biological potential (p=0.078). Strong neovascular PSMA expression was predominantly observed in subsets of different sarcomas including 3/20 rhabdomyosarcomas (15%), 4/21 malignant peripheral nerve sheath tumors (19.05%), 6/16 synovial sarcomas (35.29%) and 6/33 undifferentiated pleomorphic sarcomas (18.18%).

Conclusion: We conclude that PSMA is expressed in the neovasculature of a subset of soft tissue tumors to a variable extent. Our observation of strong PSMA expression predominantly occurring in sarcomas might provide a rationale to evaluate PSMA-targeted radioligand therapy in these entities.
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http://dx.doi.org/10.18632/oncotarget.13994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354830PMC
January 2017

Excellent Response to 177Lu-PSMA-617 Radioligand Therapy in a Patient With Advanced Metastatic Castration Resistant Prostate Cancer Evaluated by 68Ga-PSMA PET/CT.

Clin Nucl Med 2017 Feb;42(2):152-153

From the Departments of *Nuclear Medicine, and †Urology University Hospital Münster, Münster, Germany.

Recently radiolabeled ligands targeting prostate specific membrane antigen (PSMA) have been introduced for diagnostics and treatment of prostate cancer. Labeled with Lutetium, PSMA radioligand therapy (RLT) is one of the most promising new treatments of metastatic castration refractory prostate cancer. We present images of Ga-PSMA PET/CT and parameters of response of a 75-year-old heavily pretreated metastatic castration refractory prostate cancer patient with extended bone metastases, showing an extraordinary biochemical response in PSA-levels concordant to SUV decline in bone metastases. Furthermore, this case shows that CT is of no use in assessing response in bone metastases of prostate cancer.
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http://dx.doi.org/10.1097/RLU.0000000000001480DOI Listing
February 2017