Publications by authors named "Peter Albers"

245 Publications

Late relapsing germ cell tumors with elevated tumor markers.

World J Urol 2021 Sep 13. Epub 2021 Sep 13.

Department of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.

Purpose: Late relapsing germ cell tumors (LR-GCT) are considered a rare distinct biologic entity as their clinical presentation and response to treatment is different to early recurrences. While serum tumor markers (AFP and ß-HCG) play an important role at the time of first diagnosis to correctly classify prognosis and treatment of germ cell tumors, they may not have the same significance in a late relapse situation.

Patients And Methods: Thirty-seven patients with LR-GCT with elevated serum tumor markers were identified in our database. Twenty-six patients underwent primary surgical resection of the late relapsing tumor. Eleven patients received salvage chemotherapy and a post-chemotherapy residual tumor resection. Serum tumor markers, histological findings and oncological outcome were analyzed.

Results: In the histopathological specimen, viable cancer was found in 20 cases (54%) and teratoma was found in 16 cases (43%). In nine cases (24%), a somatic-type malignant transformation was present. In 19 of 37 patients (51.4%), the late relapse specimen presented a histological type of GCT, which was not present in the primary histology. Twenty-two patients (59.5%) were included in follow-up analysis. Mean and median follow-up time was 62.2 and 53 months, respectively. Seventeen patients (77.3%) suffered a relapse or had progressive disease after LR therapy. Five patients (22.7%) have been relapse-free after LR therapy (mean FU 61.6 months). Ten patients died of disease during follow-up (45.5%) and had a mean time from LR to death of 66.4 months. Eleven patients were alive at last follow-up (mean FU 62.2 months). Relapse and survival rate were similar between patients who received primary resection of LR tumor and patients who received salvage chemotherapy followed by surgery.

Conclusion: Patients with a late relapsing germ cell tumor and elevated markers have a poor prognosis and a high risk for another relapse independent on primary treatment. The histological type and aggressiveness of a late relapsing tumor cannot be predicted with serum tumor marker levels at the time of diagnosis of LR. In up to 54% of cases, primary histology did not coincide with LR histology. Therefore, we propose primary surgical resection of a late relapsing tumor if a complete resection is feasible in order to gain exact histology and tailor further treatment.
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http://dx.doi.org/10.1007/s00345-021-03833-zDOI Listing
September 2021

Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection - A 13-year follow-up analysis of a phase III trial cohort.

Eur J Cancer 2021 Sep 6;155:64-72. Epub 2021 Aug 6.

Department of Urology, Medical Faculty, University of Duesseldorf, Germany.

Background: One cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up.

Methods: Questionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND + two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75).

Results: With a median follow-up of 13.8 years (0-22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96-100%)/92% (CI 89-99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87-97%)/93% (CI 86-97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01).

Conclusions: With long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities.
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http://dx.doi.org/10.1016/j.ejca.2021.06.022DOI Listing
September 2021

A European Model for an Organised Risk-stratified Early Detection Programme for Prostate Cancer.

Eur Urol Oncol 2021 Aug 4. Epub 2021 Aug 4.

Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Context: Overdiagnosis as the argument to stop prostate cancer (PCa) screening is less valid since the introduction of new technologies such as risk calculators (RCs) and magnetic resonance imaging (MRI). These new technologies result in fewer unnecessary biopsy procedures and fewer cases of both overdiagnosis and underdetection. Therefore, we can now adequately respond to the growing and urgent need for a structured risk assessment to detect PCa early.

Objective: To provide expert discussion on the existing evidence for a previously published risk-stratified strategy regarding an organised population-based early detection programme for PCa.

Evidence Acquisition: The proposed algorithm for early detection of PCa emerged from expert consensus by the authors based on available evidence derived from a nonsystematic review of the current literature using Medline/PubMed, Cochrane Library database, ClinicalTrials.gov, ISRCTN Registry, and the European Association of Urology guidelines on PCa.

Evidence Synthesis: Although not confirmed by the highest level of evidence, current literature and guidelines point towards an algorithm for early detection of PCa that starts with risk-based prostate-specific antigen (PSA) testing, followed by multivariable risk stratification with RCs. All men who are classified to be at intermediate and high risk are then offered prostate MRI. The combined data from RCs and MRI results can be used to select men for prostate biopsy. Low-risk men return to a risk-based safety net that includes individualised PSA-interval tests and, if necessary, repeated MRI. Depending on local availability, the use of the different risk stratification tools may be adapted.

Conclusions: We present a risk-stratified algorithm for an organised population-based early detection programme for clinically significant PCa. Although the proposed strategy has not yet been analysed prospectively, it exploits and may even improve the most important available benefits of "PSA-only" screening studies, while at the same time reduces unnecessary biopsies and overdiagnosis by using new risk stratification tools.

Patient Summary: This paper presents a personalised strategy that enables selective early detection of prostate cancer by combining prostate-specific antigen (interval) testing' prediction models (risk calculators), and magnetic resonance imaging scans. This will likely lead to reduced prostate cancer-related morbidity and mortality, while reducing the need for prostate biopsy and limiting overdiagnosis.
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http://dx.doi.org/10.1016/j.euo.2021.06.006DOI Listing
August 2021

The developmental origin of cancers defines basic principles of cisplatin resistance.

Cancer Lett 2021 Oct 25;519:199-210. Epub 2021 Jul 25.

Department of Urology, Urological Research Laboratory, Translational UroOncology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany. Electronic address:

Cisplatin-based chemotherapy has been used for more than four decades as a standard therapeutic option in several tumor entities. However, being a multifaceted and heterogeneous phenomenon, inherent or acquired resistance to cisplatin remains a major obstacle during the treatment of several solid malignancies and inevitably results in disease progression. Hence, we felt there was an urgent need to evaluate common mechanisms between multifarious cancer entities to identify patient-specific therapeutic strategies. We found joint molecular and (epi)genetic resistance mechanisms and specific cisplatin-induced mutational signatures that depended on the developmental origin (endo-, meso-, ectoderm) of the tumor tissue. Based on the findings of thirteen tumor entities, we identified three resistance groups, where Group 1 (endodermal origin) prominently indicates NRF2-pathway activation, Group 2 (mesodermal origin, primordial germ cells) shares elevated DNA repair mechanisms and decreased apoptosis induction, and Group 3 (ectodermal and paraxial mesodermal origin) commonly presents deregulated apoptosis induction and alternating pathways as the main cisplatin-induced resistance mechanisms. This review further proposes potential and novel therapeutic strategies to improve the outcome of cisplatin-based chemotherapy.
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http://dx.doi.org/10.1016/j.canlet.2021.07.037DOI Listing
October 2021

The signal transducer CD24 suppresses the germ cell program and promotes an ectodermal rather than mesodermal cell fate in embryonal carcinomas.

Mol Oncol 2021 Jul 22. Epub 2021 Jul 22.

Department of Urology, Urological Research Laboratory, Translational UroOncology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany.

Testicular germ cell tumors (GCTs) are stratified into seminomas and nonseminomas. Seminomas share many histological and molecular features with primordial germ cells, whereas the nonseminoma stem cell population-embryonal carcinoma (EC)-is pluripotent and thus able to differentiate into cells of all three germ layers (teratomas). Furthermore, ECs are capable of differentiating into extra-embryonic lineages (yolk sac tumors, choriocarcinomas). In this study, we deciphered the molecular and (epi)genetic mechanisms regulating expression of CD24, a highly glycosylated signaling molecule upregulated in many cancers. CD24 is overexpressed in ECs compared with other GCT entities and can be associated with an undifferentiated pluripotent cell fate. We demonstrate that CD24 can be transactivated by the pluripotency factor SOX2, which binds in proximity to the CD24 promoter. In GCTs, CD24 expression is controlled by epigenetic mechanisms, that is, histone acetylation, since CD24 can be induced by the application histone deacetylase inhibitors. Vice versa, CD24 expression is downregulated upon inhibition of histone methyltransferases, E3 ubiquitin ligases, or bromodomain (BRD) proteins. Additionally, three-dimensional (3D) co-cultivation of EC cells with microenvironmental cells, such as fibroblasts, and endothelial or immune cells, reduced CD24 expression, suggesting that crosstalk with the somatic microenvironment influences CD24 expression. In a CRISPR/Cas9 deficiency model, we demonstrate that CD24 fulfills a bivalent role in differentiation via regulation of homeobox, and phospho- and glycoproteins; that is, it is involved in suppressing the germ cell/spermatogenesis program and mesodermal/endodermal differentiation, while poising the cells for ectodermal differentiation. Finally, blocking CD24 by a monoclonal antibody enhanced sensitivity toward cisplatin in EC cells, including cisplatin-resistant subclones, highlighting CD24 as a putative target in combination with cisplatin.
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http://dx.doi.org/10.1002/1878-0261.13066DOI Listing
July 2021

Addressing Equality of Representation in Urology Societies.

Eur Urol 2021 Oct 16;80(4):454-455. Epub 2021 Jul 16.

Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

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http://dx.doi.org/10.1016/j.eururo.2021.07.001DOI Listing
October 2021

Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy.

Eur Urol Oncol 2021 Jun 24. Epub 2021 Jun 24.

USC Institute of Urology, University of Southern California, Los Angeles, CA, USA.

Background: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown.

Objective: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy.

Design, Setting, And Participants: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016.

Outcome Measurements And Statistical Analysis: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM.

Results And Limitations: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%.

Conclusions: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials.

Patient Summary: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.
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http://dx.doi.org/10.1016/j.euo.2021.06.003DOI Listing
June 2021

ctDNA guiding adjuvant immunotherapy in urothelial carcinoma.

Nature 2021 07 16;595(7867):432-437. Epub 2021 Jun 16.

Roche/Genentech, South San Francisco, CA, USA.

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer. This trial did not reach its efficacy end point in the intention-to-treat population. Here we show that ctDNA testing at the start of therapy (cycle 1 day 1) identified 214 (37%) patients who were positive for ctDNA and who had poor prognosis (observation arm hazard ratio = 6.3 (95% confidence interval: 4.45-8.92); P < 0.0001). Notably, patients who were positive for ctDNA had improved disease-free survival and overall survival in the atezolizumab arm versus the observation arm (disease-free survival hazard ratio = 0.58 (95% confidence interval: 0.43-0.79); P = 0.0024, overall survival hazard ratio = 0.59 (95% confidence interval: 0.41-0.86)). No difference in disease-free survival or overall survival between treatment arms was noted for patients who were negative for ctDNA. The rate of ctDNA clearance at week 6 was higher in the atezolizumab arm (18%) than in the observation arm (4%) (P = 0.0204). Transcriptomic analysis of tumours from patients who were positive for ctDNA revealed higher expression levels of cell-cycle and keratin genes. For patients who were positive for ctDNA and who were treated with atezolizumab, non-relapse was associated with immune response signatures and basal-squamous gene features, whereas relapse was associated with angiogenesis and fibroblast TGFβ signatures. These data suggest that adjuvant atezolizumab may be associated with improved outcomes compared with observation in patients who are positive for ctDNA and who are at a high risk of relapse. These findings, if validated in other settings, would shift approaches to postoperative cancer care.
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http://dx.doi.org/10.1038/s41586-021-03642-9DOI Listing
July 2021

Surgical treatment of metastatic germ cell cancer.

Asian J Urol 2021 Apr 1;8(2):155-160. Epub 2020 Jun 1.

Department of Urology, University of Duesseldorf, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.

Among young men between the ages of 15 and 40 years, germ cell cancer is the most common solid tumor [1]. The worldwide incidence of germ cell cancer is 70 000 cases. Compared to all solid tumors of men, germ cell cancer accounts for 1% of all male tumors. Nevertheless, the mortality of this rare tumor entity is about 13% since 9507 patients died worldwide of germ cell cancer. The improvement in survival of germ cell cancer patients is due to a multimodal treatment of germ cell cancer including cisplatin-based chemotherapy and surgery leading to higher cure-rates even in advanced stages [1], whereas the increasing incidence of germ cell cancers cannot be thoroughly explained. In this article we review the current indications for surgery in metastatic germ cell cancers, highlight the strength and weaknesses of techniques and indications and raise the question how to improve surgical treatment in metastatic germ cell cancer.
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http://dx.doi.org/10.1016/j.ajur.2020.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099653PMC
April 2021

Molecular and epigenetic pathogenesis of germ cell tumors.

Asian J Urol 2021 Apr 30;8(2):144-154. Epub 2020 May 30.

Department of Urology, Urological Research Lab, Translational UroOncology, University Hospital Düsseldorf, Düsseldorf, Germany.

The development of germ cell tumors (GCTs) is a unique pathogenesis occurring at an early developmental stage during specification, migration or colonization of primordial germ cells (PGCs) in the genital ridge. Since driver mutations could not be identified so far, the involvement of the epigenetic machinery during the pathogenesis seems to play a crucial role. Currently, it is investigated whether epigenetic modifications occurring between the omnipotent two-cell stage and the pluripotent implanting PGCs might result in disturbances eventually leading to GCTs. Although progress in understanding epigenetic mechanisms during PGC development is ongoing, little is known about the complete picture of its involvement during GCT development and eventual classification into clinical subtypes. This review will shed light into the current knowledge of the complex epigenetic and molecular contribution during pathogenesis of GCTs by emphasizing on early developmental stages until arrival of late PGCs in the gonads. We questioned how misguided migrating and/or colonizing PGCs develop to either type I or type II GCTs. Additionally, we asked how pluripotency can be regulated during PGC development and which epigenetic changes contribute to GCT pathogenesis. We propose that SOX2 and SOX17 determine either embryonic stem cell-like (embryonal carcinoma) or PGC-like cell fate (seminoma). Finally, we suggest that factors secreted by the microenvironment, BMPs and BMP inhibiting molecules, dictate the fate decision of germ cell neoplasia (into seminoma and embryonal carcinoma) and seminomas (into embryonal carcinoma or extraembryonic lineage), indicating an important role of the microenvironment on GCT plasticity.
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http://dx.doi.org/10.1016/j.ajur.2020.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099689PMC
April 2021

Testicular germ cell tumors.

Authors:
Peter Albers

Asian J Urol 2021 Apr 19;8(2):143. Epub 2021 Feb 19.

Düsseldorf University Hospital, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany.

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http://dx.doi.org/10.1016/j.ajur.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099680PMC
April 2021

[Prostate cancer screening 2021 : Individualization, informed decision-making and additional diagnostic options are good for the disease and those affected].

Urologe A 2021 05 6;60(5):565-566. Epub 2021 May 6.

Klinik für Urologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.

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http://dx.doi.org/10.1007/s00120-021-01499-4DOI Listing
May 2021

Virtual Conferences and the COVID-19 Pandemic: Are We Missing Out with an Online Only Platform?

Eur Urol 2021 08 29;80(2):127-128. Epub 2021 Mar 29.

Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA; Georgia Cancer Center, Augusta, GA, USA. Electronic address:

Virtual conferences rapidly became the norm during the COVID-19 pandemic. Although necessary, there are shortfalls to strictly virtual meetings, including less enthusiasm for submitting abstracts. An approach that combines in-person attendance and virtual platforms may be an optimal compromise both during the ongoing pandemic and moving forward.
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http://dx.doi.org/10.1016/j.eururo.2021.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006189PMC
August 2021

Recommendations to Balance Benefits and Risks Of Thromboprophylaxis and to Avoid Central Venous-access Devices During First-line Chemotherapy in Men with Metastatic Germ Cell Tumors: The European Association Of Urology Testicular Cancer Panel Position in 2021.

Eur Urol 2021 Jul 12;80(1):4-6. Epub 2021 Mar 12.

Department of Urology Medipol Mega, Istanbul Medipol University, Istanbul, Turkey.

Men with metastatic germ cell tumors undergoing chemotherapy are at high risk of venous thromboembolic events and low risk of bleeding. A central venous-access device should be avoided whenever possible. Thromboprophylaxis may be prescribed after balancing the risks and benefits for each individual patient.
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http://dx.doi.org/10.1016/j.eururo.2021.02.032DOI Listing
July 2021

Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial.

Lancet Oncol 2021 04 12;22(4):525-537. Epub 2021 Mar 12.

Barts Cancer Institute, Queen Mary University of London, St Bartholomew's Hospital, London, UK.

Background: Despite standard curative-intent treatment with neoadjuvant cisplatin-based chemotherapy, followed by radical surgery in eligible patients, muscle-invasive urothelial carcinoma has a high recurrence rate and no level 1 evidence for adjuvant therapy. We aimed to evaluate atezolizumab as adjuvant therapy in patients with high-risk muscle-invasive urothelial carcinoma.

Method: In the IMvigor010 study, a multicentre, open-label, randomised, phase 3 trial done in 192 hospitals, academic centres, and community oncology practices across 24 countries or regions, patients aged 18 years and older with histologically confirmed muscle-invasive urothelial carcinoma and an Eastern Cooperative Oncology Group performance status of 0, 1, or 2 were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection. Patients had ypT2-4a or ypN+ tumours following neoadjuvant chemotherapy or pT3-4a or pN+ tumours if no neoadjuvant chemotherapy was received. Patients not treated with neoadjuvant chemotherapy must have been ineligible for or declined cisplatin-based adjuvant chemotherapy. No post-surgical radiotherapy or previous adjuvant chemotherapy was allowed. Patients were randomly assigned (1:1) using a permuted block (block size of four) method and interactive voice-web response system to receive 1200 mg atezolizumab given intravenously every 3 weeks for 16 cycles or up to 1 year, whichever occurred first, or to observation. Randomisation was stratified by previous neoadjuvant chemotherapy use, number of lymph nodes resected, pathological nodal status, tumour stage, and PD-L1 expression on tumour-infiltrating immune cells. The primary endpoint was disease-free survival in the intention-to-treat population. Safety was assessed in patients who either received at least one dose of atezolizumab or had at least one post-baseline safety assessment. This trial is registered with ClinicalTrials.gov, NCT02450331, and is ongoing but not recruiting patients.

Findings: Between Oct 5, 2015, and July 30, 2018, we enrolled 809 patients, of whom 406 were assigned to the atezolizumab group and 403 were assigned to the observation group. Median follow-up was 21·9 months (IQR 13·2-29·8). Median disease-free survival was 19·4 months (95% CI 15·9-24·8) with atezolizumab and 16·6 months (11·2-24·8) with observation (stratified hazard ratio 0·89 [95% CI 0·74-1·08]; p=0·24). The most common grade 3 or 4 adverse events were urinary tract infection (31 [8%] of 390 patients in the atezolizumab group vs 20 [5%] of 397 patients in the observation group), pyelonephritis (12 [3%]) vs 14 [4%]), and anaemia (eight [2%] vs seven [2%]). Serious adverse events occurred in 122 (31%) patients who received atezolizumab and 71 (18%) who underwent observation. 63 (16%) patients who received atezolizumab had a treatment-related grade 3 or 4 adverse event. One treatment-related death, due to acute respiratory distress syndrome, occurred in the atezolizumab group.

Interpretation: To our knowledge, IMvigor010 is the largest, first-completed phase 3 adjuvant study to evaluate the role of a checkpoint inhibitor in muscle-invasive urothelial carcinoma. The trial did not meet its primary endpoint of improved disease-free survival in the atezolizumab group over observation. Atezolizumab was generally tolerable, with no new safety signals; however, higher frequencies of adverse events leading to discontinuation were reported than in metastatic urothelial carcinoma studies. These data do not support the use of adjuvant checkpoint inhibitor therapy in the setting evaluated in IMvigor010 at this time.

Funding: F Hoffmann-La Roche/Genentech.
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http://dx.doi.org/10.1016/S1470-2045(21)00004-8DOI Listing
April 2021

Robotic-assisted Versus Laparoscopic Surgery: Outcomes from the First Multicentre, Randomised, Patient-blinded Controlled Trial in Radical Prostatectomy (LAP-01).

Eur Urol 2021 Jun 9;79(6):750-759. Epub 2021 Feb 9.

Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany; Institute for Medical Informatics, Statistics and Epidemiology University of Leipzig, Leipzig, Germany.

Background: The LAP-01 trial was designed to address the lack of high-quality literature comparing robotic-assisted (RARP) and laparoscopic (LRP) radical prostatectomy.

Objective: To compare the functional and oncological outcomes between RARP and LRP at 3 mo of follow-up.

Design, Setting, And Participants: In this multicentre, randomised, patient-blinded controlled trial, patients referred for radical prostatectomy to four hospitals in Germany were randomly assigned (3:1) to undergo either RARP or LRP.

Outcome Measurements And Statistical Analysis: The primary outcome was time to continence recovery at 3 mo based on the patient's pad diary. Secondary outcomes included continence and potency as well as quality of life in addition to oncological outcomes for up to 3 yr of follow-up. Time to continence was analysed by log-rank test and depicted by the Kaplan-Meier method. Continuous measurements were analysed by means of linear mixed models.

Results And Limitations: A total of 782 patients were randomised. The primary endpoint was evaluable in 718 patients (547 RARPs; full analysis set). At 3 mo, the difference in continence rates was 8.7% in favour of RARP (54% vs 46%, p =  0.027). RARP remained superior to LRP even after adjustment for the randomisation stratum nerve sparing and age >65 yr (hazard ratio = 1.40 [1.09-1.81], p =  0.008). A significant benefit in early potency recovery was also identified, while similar oncological and morbidity outcomes were documented. It is a limitation that the influence of different anastomotic techniques was not investigated in this study.

Conclusions: RARP resulted in significantly better continence recovery at 3 mo.

Patient Summary: In this randomised trial, we looked at the outcomes following radical prostate surgery in a large German population. We conclude that patients undergoing robotic prostatectomy had better continence than those undergoing laparoscopic surgery when assessed at 3 mo following surgery. Age and the nerve-sparing technique further affected continence restoration.
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http://dx.doi.org/10.1016/j.eururo.2021.01.030DOI Listing
June 2021

Solving problems is smart, preventing them is wise: Lessons learned from the 2nd International DKFZ Conference on Cancer Prevention.

Int J Cancer 2021 06 27;148(12):3086-3096. Epub 2021 Feb 27.

German Cancer Research Center (DKFZ), Heidelberg, Germany.

The 2nd International DKFZ Conference on Cancer Prevention (CCP2020) organized by the German Cancer Research Center (DKFZ) was held as a virtual event on 17-18 September 2020. The event gathered experts on cancer prevention from around the world with the aim of generating a stimulating interchange of opinions between clinicians and basic researchers working in the field. The talks and posters of the conference fueled exciting discussions and debates about the state of the art of cancer prevention and provided a comprehensive outlook on the many aspects of the field. The program was divided into three main sessions, illustrating the most recent methodological approaches and interventions in primary, secondary and tertiary prevention, enriched by introductory lectures depicting the most relevant aspects of each session. The key concepts covered in this meeting were risk factors, early detection, improving life after cancer, cancer prevention in Europe and personalized prevention. The importance of the latter was expressly highlighted, many presentations emphasizing that in the era of personalized medicine, prevention also needs to be based on the unique genetic, epigenetic, social and behavioral characteristics of the individual to achieve maximal efficacy. In this article, we summarize the key messages emerging from each section, with particular attention on the most important challenges yet to be met in the field of cancer prevention.
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http://dx.doi.org/10.1002/ijc.33502DOI Listing
June 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 Jun 2;60(3):216-223. 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
June 2021

Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.

Urol Int 2021 22;105(3-4):181-191. Epub 2021 Jan 22.

II. Medical Clinic and Polyclinic, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Objectives: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects.

Materials And Methods: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements.

Results: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy.

Conclusion: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.
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http://dx.doi.org/10.1159/000511245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006578PMC
July 2021

The pioneer and differentiation factor FOXA2 is a key driver of yolk-sac tumour formation and a new biomarker for paediatric and adult yolk-sac tumours.

J Cell Mol Med 2021 02 14;25(3):1394-1405. Epub 2021 Jan 14.

Department of Urology, Urological Research Lab, Translational UroOncology, University Hospital Düsseldorf, Düsseldorf, Germany.

Yolk-sac tumours (YSTs), a germ cell tumour subtype, occur in newborns and infants as well as in young adults of age 14-44 years. In clinics, adult patients with YSTs face a poor prognosis, as these tumours are often therapy-resistant and count for many germ cell tumour related deaths. So far, the molecular and (epi)genetic mechanisms that control development of YST are far from being understood. We deciphered the molecular and (epi)genetic mechanisms regulating YST formation by meta-analysing high-throughput data of gene and microRNA expression, DNA methylation and mutational burden. We validated our findings by qRT-PCR and immunohistochemical analyses of paediatric and adult YSTs. On a molecular level, paediatric and adult YSTs were nearly indistinguishable, but were considerably different from embryonal carcinomas, the stem cell precursor of YSTs. We identified FOXA2 as a putative key driver of YST formation, subsequently inducing AFP, GPC3, APOA1/APOB, ALB and GATA3/4/6 expression. In YSTs, WNT-, BMP- and MAPK signalling-related genes were up-regulated, while pluripotency- and (primordial) germ cell-associated genes were down-regulated. Expression of FOXA2 and related key factors seems to be regulated by DNA methylation, histone methylation / acetylation and microRNAs. Additionally, our results highlight FOXA2 as a promising new biomarker for paediatric and adult YSTs.
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http://dx.doi.org/10.1111/jcmm.16222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875904PMC
February 2021

Structure and spectroscopy of methionyl-methionine for aquaculture.

Sci Rep 2021 01 11;11(1):458. Epub 2021 Jan 11.

Evonik Operations GmbH, Rodenbacher Chaussee 4, 63457, Hanau-Wolfgang, Germany.

The amino acid L-methionine is an essential amino acid and is commonly used as a feed supplement in terrestrial animals. It is less suitable for marine organisms because it is readily excreted. It is also highly water soluble and this results in loss of the feed and eutrophication of the water. To address these problems, the dipeptide DL-methionyl-DL-methionine (trade name: AQUAVI Met-Met) has been developed as a dedicated methionine source for aquaculture. The commercial product is a mixture of a racemic crystal form of D-methionyl-D-methionine/L-methionyl-L-methionine and a racemic crystal form of D-methionyl-L-methionine/L-methionyl-D-methionine. In this work, we have computationally, structurally, spectroscopically and by electron microscopy characterised these materials. The microscopy and spectroscopy demonstrate that there is no interaction between the DD-LL and DL-LD racemates on any length scale from the macroscopic to the nanoscale.
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http://dx.doi.org/10.1038/s41598-020-80385-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801548PMC
January 2021

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

Urol Int 2021 7;105(3-4):169-180. Epub 2021 Jan 7.

II. Medical Clinic and Polyclinic, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Introduction: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages.

Methods: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements.

Results: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma.

Conclusion: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.
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http://dx.doi.org/10.1159/000510407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006579PMC
July 2021

Early Detection of Prostate Cancer in 2020 and Beyond: Facts and Recommendations for the European Union and the European Commission.

Eur Urol 2021 03 29;79(3):327-329. Epub 2020 Dec 29.

Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.

The burden of prostate cancer is increasing. Therefore, we need to implement a contemporary, organized, risk-stratified program for early detection to reduce both the harm from the disease and potential overdiagnosis and overtreatment, while avoiding underdiagnosis to considerably improve the harm-to-benefit ratio.
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http://dx.doi.org/10.1016/j.eururo.2020.12.010DOI Listing
March 2021

Equivocal PI-RADS Three Lesions on Prostate Magnetic Resonance Imaging: Risk Stratification Strategies to Avoid MRI-Targeted Biopsies.

J Pers Med 2020 Dec 10;10(4). Epub 2020 Dec 10.

Department of Urology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.

We aimed to investigate the relation between largest lesion diameter, prostate-specific antigen density (PSA-D), age, and the detection of clinically significant prostate cancer (csPCa) using first-time targeted biopsy (TBx) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3 index lesions. A total of 292 men (2013-2019) from two referral centers were included. A multivariable logistic regression analysis was performed. The discrimination and clinical utility of the built model was assessed by the area under the receiver operation curve (AUC) and decision curve analysis, respectively. A higher PSA-D and higher age were significantly related to a higher risk of detecting csPCa, while the largest index lesion diameter was not. The discrimination of the model was 0.80 (95% CI 0.73-0.87). When compared to a biopsy-all strategy, decision curve analysis showed a higher net benefit at threshold probabilities of ≥2%. Accepting a missing ≤5% of csPCa diagnoses, a risk-based approach would result in 34% of TBx sessions and 23% of low-risk PCa diagnoses being avoided. In men with PI-RADS 3 index lesions scheduled for first-time TBx, the balance between the number of TBx sessions, the detection of low-risk PCa, and the detection of csPCa does not warrant a biopsy-all strategy. To minimize the risk of missing the diagnosis of csPCa but acknowledging the need of avoiding unnecessary TBx sessions and overdiagnosis, a risk-based approach is advisable.
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http://dx.doi.org/10.3390/jpm10040270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768373PMC
December 2020

Re: The 111 Study: A Single-arm, Phase 3 Trial Evaluating One Cycle of Bleomycin, Etoposide, and Cisplatin as Adjuvant Chemotherapy in High-risk, Stage 1 Nonseminomatous or Combined Germ Cell Tumours of the Testis.

Authors:
Peter Albers

Eur Urol 2021 01 20;79(1):160-161. Epub 2020 Nov 20.

Professor of Urology and Chair, Department of Urology, University Hospital, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2020.08.010DOI Listing
January 2021

Short-term and long-term outcomes after resection of thoracic growing teratoma syndrome.

World J Urol 2021 Jul 31;39(7):2579-2585. Epub 2020 Oct 31.

Department of Thoracic Surgery, Agaplesion Markus Krankenhaus Frankfurt, Wilhelm-Epstein-Str. 4, 60431, Frankfurt, Germany.

Purpose: Thoracic growing teratoma syndrome (TGTS) is a rare disease in patients with germ cell tumors. Other than a few case reports and a limited number of case series, studies of this topic are not available.

Methods: We retrospectively analyzed the data from our patients who received surgery for TGTS between 1999 and 2016. Descriptive statistical analyses were performed to analyze the characteristics of the patients, tumors, and short-term outcomes. Furthermore, the long-term outcomes and survival curves were analyzed using the Kaplan-Meier method.

Results: Twenty-nine patients underwent surgery for TGTS. The median age was 32 years (range: 19-50 years). All patients received cisplatin-based chemotherapy. Many of the patients had multilocalized TGTS (n = 10). The median tumor size was 64.5 mm (range 10-210 mm). In all cases, R0 resection was achieved. The minor morbidity, major morbidity, and mortality rates were 3.4%, 6.9%, and 0%, respectively. Altogether, 28 patients were included in the long-term follow-up analysis, with a median follow-up time of 94 months (13-237 months). The 5-, 10-, and 15-year survival rates were 93%, 93%, and 84%, respectively.

Conclusions: TGTS may occur in multiple localizations and grow to a large tumor size. The resection of TGTS can be performed with low morbidity and mortality rates and is associated with good overall survival after complete resection. Important are an early detection and knowledge of the systemic treatment options by the oncologist and urologist, as well as a thoracic surgeon with a large experience in extended thoracic resections.
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http://dx.doi.org/10.1007/s00345-020-03503-6DOI Listing
July 2021

Investigation of Commercial Graphenes.

ChemistryOpen 2020 10 19;9(10):1060-1064. Epub 2020 Oct 19.

Evonik Technology & Infrastructure GmbH 915 D115, Rodenbacher Chaussee 4, 63457, Hanau-Wolfgang, Germany.

For graphene to achieve its full scientific and commercial potential, reliable mass production of the material on the multi-tonne scale is essential. We have investigated five samples of graphene obtained from commercial sources that state they can supply the product on the tonne scale per annum. From electron microscopy at the micrometre to the nanometre scale, and neutron vibrational spectroscopy, we find that none of the materials examined were 100 % isolated graphene sheets. In all cases, there was a substantial content of graphite-like material. The samples exhibited varying oxygen contents, this could be present as carboxylic acid (although other oxygenates, quinones, phenols may also be present) or water. We emphasise that INS spectroscopy is particularly useful for the investigation of inorganic materials that will be used commercially: it provides atomic scale information from macroscopic (10's of g) amounts of sample, thus ensuring that the results are truly representative.
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http://dx.doi.org/10.1002/open.202000234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569895PMC
October 2020
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