Publications by authors named "Tobias Maurer"

148 Publications

[Corona child studies "Co-Ki": first results of a Germany-wide register on mouth and nose covering (mask) in children].

Monatsschr Kinderheilkd 2021 Feb 22:1-10. Epub 2021 Feb 22.

Fakultät für Gesundheit/Department für Humanmedizin, Universität Witten/Herdecke, Witten/Herdecke, Deutschland.

Background: Narratives about complaints in children and adolescents caused by wearing a mask are accumulating. There is, to date, no registry for side effects of masks.

Methods: In the context of the www.co-ki.de multi-study complex, an online registry has been set up where parents, doctors, pedagogues and others can enter their observations. On 20 October 2020, 363 doctors were asked to make entries and to make parents and teachers aware of the registry.

Results: By 26 October 2020, a total of 20,353 people had taken part in the survey. The group of parents alone entered data on a total of 25,930 children. The average reported wearing time of masks was 270 min per day. Of the respondents 68% reported that children complained about impairments caused by wearing the mask. Side effects included irritability (60%), headache (53%), difficulty concentrating (50%), less happiness (49%), reluctance to go to school/kindergarten (44%), malaise (42%) impaired learning (38%) and drowsiness/fatigue (37%).

Discussion: This world's first registry for recording the effects of wearing masks in children is dedicated to a new research question. A bias with respect to the preferential documentation of particularly severely affected children or persons who are fundamentally critical of protective measures cannot be ruled out.The frequency of use and the spectrum of symptoms registered indicate the importance of the topic and call for representative surveys, randomized controlled trials with various masks and a renewed risk-benefit assessment of mask obligation in the vulnerable group of children.
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http://dx.doi.org/10.1007/s00112-021-01133-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898258PMC
February 2021

Use and Impact of Positron Emission Tomography/Computed Tomography Prior to Salvage Radiation Therapy in Men with Biochemical Recurrence After Radical Prostatectomy: A Scoping Review.

Eur Urol Oncol 2021 Feb 23. Epub 2021 Feb 23.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address:

Context: The use, common findings, and impact of modern molecular positron emission tomography (PET)/computed tomography (CT) imaging prior to salvage radiation therapy (RT) in men with biochemical recurrence after radical prostatectomy (RP) have not been evaluated comprehensively.

Objective: We performed a scoping systematic review of the literature assessing detection rates, detection patterns, changes in management, as well as changes in patient outcome resulting from molecular PET/CT imaging using three molecular tracers: F-fluciclovine, Ga prostate-specific membrane antigen (PSMA)-11, and F-DCFPyL.

Evidence Acquisition: A computerized bibliographic search of the Medline/PubMed database was carried out from inception to October 1, 2020. We included published reports and abstracts evaluating the utility of Fluciclovine, Ga-PSMA-11, and F-DCFPyL PET in the detection of recurrent disease in the post-RP, pre-salvage RT setting. Outcomes of interest were extracted and tabulated, and existing evidence was synthesized qualitatively.

Evidence Synthesis: A total of 45 studies were included in our qualitative synthesis. Detection rates were high across most studies, and there was often a clear relationship between prostate-specific antigen (PSA) level and positive imaging findings. Though limited randomized data are available, there appears to be increased sensitivity with the use of PSMA ligands compared with fluciclovine at low PSA values. Most studies have shown that only one-third to one-half of patients with detected lesions have lesions in the prostatic fossa alone. Management changes occur in nearly 50% of patients undergoing molecular imaging, and biochemical response in patients who undergo molecular PET-based RT planning appears to be statistically superior to the response in patients who undergo conventional imaging -based RT planning alone. High biochemical responses from molecular PET-based salvage RT, ranging from 45% to 94%, did not appear to come at the expense of increased genitourinary or gastrointestinal toxicity. The presence or absence of avid lesions appears to be a strong prognostic factor.

Conclusions: Molecular PET/CT imaging in the post-RP, pre-salvage RT setting often triggers management changes that result from detecting lesions in locations not typically included in consensus-driven postoperative RT fields. Ongoing trials will assess the benefit of PSMA PET in guiding salvage RT following RP and determine its impact on long-term outcomes.

Patient Summary: We reviewed and reported detection rates, detection patterns, and changes in management resulting from molecular positron emission tomography/computed tomography imaging in men with biochemically recurrent prostate cancer following radical prostatectomy. Prior to the receipt of salvage radiation therapy, molecular tracers targeting prostate-specific membrane antigen appear to be especially sensitive at identifying the place where prostate cancer has come back after surgery, which can help radiation oncologists better target the recurrent disease and potentially improve the rates of cure from prostate cancer in this setting. Future studies will determine whether these imaging tools will change cure rates and side effects, but early results are promising.
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http://dx.doi.org/10.1016/j.euo.2021.01.007DOI Listing
February 2021

Prostate-specific Membrane Antigen Radioguidance for Salvage Lymph Node Dissection in Recurrent Prostate Cancer.

Eur Urol Focus 2021 Feb 5. Epub 2021 Feb 5.

Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

Prostate-specific membrane antigen (PSMA)-based radioguidance for salvage lymph node dissection (sLND) in recurrent prostate cancer has shown promising early oncological outcomes. However, long-term outcomes are still undetermined. Future studies are needed before introducing PSMA positron emission tomography-based sLND into routine clinical practice outside of clinical trials or registries.
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http://dx.doi.org/10.1016/j.euf.2021.01.015DOI Listing
February 2021

Regional Lymph Node Metastasis on PSMA PET Correlates with Decreased BCR-Free and Therapy-free Survival after Radical Prostatectomy: A Retrospective Single-Center Single-Arm Observational Study.

J Urol 2021 Feb 4:101097JU0000000000001596. Epub 2021 Feb 4.

Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Purpose: To address the impact of preoperative PSMA PET (prostate specific membrane antigen positron emission tomography) findings prior to radical prostatectomy (RP) and pelvic lymph node dissection (PLND) on biochemical recurrence (BCR) and time to adjuvant or salvage treatment.

Materials And Methods: Between 2013 and 2017, 64 intermediate- and 166 high-risk (n=230) prostate cancer (PCa) patients received Ga-PSMA-11 PET followed by RP and PLND. BCR-free and therapy-free survival was determined. For all time to event analyses, uni- and multivariable Cox's proportional hazards models and univariable Kaplan-Meier analyses were applied, with a significance threshold of p <0.05.

Results: The overall sensitivity, specificity, positive predictive value and negative predictive value of PSMA PET for pN1 disease was 48.5%, 95.7%, 82.1% and 82.2%, respectively. Median follow up was 30.2 months. BCR occurred in 50.4% (n=116) of patients and adjuvant or salvage treatment was performed in 46.5% (n=107). Worst BCR-free and therapy-free survival was observed in pN1 patients who also exhibited PSMA PET positive LN, followed by pN1 patients without PSMA PET positive LN and patients without evidence of LN metastasis on histology and PSMA PET (median BCR-free survival 1.7 vs. 7.5 vs. >36 months, median therapy-free survival 2.6 vs. 8.9 vs. >36 months).

Conclusions: Patients with positive LN on PSMA PET prior to RP have to expect early BCR and adjuvant/salvage therapy, despite thorough PLND. Therefore, results from PSMA PET can be used for patients' consultation, more stringent follow-up as well as for planning of neo-/adjuvant therapy.
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http://dx.doi.org/10.1097/JU.0000000000001596DOI Listing
February 2021

[PSMA radioligand therapy could pose infrastructural challenges for nuclear medicine: results of a basic calculation for the capacity planning of nuclear medicine beds in the German hospital sector].

Nuklearmedizin 2021 Feb 2. Epub 2021 Feb 2.

Lehrstuhl für Management und Innovation im Gesundheitswesen, Universität Witten/Herdecke, Deutschland.

Background:  With the increasing use of the Lu-177-PSMA-RLT for the treatment of advanced castrate resistant prostate cancer (mCRPC), an estimation of the necessary therapy beds in nuclear medicine departments is of great importance in the view of the high number of cases of advanced prostate cancer, and as a basis to avoid a potentially infrastructure-related bottleneck for patient care in this field.

Methods:  The number of therapy beds available in German nuclear medicine departments was included in a basic calculation in view of the overall potential for therapy beds to be expected in the event of a possible approval of a therapeutic agent for the Lu-177-PSMA-RLT for mCRPC patients. A potential expansion of the Lu-PSMA-therapy indications was not taken into account.

Results:  The basic calculation shows for a nationwide nuclear medicine bed capacity of approx. 234 000 treatment days a relatively small bed reserve of approx. 19 000 nuclear medicine bed days, which corresponds to a reserve of 63 beds for the research question. There are regional differences in bed capacity: while for some federal states there is an under-capacity of nuclear medicine therapy beds with an approved Lu-177-PSMA-RLT, this is less the case for other federal states.

Discussion:  This basic calculation shows that the capacity of nuclear medicine therapy beds is likely to be very well utilized with a prospectively approved therapeutic agent for Lu-177-PSMA-RLT, and could even reach its limits in some German federal states. With a prospective expansion of the range of indications or the foreseeable clinical establishment of further therapeutic radiopharmaceuticals, the number of therapy beds could represent a bottleneck factor for the comprehensive patient treatment in the medium term.
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http://dx.doi.org/10.1055/a-1351-0030DOI Listing
February 2021

The Mutational Landscape of Metastatic Castration-sensitive Prostate Cancer: The Spectrum Theory Revisited.

Eur Urol 2021 Jan 5. Epub 2021 Jan 5.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Emerging data suggest that metastasis is a spectrum of disease burden rather than a binary state, and local therapies, such as radiation, might improve outcomes in oligometastasis. However, current definitions of oligometastasis are solely numerical.

Objective: To characterize the somatic mutational landscape across the disease spectrum of metastatic castration-sensitive prostate cancer (mCSPC) to elucidate a biological definition of oligometastatic CSPC.

Design, Setting, And Participants: This was a retrospective study of men with mCSPC who underwent clinical-grade sequencing of their tumors (269 primary tumor, 25 metastatic sites). Patients were classified as having biochemically recurrent (ie, micrometastatic), metachronous oligometastatic (≤5 lesions), metachronous polymetastatic (>5 lesions), or de novo metastatic (metastasis at diagnosis) disease.

Outcome Measurements And Statistical Analysis: We measured the frequency of driver mutations across metastatic classifications and the genomic associations with radiographic progression-free survival (rPFS) and time to castrate-resistant prostate cancer (CRPC).

Results And Limitations: The frequency of driver mutations in TP53 (p =  0.01), WNT (p =  0.08), and cell cycle (p =  0.04) genes increased across the mCSPC spectrum. TP53 mutation was associated with shorter rPFS (26.7 vs 48.6 mo; p =  0.002), and time to CRPC (95.6 vs 155.8 mo; p =  0.02) in men with oligometastasis, and identified men with polymetastasis with better rPFS (TP53 wild-type, 42.7 mo; TP53 mutated, 18.5 mo; p =  0.01). Mutations in TP53 (incidence rate ratio [IRR] 1.45; p =  0.004) and DNA double-strand break repair (IRR 1.61; p <  0.001) were associated with a higher number of metastases. Mutations in TP53 were also independently associated with shorter rPFS (hazard ratio [HR] 1.59; p =  0.03) and the development of CRPC (HR 1.71; p =  0.01) on multivariable analysis. This study was limited by its retrospective nature, sample size, and the use of commercially available sequencing platforms, resulting in a limited predefined set of genes examined.

Conclusions: Somatic mutational profiles reveal a spectrum of metastatic biology that helps in redefining oligometastasis beyond a simple binary state of lesion enumeration.

Patient Summary: Oligometastatic prostate cancer is typically defined as less than three to five metastatic lesions and evidence suggests that using radiation or surgery to treat these sites improves clinical outcomes. As of now, treatment decisions for oligometastasis are solely defined according to the number of lesions. However, this study suggests that tumor mutational profiles can provide a biological definition of oligometastasis and complement currently used numerical definitions.
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http://dx.doi.org/10.1016/j.eururo.2020.12.040DOI Listing
January 2021

Improving the Stratification of Patients With Intermediate-risk Prostate Cancer.

Clin Genitourin Cancer 2020 Nov 10. Epub 2020 Nov 10.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Background: Intermediate-risk prostate cancer (IR PCa) phenotypes may vary from favorable to unfavorable. National Comprehensive Cancer Network (NCCN) criteria help distinguish between those groups. We studied and attempted to improve this stratification.

Patients And Methods: A total of 4048 (NCCN favorable: 2015 [49.8%] vs. unfavorable 2033 [50.2%]) patients with IR PCa treated with radical prostatectomy were abstracted from an institutional database (2000-2018). Multivariable logistic regression models predicting upstaging and/or upgrading (Gleason Grade Group [GGG] IV-V and/or ≥ pT3 or pN1) in IR PCa were developed, validated, and directly compared with the NCCN IR PCa stratification.

Results: All 4048 patients were randomly divided between development (n = 2024; 50.0%) and validation cohorts (n = 2024; 50.0%). The development cohort was used to fit basic (age, prostate-specific antigen, clinical T stage, biopsy GGG, and percentage of positive cores [all P < .001]) and extended models (age, prostate-specific antigen, clinical T stage, biopsy GGG, prostate volume, and percentage of tumor within all biopsy cores [all P < .001]). In the validation cohort, the basic and the extended models were, respectively, 71.4% and 74.7% accurate in predicting upstaging and/or upgrading versus 66.8% for the NCCN IR PCa stratification. Both models outperformed NCCN IR PCa stratification in calibration and decision curve analyses (DCA). Use of NCCN IR PCa stratification would have misclassified 20.1% of patients with ≥ pT3 or pN1 and/or GGG IV to V versus 18.3% and 16.4% who were misclassified using the basic or the extended model, respectively.

Conclusion: Both newly developed and validated models better discriminate upstaging and/or upgrading risk than the NCCN IR PCa stratification.
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http://dx.doi.org/10.1016/j.clgc.2020.11.003DOI Listing
November 2020

Salvage Surgery in Patients with Local Recurrence After Radical Prostatectomy.

Eur Urol 2020 Dec 11. Epub 2020 Dec 11.

Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

Background: Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, isolated local recurrence after radical prostatectomy (RP) can be delineated accurately.

Objective: To describe and evaluate surgical technique, biochemical response, and therapy-free survival (TFS) after salvage surgery in patients with local recurrence in the seminal vesicle bed.

Design, Setting, And Participants: We retrospectively assessed 40 patients treated with open salvage surgery in two centres (11/2014-02/2020). All patients presented with biochemical recurrence (BCR) after RP with a singular local recurrence at PSMA PET imaging. Thirty-three (82.5%) patients received previous salvage radiation therapy.

Surgical Procedure: Open salvage surgery with PSMA radioguidance.

Measurements: Prostate-specific antigen (PSA) nadir and percentage of patients with complete biochemical response (cBR) without further treatment (PSA < 0.2 ng/ml) after 6-16 wk were assessed. BCR-free survival and TFS were calculated using Kaplan-Meier estimates. Clavien-Dindo complications were evaluated.

Results And Limitations: Prior to salvage surgery, median PSA was 0.9 ng/ml (interquartile range [IQR]: 0.5-1.7 ng/ml). Postoperatively, median PSA nadir was 0.1 ng/ml (IQR: 0-0.4 ng/ml). In 31 (77.5%) patients, cBR was observed. During the median follow-up of 24.4 months, 22 (55.0%) patients experienced BCR and 12 (30.0%) received further therapy. At 1 yr of follow-up, BCR-free survival rate was 62.2% and TFS rate was 88.3%. Three (7.5%) Clavien-Dindo grade III complications were observed. The main limitations are the retrospective design, short follow-up, and lack of a control group.

Conclusions: Salvage surgery of local recurrence within the seminal vesicle bed is feasible. It may present an opportunity in selected, locally recurrent patients to prolong BCR-free survival and increase TFS. Further studies are needed to confirm our findings.

Patient Summary: We looked at the outcomes from prostate cancer patients with locally recurrent disease after radical prostatectomy and radiotherapy. We found that surgery in well-selected patients may be an opportunity to prolong treatment-free survival.
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http://dx.doi.org/10.1016/j.eururo.2020.11.012DOI Listing
December 2020

A DROP-IN Gamma Probe for Robot-assisted Radioguided Surgery of Lymph Nodes During Radical Prostatectomy.

Eur Urol 2021 Jan 14;79(1):124-132. Epub 2020 Nov 14.

Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Urology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address:

Background: The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting.

Objective: To confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance.

Design, Setting, And Participants: Twenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre.

Surgical Procedure: After intraprostatic injection of indocyanine green (ICG)-Tc-nanocolloid (n = 12) or Tc-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging.

Measurements: Intraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo).

Results And Limitations: Overall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions.

Conclusions: Owing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting.

Patient Summary: Radioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations.
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http://dx.doi.org/10.1016/j.eururo.2020.10.031DOI Listing
January 2021

Positive predictive value and correct detection rate of F-rhPSMA-7 PET in biochemically recurrent prostate cancer validated by composite reference standard.

J Nucl Med 2020 Nov 13. Epub 2020 Nov 13.

School of Medicine, Department of Nuclear Medicine, Technische Universität München, Germany.

The objective of this retrospective study was to assess the detection rate (DR), positive predictive value (PPV) and correct detection rate (CDR) of F-rhPSMA-7 PET/CT in biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) using composite validation. F-rhPSMA-7 PET/CT scans of patients with BCR between July 2017 and June 2018 were retrospectively reviewed. All suspicious lesions were recorded. Reference standard was histopathology or combinations of histopathology, imaging or prostate-specific antigen (PSA) follow up, defined as composite reference standard. DR was calculated as the proportion of PSMA PET positive patients to all patients independent of the reference standard, while the CDR was the percentage of patients who had at least one true positive PSMA PET lesion localized that corresponded with the reference standard. The PPV was defined as the proportion of patients who had true positive to all positive findings. The correlation between DR and patient characteristics was evaluated. A total of 532 patients with a median PSA level of 0.97 ng/mL (IQR: 0.41-2.46 ng/mL) were included. Out of these, 162 patients had composite follow-up at a median duration of 5.6 months (range 1.1-14.2 months). The proportion of patients who had no lesion visualized on PET/CT, localized disease, and any distant metastases (M1) were 20%, 43% and 37%, respectively. PET DR among all patients was 80%. On per-patient basis, the PPV of F-rhPSMA-7 PET/CT in the composite cohort was 88%, and the CDR was 70%. The PPV in the histopathology-proven cohort was 91%, and the CDR in this subgroup was 73%. In patients with PSA levels ≥1 ng/mL the DR and PPV were 90% and 91%, respectively resulting in a CDR of 82%. In patients with PSA levels <1 ng/mL the DR and PPV were 69% and 85%, respectively resulting in a CDR of 59%. There was a significant positive correlation between F-rhPSMA-7 PET/CT detection efficacy and stratified PSA levels ( = 0.005), as well as PSA nadir after prostatectomy (P<0.001). F-rhPSMA-7 PET/CT offers high PPV in BCR after RP. Its CDR is dependent on the pre-scan PSA value with excellent CDR in patients with PSA ≥1 ng/mL.
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http://dx.doi.org/10.2967/jnumed.120.255661DOI Listing
November 2020

[Corona in Children: the Co-Ki Study].

Monatsschr Kinderheilkd 2020 Nov 3:1-6. Epub 2020 Nov 3.

Lehrstuhl für Medizintheorie, Integrative und Anthroposophische Medizin, Universität Witten/Herdecke, Alfred-Herrhausen-Straße 50, 58448 Witten, Deutschland.

Background: In Germany over 80% of children and adolescents are in the ambulatory care of registered pediatricians. These have a specific perspective on the COVID-19 pandemic.

Methods: For this reason, this professional group initiated a central recording of case numbers, individual case descriptions and observations on infections and illnesses with SARS-CoV‑2 (www.co-ki.de).

Results: So far 557 pediatricians have participated. Together they care for ca. 670,000 children. They reported 9803 children who presented as suspected cases. The pediatricians themselves had a clinical suspicion of SARS-CoV‑2 infections in 3654 children. In 7707 children PCR tests were carried out using nose/throat swabs of which 198 (2.6%) were positive. In addition, 731 children were tested for SARS-CoV‑2 antibodies with detection in 82 cases (11.2%). Despite initially positive PCR tests, 47 children had a negative antibody test at least 2 weeks later. Our query as to infections of adults by children yielded only one case, which a telephone enquiry revealed as unlikely.

Discussion: From an outpatient pediatric perspective COVID-19 is rare. There was no convincing evidence that children are a relevant source of infection for SARS-CoV‑2 nor that they are relevantly at risk.
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http://dx.doi.org/10.1007/s00112-020-01050-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607899PMC
November 2020

Differences between rural and urban prostate cancer patients.

World J Urol 2020 Nov 5. Epub 2020 Nov 5.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Background: We hypothesized that the residency status (rural area [RA] vs urban clusters [UC] vs urban areas [UA]) affects stage and cancer-specific mortality (CSM) in contemporary newly diagnosed prostate cancer (PCa) patients of all stages, regardless of treatment.

Methods: Newly diagnosed PCa patients with available residency status were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Propensity-score (PS) matching, cumulative incidence plots, multivariate competing-risks regression (CRR) models were used.

Results: Of 531,468 PCa patients of all stages, 6653 (1.3%) resided in RA, 50,932 (9.6%) in UC and 473,883 (89.2%) in UA. No statistically significant or clinically meaningful differences in stage at presentation or CSM were recorded. Conversely, 10-year other cause-mortality (OCM) rates were 27.2% vs 23.7% vs 18.9% (p < 0.001) in RA vs UC vs UA patients, respectively. In CRR models, RA (subhazard ratio [SHR] 1.38; p < 0.001) and UC (SHR 1.18; p < 0.001) were independent predictors for higher OCM relative to UA. These differences remained statistically significant in fully PS-adjusted multivariate CRR models.

Conclusion: RA, and to a lesser extent UC, PCa patients are at higher risk of OCM than UA patients. Higher OCM may indicate shorter life expectancy and should be considered in treatment decision making.
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http://dx.doi.org/10.1007/s00345-020-03483-7DOI Listing
November 2020

Outcomes of minimally invasive partial nephrectomy among very elderly patients: report from the RESURGE collaborative international database.

Cent European J Urol 2020 8;73(3):273-279. Epub 2020 Sep 8.

Unit of Urology, Division of Experimental Oncology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy.

The aim of the study was to perform a comprehensive investigation of clinical outcomes of robot-assisted partial nephrectomy (RAPN) or laparoscopic partial nephrectomy (LPN) in elderly patients presenting with a renal mass. The REnal SURGery in Elderly (RESURGE) collaborative database was queried to identify patients aged 75 or older diagnosed with cT1-2 renal mass and treated with RAPN or LPN. Study outcomes were: overall complications (OC); warm ischemia time (WIT) and 6-month estimated glomerular filtration rate (eGFR); positive surgical margins (PSM), disease recurrence (REC), cancer-specific mortality (CSM) and other-cause mortality (OCM). Descriptive statistics, Kaplan-Meier, smoothed Poisson plots and logistic and linear regression models (MVA) were used. Overall, 216 patients were included in this analysis. OC rate was 34%, most of them being of low Clavien grade. Median WIT was 17 minutes and median 6-month eGFR was 54 ml/min/1.73 m. PSM rate was 5%. After a median follow-up of 20 months, the 5-year rates of REC, CSM and OCM were 4, 4 and 5%, respectively. At MVA predicting perioperative morbidity, RAPN relative to LPN (odds ratio [OR] 0.33; p <0.0001) was associated with lower OC rate. At MVA predicting functional outcomes, RAPN relative to LPN was associated with shorter WIT (estimate [EST] -4.09; p <0.0001), and with higher 6-month eGFR (EST 6.03; p = 0.01). In appropriately selected patients with small renal masses, minimally-invasive PN is associated with acceptable perioperative outcomes. The use of a robotic approach over a standard laparoscopic approach can be advantageous with respect to clinically relevant outcomes, and it should be preferred when available.
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http://dx.doi.org/10.5173/ceju.2020.0179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587491PMC
September 2020

Oncological outcomes of pathologically organ-confined, lymph node-positive prostate cancer after radical prostatectomy.

Urol Oncol 2020 Oct 20. Epub 2020 Oct 20.

Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Background: The aim of this study was to investigate the impact of lymph-node involvement on oncological outcomes in patients with pathologically organ-confined prostate cancer (pT2 CaP) after radical prostatectomy (RP).

Methods: We retrospectively analyzed 9,631 pT2 CaP patients who underwent RP at a single institution between 1998 and 2018. Kaplan-Meier plots and Cox regression models (CRMs) assessed biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS) according to N-stage. In subgroup analyses of N1 patients, Kaplan-Meier plots and CRMs were stratified according to adjuvant treatment.

Results: Of 9,631 pT2 staged patients, 241 (2.5%) harbored lymph-node metastases after RP (pN1). The median follow-up was 60.8 months. No pT2 N1-staged patient died due to CaP. The 5-year BCR-free survival rates were 54.7 vs. 88.4% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). The 5-year MFS rates were 92.5 vs. 98.9% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). Within pT2 N1 patients, presence of ≥3 positive lymph nodes was an independent risk factor for BCR (hazard ratio [HR] 3.4, P < 0.001) and for metastatic progression (HR 1.7, P = 0.04). Finally, 3-year BCR-free survival was improved in pT2 N1 patients treated with adjuvant radiation therapy (87.1% vs. 63.7% for patients who received other treatment options [P < 0.001]).

Conclusion: Patients with pathologically organ-confined but lymph node-positive CaP exhibited favorable oncological outcomes after RP. Presence of ≥3 positive LNs predicted higher rates of BCR and metastatic progression. In consequence, in pT2 N1 patients treated with RP with ≥3 positive LNs, adjuvant treatment may be considered.9.
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http://dx.doi.org/10.1016/j.urolonc.2020.10.010DOI Listing
October 2020

KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy.

Prostate Cancer Prostatic Dis 2020 Sep 25. Epub 2020 Sep 25.

Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Munich, Germany.

Background: Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than histopathology. We aimed to prospectively evaluate six candidate gene markers for detection of pelvic LN metastases and to determine their ability to predict biochemical recurrence-free survival (bRFS) in patients treated with RP.

Methods: The expression of kallikrein 2, 3, and 4 (KLK2, KLK3, and KLK4), prostate-specific membrane antigen (PSMA), transmembrane serine protease 2 (TMPRSS2) and transient receptor potential cation channel subfamily M member 8 (TRPM8) was assessed using qPCR. We analyzed LNs from 111 patients (intermediate PC, n = 32 (29%); high-risk PC, n = 79 (71%)) who underwent RP and extended pelvic lymph-node dissection without neoadjuvant treatment.

Results: Overall, 2411 LNs were examined by molecular and histopathologic examination. Histopathology detected 69 LN metastases in 28 (25%) patients. KLK2 and KLK3 diagnostically performed best and classified all pN1-patients correctly as molecular node-positive (molN1/pN1). The concordance on LN level was best for KLK3 (96%). KLK2, KLK3, KLK4, PSMA, TMPRSS2, and TRPM8 reclassified 27 (24%), 32 (29%), 29 (26%), 8 (7%), 13 (12%), and 23 (21%) pN0-patients, respectively, as node-positive (pN0/molN1). On multivariable cox regression analysis molecular LN status (molN1 vs. molN0) using KLK3 (HR 4.0, p = 0.04) and TMPRSS2 (HR 5.1, p = 0.02) were independent predictors of bRFS. Median bRFS was shorter in patients with only molecular positive LNs (molN1/pN0) for KLK3 (24 months, p = 0.001) and for TMPRSS2 (12 months, p < 0.001) compared to patients with negative nodes (molN0/pN0) (median bRFS not reached).

Conclusions: For diagnostic purposes, KLK3 showed highest concordance with histopathology for detection of LN metastases in PC patients undergoing RP. For prognostic purposes, KLK3 and TMPRSS2 expression were superior to histopathologic LN status and other transcripts tested for molecular LN status. We suggest a combined KLK3/TMPRSS2 panel as a valuable diagnostic and prognostic tool for molecular LN analysis.
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http://dx.doi.org/10.1038/s41391-020-00283-3DOI Listing
September 2020

First experience using F-18-flubrobenguane PET imaging in patients with the suspicion of pheochromocytoma or paraganglioma.

J Nucl Med 2020 Aug 28. Epub 2020 Aug 28.

University Hospital Essen, Germany.

Pheochromocytomas and paragangliomas are a rare tumor entity originating from adreno-medullary chromaffin cells in the adrenal medulla or in sympathetic, paravertebral ganglia outside the medulla. Especially small lesions are difficult to detect by conventional CT or MR imaging and even by SPECT imaging with currently available radiotracers (e.g. MIBG). The novel PET-radiotracer F-18-flubrobenguane could change the diagnostic paradigm in suspected pheochromocytomas and paragangliomas due to its homology to MIBG and the general advantages of PET-imaging. Aim of this retrospective analysis was to evaluate F-18-flubrobenguane in pheochromocytomas and paragangliomas and to investigate the biodistribution in patients. 24 Patients with suspected pheochromocytoma and paraganglioma underwent PET/CT or PET/MRI at 63±24 min p.i. after injection of 256±33 MBq F-18-flubrobenguane. SUVmean and SUV values of organs were measured with spherical volume-of-interests. Threshold segmented volume-of-interests were used to measure SUVmean/max of the tumor lesions. One reader evaluated all cross-sectional imaging datasets (CT or MRI) separately as well as the PET hybrid datasets and reported lesion number and size. A three point-scale indicating the diagnostic certainty for a positive lesion was assigned. F-18-flubrobenguane showed a reproducible, stable biodistribution with highest values of SUV/mean in the thyroid gland (30.3±2.2/22.5±1.6), pancreas (12.2±0.8/9.5±0.7), tumor lesions (16.8±1.7/10.1±1.1) and the lowest SUV/mean values in muscle (1.1±0.06/0.7±0.04) and lung (2.5±0.17/1.85±0.13). In a subgroup analysis both pheochromocytoma and paraganglioma lesions showed a significantly higher average SUVmean compared to healthy adrenal glands (11.9±2.0 vs 9.9±1.5 vs 3.7±0.2). In total 47 lesions were detected. The reader reported more and smaller lesions with higher certainty in PET hybrid imaging compared to conventional imaging, however, statistical significance was not reached. 61% (14/23) of the 23 (23/47, 49%) lesions smaller than 1 cm were found on hybrid imaging only. Our preliminary data suggest F-18-flubrobenguane PET as a new effective staging tool in patients with suspected pheochromocytoma and paraganglioma. Major advantages are the fast acquisition and high spatial resolution of PET imaging and intense uptake in tumor lesions facilitating lesion detection. Further studies are warranted to define its role particularly in comparison to standard diagnostic procedures such as MRI or I-123-MIBG SPECT/CT.
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http://dx.doi.org/10.2967/jnumed.120.248021DOI Listing
August 2020

[68Ga-PSMA-11 PET/mpMRI for local detection of primary prostate cancer in men with a negative prior biopsy].

Aktuelle Urol 2020 Aug 27. Epub 2020 Aug 27.

Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München.

Introduction And Objective:  Multiparametric MRI (mpMRI) represents the current gold standard for the detection of primary prostate cancer (PC) after a negative biopsy. PSMA PET imaging has been introduced in the diagnostic work-up of PC with high accuracy, but is currently mainly utilised in the setting of biochemical recurrence. This study aimed to determine the efficacy of combined Ga-PSMA-11 PET/mpMRI imaging to detect PC in patients with previously negative prostate biopsies.

Methods:  A total of 57 patients who had undergone at least one prior negative prostate biopsy were included in this retrospective analysis. All patients underwent Ga-PSMA-11 PET/mpMRI imaging of the prostate. mpMRI was evaluated according to the PIRADS classification system and Ga-PSMA-11 PET was rated on a 5-point Likert scale (1: PC highly unlikely; 2: PC unlikely; 3: presence of PC is equivocal; 4: PC likely; 5: PC highly likely). All patients received a systematic random biopsy as well as a targeted transrectal biopsy of lesions suspicious on imaging. Imaging and histological biopsy outcomes were compared on a per-patient basis.

Results:  In the histological analysis, 35/57 (61.4 %) patients harboured PC lesions. In patients with biopsy-proven PC, 21/35 (60.0 %) had a PI-RADS 4 or 5 lesion on mpMRI and 28 /35 (80.0 %) had a PET rating of 4 or 5. Combined Ga-PSMA-11 PET/mpMRI missed only one patient with a Gleason score (GS) 7a tumour (rating of 1 or 2 in both PET and mpMRI). Limitations include the retrospective analysis as well as possible false negative biopsy results even in a fusion biopsy setting.

Conclusion:  In this initial analysis, the combined Ga-PSMA-11 PET/mpMRI proved to be a valuable imaging tool to guide prostate biopsies for the detection of PC in patients with a negative prior biopsy. In this approach, Ga-PSMA-11 PET and mpMRI show partially complementary findings that enhance the detection of PC lesions.
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http://dx.doi.org/10.1055/a-1198-2305DOI Listing
August 2020

Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer.

Eur J Nucl Med Mol Imaging 2021 Feb 2;48(2):469-476. Epub 2020 Jul 2.

Department of Urology, Skåne University Hospital, Malmö, Sweden.

Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is used for (re)staging prostate cancer (PCa) and as a biomarker for evaluating response to therapy, but lacks established response criteria. A panel of PCa experts in nuclear medicine, radiology, and/or urology met on February 21, 2020, in Amsterdam, The Netherlands, to formulate criteria for PSMA PET/CT-based response in patients treated for metastatic PCa and optimal timing to use it.

Methods: Panelists received thematic topics and relevant literature prior to the meeting. Statements on how to interpret response and progression on therapy in PCa with PSMA PET/CT and when to use it were developed. Panelists voted anonymously on a nine-point scale, ranging from strongly disagree (1) to strongly agree (9). Median scores described agreement and consensus.

Results: PSMA PET/CT consensus statements concerned utility, best timing for performing, criteria for evaluation of response, patients who could benefit, and handling of radiolabeled PSMA PET tracers. Consensus was reached on all statements. PSMA PET/CT can be used before and after any local and systemic treatment in patients with metastatic disease to evaluate response to treatment. Ideally, PSMA PET/CT imaging criteria should categorize patients as responders, patients with stable disease, partial response, and complete response, or as non-responders. Specific clinical scenarios such as oligometastatic or polymetastatic disease deserve special consideration.

Conclusions: Adoption of PSMA PET/CT should be supported by indication for appropriate use and precise criteria for interpretation. PSMA PET/CT criteria should categorize patients as responders or non-responders. Specific clinical scenarios deserve special consideration.
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http://dx.doi.org/10.1007/s00259-020-04934-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835167PMC
February 2021

A CT-based radiomics model to detect prostate cancer lymph node metastases in PSMA radioguided surgery patients.

Eur J Nucl Med Mol Imaging 2020 12 28;47(13):2968-2977. Epub 2020 May 28.

Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675, Munich, Germany.

Purpose: In recurrent prostate carcinoma, determination of the site of recurrence is crucial to guide personalized therapy. In contrast to prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) imaging, computed tomography (CT) has only limited capacity to detect lymph node metastases (LNM). We sought to develop a CT-based radiomic model to predict LNM status using a PSMA radioguided surgery (RGS) cohort with histological confirmation of all suspected lymph nodes (LNs).

Methods: Eighty patients that received RGS for resection of PSMA PET/CT-positive LNMs were analyzed. Forty-seven patients (87 LNs) that received inhouse imaging were used as training cohort. Thirty-three patients (62 LNs) that received external imaging were used as testing cohort. As gold standard, histological confirmation was available for all LNs. After preprocessing, 156 radiomic features analyzing texture, shape, intensity, and local binary patterns (LBP) were extracted. The least absolute shrinkage and selection operator (radiomic models) and logistic regression (conventional parameters) were used for modeling.

Results: Texture and shape features were largely correlated to LN volume. A combined radiomic model achieved the best predictive performance with a testing-AUC of 0.95. LBP features showed the highest contribution to model performance. This model significantly outperformed all conventional CT parameters including LN short diameter (AUC 0.84), LN volume (AUC 0.80), and an expert rating (AUC 0.67). In lymph node-specific decision curve analysis, there was a clinical net benefit above LN short diameter.

Conclusion: The best radiomic model outperformed conventional measures for detection of LNM demonstrating an incremental value of radiomic features.
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http://dx.doi.org/10.1007/s00259-020-04864-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680305PMC
December 2020

PSMA-Ligand PET for Early Castration-Resistant Prostate Cancer: A Retrospective Single-Center Study.

J Nucl Med 2021 Jan 22;62(1):88-91. Epub 2020 May 22.

Department of Nuclear Medicine, University of Duisburg-Essen, and German Cancer Consortium-University Hospital Essen, Essen, Germany

The low detection rate of conventional imaging and unspecific fluctuations in prostate-specific antigen can hamper early diagnosis of castration-resistant prostate cancer (CRPC). We thus assessed the value of prostate-specific membrane antigen (PSMA) PET/CT in the detection of early CRPC (prostate-specific antigen ≤ 3 ng/mL). We identified 55 patients with early CRPC from our institutional database. PSMA PET/CT and its CT component were interpreted independently by 3 masked readers. The primary endpoint was the per-patient detection rate; secondary endpoints were interobserver agreement and predictors of PET positivity. PSMA PET/CT was positive in 41 of 55 (75%) patients. Sixteen of 55 (29%) patients had local disease only, and 25 of 55 (45%) had M1 disease. Overall, PSMA PET/CT interobserver agreement was substantial by Landis and Koch criteria (Fleiss κ = 0.77). PSMA PET/CT localized prostate cancer lesions in 75% of patients and M1 disease in 45%. Detection of early CRPC facilitates disease-delaying therapies for local or oligometastatic disease. PSMA PET/CT is of value in early CRPC and should be included in the CRPC entry criteria of the European Association of Urology and Prostate Cancer Working Group 3.
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http://dx.doi.org/10.2967/jnumed.120.245456DOI Listing
January 2021

Final results of the PräVAC trial: prevention of wound complications following inguinal lymph node dissection in patients with penile cancer using epidermal vacuum-assisted wound closure.

World J Urol 2021 Feb 5;39(2):613-620. Epub 2020 May 5.

Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Ismaningerstr. 22, 81375, Munich, Germany.

Purpose: Inguinal lymphadenectomy in penile cancer is associated with a high rate of wound complications. The aim of this trial was to prospectively analyze the effect of an epidermal vacuum wound dressing on lymphorrhea, complications and reintervention in patients with inguinal lymphadenectomy for penile cancer.

Patients And Methods: Prospective, multicenter, randomized, investigator-initiated study in two German university hospitals (2013-2017). Thirty-one patients with penile cancer and indication for bilateral inguinal lymph node dissection were included and randomized to conventional wound care on one side (CONV) versus epidermal vacuum wound dressing (VAC) on the other side.

Results: A smaller cumulative drainage fluid volume until day 14 (CDF) compared to contralateral side was observed in 15 patients (CONV) vs. 16 patients (VAC), with a median CDF 230 ml (CONV) vs. 415 ml (VAC) and a median maximum daily fluid volume (MDFV) of 80 ml (CONV) vs. 110 ml (VAC). Median time of indwelling drainage: 7 days (CONV) vs. 8 days (VAC). All grade surgery-related complications were seen in 74% patients (CONV) vs. 74% patients (VAC); grade 3 complications in 3 patients (CONV) vs. 6 patients (VAC). Prolonged hospital stay occurred in 32% patients (CONV) vs. 48% patients (VAC); median hospital stay was 11.5 days. Reintervention due to complications occurred in 45% patients (CONV) vs. 42% patients (VAC).

Conclusions: In this prospective, randomized trial we could not observe a significant difference between epidermal vacuum treatment and conventional wound care.
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http://dx.doi.org/10.1007/s00345-020-03221-zDOI Listing
February 2021

Combined systematic versus stand-alone multiparametric MRI-guided targeted fusion biopsy: nomogram prediction of non-organ-confined prostate cancer.

World J Urol 2021 Jan 5;39(1):81-88. Epub 2020 Apr 5.

Martini-Klinik, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.

Objective: Based on unfavorable oncological and functional outcomes of non-organ-confined (NOC) prostate cancer (PCa), defined as ≥ pT3, pN1 or both, we aimed to develop a NOC prediction tool based on multiparametric MRI-guided targeted fusion biopsy (TBx).

Materials And Methods: Analyses were restricted to 594 patients with simultaneous PCa detection at systematic biopsy (SBx), TBx and subsequent radical prostatectomy (RP) at our institution. Development (n = 396; cohort 1) and validation cohorts (n = 198; cohort 2) were used to develop and validate the NOC nomogram. A head-to-head comparison was performed between stand-alone TBx model and combined TBx/SBx model. Second validation was performed in patients with positive TBx, but negative SBx (n = 193; cohort 3).

Results: The most parsimonious TBx model included three independent predictors of NOC: pretreatment PSA (OR 1.05 95% CI: 1.01-1.08), highest TBx-detected Gleason pattern (3 + 3 [REF] vs. ≥ 4 + 5; OR 9.3 95% CI 3.8-22) and presence of TBx-detected perineural invasion (OR 2.2 95% CI: 1.3-3.6). The combined TBx/SBx model had the same predictors. For the stand-alone TBx and combined TBx/SBx model, external validation yielded accuracy of 76.5% (95% CI: 69.3-83.1) and 76.6% (95% CI: 69.4-83.6) within cohort 2. The external validation of the stand-alone TBx model yielded 72.4% (95% CI: 65.0-79.6) accuracy within cohort 3.

Conclusion: Our stand-alone TBx-based nomogram can identify PCa patients at the risk of NOC, using three simple variables, with the similar accuracy as the TBx/SBx-based model. It is non-inferior to combined TBx/SBx-based model and performs with sufficient accuracy in specific patients with positive TBx, but negative SBx.
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http://dx.doi.org/10.1007/s00345-020-03176-1DOI Listing
January 2021

[Salvage lymph node dissection for nodal recurrent prostate cancer].

Aktuelle Urol 2020 06 26;51(3):258-264. Epub 2020 Mar 26.

Universitätsklinikum Hamburg-Eppendorf, Martini-Klinik, Hamburg.

Recent advances in functional imaging, such as prostate-specific membrane antigen positron emission tomography (PSMA PET/CT), provide earlier detection of nodal recurrent prostate cancer. Current studies on metastasis-directed therapy in patients with node-only recurrence suggest a positive influence on the prognosis in selected patients. Nevertheless, most studies are retrospective and, due to a lack of high-level evidence, salvage lymph node dissection (SLND) is not recommended by current guidelines.The aim of this work is to provide a critical summary of the current data on SLND in patients with nodal recurrent prostate cancer with a focus on imaging procedures, extent of SLND and oncological outcome.European guidelines recommend the use of choline or PSMA PET/CT imaging if prostate cancer recurrence is suspected. PSMA PET/CT is superior to choline PET/CT in sensitivity and specificity and should be the preferred approach. Nevertheless, if SLND is performed, common practice is bilateral SLND - even if only unilateral lymph node involvement is detected by PSMA PET/CT. However, unilateral SLND can also be considered. A randomised prospective trial (ProSTone) is being initiated for clarification.PSMA radioguided surgery seems to be a new promising surgical approach. It facilitates the intraoperative detection of lymph node metastases. However, long-term data are still awaited.All in all, SLND achieves a respectable biochemical response rate in carefully selected patients. Nevertheless, prospective studies are necessary in the future in order to define the clinical usefulness more precisely.
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http://dx.doi.org/10.1055/a-1132-5180DOI Listing
June 2020

Pre-test Ga-PSMA-ligand PET/CT positivity in early biochemical recurrent prostate cancer after radical prostatectomy-validation of a prediction model.

EJNMMI Res 2020 Feb 3;10(1). Epub 2020 Feb 3.

School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Objectives: The aim of this study was the validation of a recently established comprehensive and compact prediction model for Ga-PSMA-11-ligand positron-emission tomography (PET) positivity with an independent subsequent patient series.

Methods: A total of 292 consecutive patients with early biochemical recurrence after radical prostatectomy and PSA values between 0.2 and 1 ng/ml who underwent Ga-PSMA-11-ligand PET/computed tomography (CT) between January 2016 and June 2017 were retrospectively included. The cohort was divided into a very low PSA value (0.2-0.5 ng/ml, n = 151) and a low PSA value (> 0.5-1 ng/ml, n = 141) subgroup. First, pre-test positivity probabilities for each patient were calculated according to the previously published comprehensive prediction model using all clinical variables (PSA value, ISUP grade group, T- and N-stage, patient under androgen deprivation therapy (ADT), previous radiation therapy) and the compact model using just the most predictive factors PSA value, ADT, and grade group. Then, all Ga-PSMA-11-ligand PET/CTs were analysed by one experienced nuclear medicine physician, and the results were correlated to the calculated pre-test probabilities.

Results: In the very low PSA value subgroup, mean pre-test probability for positive findings in Ga-PSMA-11-ligand PET/CT was 57% (95% CI 55-60%) according to the compact model and 59% (95% CI 56-61%) according to the comprehensive model. In the low PSA value subgroup, mean pre-test probability was 72% (95% CI 70-74%) in the compact model and 74% (95% CI 72-76%) in the comprehensive model. After image analysis, 59% (89/151) of the patients in the very low PSA value subgroup revealed positive imaging findings. Seventy-nine percent (112/141) of the patients in the low PSA value subgroup presented with positive findings in the Ga-PSMA-11-ligand PET/CT. The accuracy (AUC) of the prediction models was 0.71 (95% CI 0.65-0.78) for the compact model and 0.74 (95% CI 0.68-0.80) for the comprehensive model.

Conclusion: External validation of the recently proposed prediction models showed a high concordance of the calculated pre-test probabilities and actual Ga-PSMA-11-ligand PET/CT findings in the validation cohort confirming the prediction models' ability to determine the presence of a positive lesion at Ga-PSMA-11-ligand PET. However, the predictive accuracy of the nomogram itself is suboptimal and should be used with caution. Furthermore, the model's generalizability may be hampered due to the study design (in-house validation). Nevertheless, given the limited health resources and the costs of hybrid imaging techniques, prediction models might be a benefit in patient selection.
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http://dx.doi.org/10.1186/s13550-020-0595-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997317PMC
February 2020

Image-Guided Surgery: Are We Getting the Most Out of Small-Molecule Prostate-Specific-Membrane-Antigen-Targeted Tracers?

Bioconjug Chem 2020 02 6;31(2):375-395. Epub 2020 Jan 6.

Interventional Molecular Imaging Laboratory, Department of Radiology , Leiden University Medical Center , 2333 ZA Leiden , The Netherlands.

Expressed on virtually all prostate cancers and their metastases, the transmembrane protein prostate-specific membrane antigen (PSMA) provides a valuable target for the imaging of prostate cancer. Not only does PSMA provide a target for noninvasive diagnostic imaging, e.g., PSMA-positron emission tomography (PSMA-PET), it can also be used to guide surgical resections of PSMA-positive lesions. The latter characteristic has led to the development of a plethora of PSMA-targeted tracers, i.e., radiolabeled, fluorescent, or hybrid. With image-guided surgery applications in mind, this review discusses these compounds based on clinical need. Here, the focus is on the chemical aspects (e.g., imaging label, spacer moiety, and targeting vector) and their impact on in vitro and in vivo tracer characteristics (e.g., affinity, tumor uptake, and clearance pattern).
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033908PMC
February 2020

F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy.

J Nucl Med 2020 05 13;61(5):696-701. Epub 2019 Dec 13.

Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

F-labeled prostate-specific membrane antigen (PSMA) PET tracers are increasingly used in preference to Ga-PSMA-11 for restaging biochemical recurrence (BCR) of prostate cancer. They are associated with longer half-lives, larger-scale production, and lower positron range than their Ga-labeled counterparts. Here, we describe the efficacy of an F-labeled radiohybrid PSMA, rhPSMA-7, a novel theranostic PSMA-targeting agent for imaging BCR of prostate cancer. Datasets from 261 consecutive patients with noncastrate BCR after radical prostatectomy who underwent F-rhPSMA-7 PET/CT at our institution between June 2017 and March 2018 were reviewed retrospectively. All lesions suspected of being recurrent prostate cancer were recorded. The detection rate for sites of presumed recurrence was correlated with patients' prostate-specific antigen (PSA) level, primary Gleason score, and prior therapy (androgen deprivation therapy and external-beam radiation therapy). The 261 patients had a median PSA level of 0.96 ng/mL (range, 0.01-400 ng/mL). The median injected activity of F-rhPSMA-7 was 336 MBq, with a median uptake time of 76 min. In total, 211 patients (81%) showed pathologic findings on F-rhPSMA-7 PET/CT. The detection rates were 71% (42/59), 86% (44/51), 86% (42/49), and 95% (76/80) at PSA levels of 0.2 to <0.5 ng/mL, 0.5 to <1 ng/mL, 1 to <2 ng/mL, and ≥2 ng/mL, respectively. In 32% patients (7/22) with a PSA of less than 0.2 ng/mL, suggestive lesions were present. F-rhPSMA-7 PET/CT revealed local recurrence in 43% of patients (113). Lymph node metastases were present in the pelvis in 42% of patients (110), in the retroperitoneum in 17% (45), and in a supradiaphragmatic location in 8.0% (21). Bone and visceral metastases were detected in 21% (54) and 3.8% (10), respectively. Detection efficacy was not influenced by prior external-beam radiation therapy (79.1% vs. 82.1%, = 0.55), androgen deprivation therapy within the 6 mo preceding imaging (80.6% vs. 80.9%, = 0.54), or primary Gleason score (77.9% for ≤7 vs. 82.6% for ≥8, = 0.38). F-rhPSMA-7 PET/CT offers high detection rates in early BCR after radical prostatectomy, especially among patients with low PSA values.
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http://dx.doi.org/10.2967/jnumed.119.234914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198386PMC
May 2020

Histologically Confirmed Diagnostic Efficacy of F-rhPSMA-7 PET for N-Staging of Patients with Primary High-Risk Prostate Cancer.

J Nucl Med 2020 05 13;61(5):710-715. Epub 2019 Dec 13.

Department of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

F-rhPSMA-7 (radiohybrid prostate-specific membrane antigen [PSMA]) is a novel ligand for PET imaging. Here, we present data from a retrospective analysis using PET/CT and PET/MRI examinations to investigate the efficacy of F-rhPSMA-7 PET for primary N-staging of patients with prostate cancer (PC) compared with morphologic imaging (CT or MRI) and validated by histopathology. Data from 58 patients with high-risk PC (according to the D'Amico criteria) who were staged with F-rhPSMA-7 PET/CT or PET/MRI at our institution between July 2017 and June 2018 were reviewed. The patients had a median prescan prostate-specific antigen value of 12.2 ng/mL (range, 1.2-81.6 ng/mL). The median injected activity of F-rhPSMA-7 was 327 MBq (range, 132-410 MBq), with a median uptake time of 79.5 min (range, 60-153 min). All patients underwent subsequent radical prostatectomy and extended pelvic lymph node dissection. The presence of lymph node metastases was determined by an experienced reader independently for both the PET and the morphologic datasets using a template-based analysis on a 5-point scale. Patient-level and template-based results were both compared with histopathologic findings. Lymph node metastases were present in 18 patients (31.0%) and were located in 52 of 375 templates (13.9%). Receiver-operating-characteristic analyses showed F-rhPSMA-7 PET to perform significantly better than morphologic imaging on both patient-based and template-based analyses (areas under curve, 0.858 vs. 0.649 [ = 0.012] and 0.765 vs. 0.589 [ < 0.001], respectively). On patient-based analyses, the sensitivity, specificity, and accuracy of F-rhPSMA-7 PET were 72.2%, 92.5%, and 86.2%, respectively, and those of morphologic imaging were 50.0%, 72.5%, and 65.5%, respectively. On template-based analyses, the sensitivity, specificity, and accuracy of F-rhPSMA-7 PET were 53.8%, 96.9%, and 90.9%, respectively, and those of morphologic imaging were 9.6%, 95.0%, and 83.2%, respectively. F-rhPSMA-7 PET is superior to morphologic imaging for N-staging of high-risk primary PC. The efficacy of F-rhPSMA-7 is similar to published data for Ga-PSMA-11.
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http://dx.doi.org/10.2967/jnumed.119.234906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198390PMC
May 2020

Prostate-Specific Membrane Antigen-Guided Surgery.

J Nucl Med 2020 01 15;61(1):6-12. Epub 2019 Nov 15.

Department of Urology, Antoni van Leeuwenhoek Hospital-The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Since its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)-ligand PET has demonstrated great potential. PSMA-ligand imaging is increasingly influencing therapeutic decision making, although its impact on patient outcomes still needs to be defined. One relatively new application, enabled through chemical and engineering efforts, is PSMA-guided surgery. This review highlights the potential of PSMA-guided surgery and discusses its implications in lymph node dissection in primary and recurrent prostate cancer.
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http://dx.doi.org/10.2967/jnumed.119.232330DOI Listing
January 2020