Physiological aging and inflammation-induced cellular senescence may contribute to oligodendroglial dysfunction in MS.

Aging affects all cell types in the CNS and plays an important role in CNS diseases. However, the underlying molecular mechanisms driving these age-associated changes and their contribution to diseases are only poorly understood. The white matter in the aging brain as well as in diseases, such as Multiple sclerosis is characterized by subtle abnormalities in myelin sheaths and paranodes, suggesting that oligodendrocytes, the myelin-maintaining cells of the CNS, lose the capacity to preserve a proper myelin structure and potentially function in age and certain diseases. Here, we made use of directly converted oligodendrocytes (dchiOL) from young, adult and old human donors to study age-associated changes. dchiOL from all three age groups differentiated in an comparable manner into O4 + immature oligodendrocytes, but the proportion of MBP + mature dchiOL decreased with increasing donor age. This was associated with an increased ROS production and upregulation of cellular senescence markers such as CDKN1A, CDKN2A in old dchiOL. Comparison of the transcriptomic profiles of dchiOL from adult and old donors revealed 1324 differentially regulated genes with limited overlap with transcriptomic profiles of the donors' fibroblasts or published data sets from directly converted human neurons or primary rodent oligodendroglial lineage cells. Methylome analyses of dchiOL and human white matter tissue samples demonstrate that chronological and epigenetic age correlate in CNS white matter as well as in dchiOL and resulted in the identification of an age-specific epigenetic signature. Furthermore, we observed an accelerated epigenetic aging of the myelinated, normal appearing white matter of multiple sclerosis (MS) patients compared to healthy individuals. Impaired differentiation and upregulation of cellular senescence markers could be induced in young dchiOL in vitro using supernatants from pro-inflammatory microglia. In summary, our data suggest that physiological aging as well as inflammation-induced cellular senescence contribute to oligodendroglial pathology in inflammatory demyelinating diseases such as MS.

Targeting the glutamine metabolism to suppress cell proliferation in mesenchymal docetaxel-resistant prostate cancer.

Docetaxel (DX) serves as a palliative treatment option for metastatic prostate cancer (PCa). Despite initial remission, acquired DX resistance is inevitable. The mechanisms behind DX resistance have not yet been deciphered, but a mesenchymal phenotype is associated with DX resistance. Mesenchymal phenotypes have been linked to metabolic rewiring, obtaining most ATP production by oxidative phosphorylation (OXPHOS) powered substantially by glutamine (Gln). Likewise, Gln is known to play an essential role in modulating bioenergetic, redox homeostasis and autophagy. Herein, investigations of Gln deprivation on DX-sensitive and -resistant (DR) PCa cells revealed that the DR cell sub-lines were susceptible to Gln deprivation. Mechanistically, Gln deprivation reduced OXPHOS and ATP levels, causing a disturbance in cell cycle progression. Genetic and chemical inhibition of the Gln-metabolism key protein GLS1 could validate the Gln deprivation results, thereby representing a valid therapeutic target. Moreover, immunohistological investigation of GLS1 revealed a high-expressing GLS1 subgroup post-docetaxel failure, exhibiting low overall survival. This subgroup presents an intriguing opportunity for targeted therapy focusing on glutamine metabolism. Thus, these findings highlight a possible clinical rationale for the chemical inhibition of GLS1 as a therapeutic strategy to target mesenchymal DR PCa cells, thereby delaying accelerated tumour progression.

Cell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment.

5q-associated spinal muscular atrophy (SMA) is a motoneuron disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Adaptive immunity may contribute to SMA as described in other motoneuron diseases, yet mechanisms remain elusive. Nusinersen, an antisense treatment, enhances SMN2 expression, benefiting SMA patients. Here we have longitudinally investigated SMA and nusinersen effects on local immune responses in the cerebrospinal fluid (CSF) - a surrogate of central nervous system parenchyma. Single-cell transcriptomics (SMA: N = 9 versus Control: N = 9) reveal NK cell and CD8+ T cell expansions in untreated SMA CSF, exhibiting activation and degranulation markers. Spatial transcriptomics coupled with multiplex immunohistochemistry elucidate cytotoxicity near chromatolytic motoneurons (N = 4). Post-nusinersen treatment, CSF shows unaltered protein/transcriptional profiles. These findings underscore cytotoxicity's role in SMA pathogenesis and propose it as a therapeutic target. Our study illuminates cell-mediated cytotoxicity as shared features across motoneuron diseases, suggesting broader implications.

[Structural health care reality in the surgical treatment of male stress incontinence in Germany]. / Strukturelle Versorgungssituation der operativen Therapie bei männlicher Belastungsinkontinenz in Deutschland.

BACKGROUND: Stress urinary incontinence in men is predominantly iatrogenic after radical prostatectomy or transurethral interventions. Current studies show that there is a deficit in the availability of surgical therapy not only in Germany. The aim of this study is to investigate in more detail the structural health care situation of surgical treatment of male stress incontinence in Germany. MATERIALS AND METHODS: The evaluation of the surgical therapy of male stress incontinence in Germany is based on the OPS (Operationen- und Prozedurenschlüssel-German procedural classification) codes from hospital quality reports from 2011-2019. RESULTS: From 2012-2019, the number of male incontinence surgeries declined from 2191 to 1445. The number of departments performing incontinence surgeries decreased from 275 to 244. In the multivariate analysis, a high number (≥ 50) of radical prostatectomies/year (RPE/year) is an independent predictor of a high-volume centre (≥ 10 procedures/year; odds ratio [OR] 6.4 [2.3-17.6]; p < 0.001). The most significant decrease was in sling surgery (from 1091 to 410; p < 0.001). Here, the number of cases decreased especially in departments that implanted a high number of slings (≥ 10 slings/year; -69%; -62.4 ± 15.5 surgeries/year; p = 0.007). In addition, the number of departments implanting slings decreased over the investigated time period (from 34 to 10; p < 0.001). This particularly affected departments that also had a low number of RPE/year (from 9 to 0; -100%). CONCLUSION: The situation of surgical treatment of male stress urinary incontinence in Germany shows a clear decline in sling implantation, especially in small departments. On the one hand, this reflects the increasingly differentiated indications for sling implantation. On the other hand, it raises the suspicion that a gap in care has developed, as the decline was not compensated for by other surgical therapies.

Identification of novel snoRNA-based biomarkers for clear cell renal cell carcinoma from urine-derived extracellular vesicles.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC with high rates of metastasis. Targeted therapies such as tyrosine kinase and checkpoint inhibitors have improved treatment success, but therapy-related side effects and tumor recurrence remain a challenge. As a result, ccRCC still have a high mortality rate. Early detection before metastasis has great potential to improve outcomes, but no suitable biomarker specific for ccRCC is available so far. Therefore, molecular biomarkers derived from body fluids have been investigated over the past decade. Among them, RNAs from urine-derived extracellular vesicles (EVs) are very promising. METHODS: RNA was extracted from urine-derived EVs from a cohort of 78 subjects (54 ccRCC patients, 24 urolithiasis controls). RNA-seq was performed on the discovery cohort, a subset of the whole cohort (47 ccRCC, 16 urolithiasis). Reads were then mapped to the genome, and expression was quantified based on 100 nt long contiguous genomic regions. Cluster analysis and differential region expression analysis were performed with adjustment for age and gender. The candidate biomarkers were validated by qPCR in the entire cohort. Receiver operating characteristic, area under the curve and odds ratios were used to evaluate the diagnostic potential of the models. RESULTS: An initial cluster analysis of RNA-seq expression data showed separation by the subjects' gender, but not by tumor status. Therefore, the following analyses were done, adjusting for gender and age. The regions differentially expressed between ccRCC and urolithiasis patients mainly overlapped with small nucleolar RNAs (snoRNAs). The differential expression of four snoRNAs (SNORD99, SNORD22, SNORD26, SNORA50C) was validated by quantitative PCR. Confounder-adjusted regression models were then used to classify the validation cohort into ccRCC and tumor-free subjects. Corresponding accuracies ranged from 0.654 to 0.744. Models combining multiple genes and the risk factors obesity and hypertension showed improved diagnostic performance with an accuracy of up to 0.811 for SNORD99 and SNORA50C (p = 0.0091). CONCLUSIONS: Our study uncovered four previously unrecognized snoRNA biomarkers from urine-derived EVs, advancing the search for a robust, easy-to-use ccRCC screening method.

EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics.

DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data. Given these diverse approaches to methylation profiling, to date, there is no single tool that allows (1) classification and interpretation of microarray, nanopore and parallel sequencing data, (2) direct control of nanopore sequencers, and (3) the integration of microarray-based methylation reference data. Furthermore, no software capable of entirely running in routine diagnostic laboratory environments lacking high-performance computing and network infrastructure exists. To overcome these shortcomings, we present EpiDiP/NanoDiP as an open-source DNA methylation and copy number profiling suite, which has been benchmarked against an established supervised machine learning approach using in-house routine diagnostics data obtained between 2019 and 2021. Running locally on portable, cost- and energy-saving system-on-chip as well as gpGPU-augmented edge computing devices, NanoDiP works in offline mode, ensuring data privacy. It does not require the rigid training data annotation of supervised approaches. Furthermore, NanoDiP is the core of our public, free-of-charge EpiDiP web service which enables comparative methylation data analysis against an extensive reference data collection. We envision this versatile platform as a useful resource not only for neuropathologists and surgical pathologists but also for the tumour epigenetics research community. In daily diagnostic routine, analysis of native, unfixed biopsies by NanoDiP delivers molecular tumour classification in an intraoperative time frame.

Retinal and choroidal efficacy of switching treatment to faricimab in recalcitrant neovascular age related macular degeneration.

Aim of this study was to evaluate the efficacy of switching treatment to faricimab in neovascular age-related macular degeneration (nAMD) from other anti-VEGF agents. Fifty-eight eyes of fifty-one patients with nAMD and a full upload series of four faricimab injections were included. Demographic data, multimodal imaging and treatment parameters were recorded. The primary outcome measures were changes in central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). A subgroup analysis was performed for eyes with prior ranibizumab (R) or aflibercept (A) treatment. Mean injection intervals before and after switching were comparable (33.8 ± 11.2 vs. 29.3 ± 2.6 days; p = 0.08). Mean CST of 361.4 ± 108.1 µm prior to switching decreased significantly to 318.3 ± 97.7 µm (p < 0.01) after the third faricimab injection, regardless of prior anti-VEGF treatment (p < 0.01). Although SFCT slightly improved for the whole cohort from 165.8 ± 76.8 µm to 161.0 ± 82,8 µm (p = 0.029), subgroup analysis did not confirm this positive effect (subgroup R: p = 0.604; subgroup A: p = 0.306). In patients with a suboptimal response to aflibercept or ranibizumab in nAMD, farcimab can improve CST and slightly improve or maintain SFCT. Further prospective randomized trials are warranted.

Multicenter evaluation of complex urinary diversion for renal transplantation: outcomes of complex surgical solutions.

PURPOSE: An abnormal lower urinary tract poses significant challenges for transplant surgeons. Besides the ureteral anastomosis to an ileal conduit, there are diverse complex reconstructive solutions. Due to its rarity, standardization and teaching of complex urinary diversion is extremely difficult. METHODS: The indications and outcomes of complex urinary diversions after kidney transplantation (KT) were retrospectively investigated at eight urologic transplant centers including a current follow-up. RESULTS: Of 37 patients with 21 (56%) males, vesicoureteral reflux (24%), spina bifida (22%), and glomerulonephritis (12%) were the most common causes of terminal renal failure. In 30 (81%) patients, urinary diversion was performed before KT, at a median of 107.5 (range, 10; 545) months before. Transplantations were held at a median patient age of 43 (10; 68) years, including six (16%) living donations. Urinary diversion was modified during 12 (32%) transplantations. After KT, the ileal conduit was the most common incontinent urinary diversion in 25 (67%) patients; a Mainz pouch I and bladder augmentation were the most frequent continent diversions (each n = 3). At a median follow-up of 120 months (range 0; 444), 12 (32%) patients had a graft failure with a 5-year graft survival of 79% (95%CI 61; 90). The median overall survival was 227 months (168; 286) and the 5-year overall survival 89% (69.3; 96.4). CONCLUSION: The mid-term kidney transplant function with complex urinary diversion appears to be comparable to transplants with regular urinary diversions. Hence, complex urinary diversion should always be considered as a surgical option, even during transplantation, if necessary.

Utilization of sperm cryopreservation in patients with testicular cancer.

PURPOSE: We assessed factors that affect the utilization of sperm cryopreservation before 2021, when patients covered expenses, and the influence on quality of life. METHODS: Between 2011 and 2021, testicular cancer survivors (TCS) at our clinic completed a questionnaire, including EORTC QLQ-TC26, covering sperm cryopreservation, sociodemographic details, post-treatment births, and artificial insemination. RESULTS: After 5.7 ± 3.0 years, 279 participants (64%) responded to the questionnaire. Among them, 33% (91/279) of testicular cancer survivors chose sperm cryopreservation prior to treatment, with 11% (10/91) using it for insemination. Conversely, 2% (3/188) without cryopreservation reported unfulfilled desire to have children. Univariate analysis showed TCS with cryopreservation were younger (30.6 ± 7.1 (35 (21-59)) vs. 42.4 ± 10.9 (48 (22-81)) years; p = 0.001), had a lower BMI (24.2 ± 3.3 vs. 26.6 ± 4.6 kg/m2; p = 0.009) and a lower Charlson Score (> 3: 36% vs. 60%; p < 0.001). Multivariate analysis revealed older age (≥ 37 years: OR 13.1 (5.5-31.2), p < 0.001) and lower education (middle school or less: OR 3.3 (1.6-6.9), p = 0.001) as independent factors associated with not undergoing cryopreservation. Regarding quality of life, multivariate analysis identified a lower infertility anxiety score (OR 4.3 (2.0-9.0), p < 0.001) and higher age (≥ 44 years: OR 5.4 (2.6-11.3); p < 0.001) as predictors for the absence of prior cryopreservation. CONCLUSIONS: Age and education seem to impact the choice of undergoing paid sperm cryopreservation. Urologists should inform testicular cancer patients about costs and coverage. Importantly, the occurrence of unmet desires for parenthood is minimal among those who forego cryopreservation.

Online decision aid for patients with prostate cancer evaluated by 11 290 patients and 91 urologists in Germany.

OBJECTIVE: To evaluate the nationwide online decision aid 'Entscheidungshilfe Prostatakrebs' (established in 2016, >11.000 users and 60 new users/week) for patients with non-metastatic prostate cancer (PCa), from the perspective of patients and urologists. PATIENTS AND METHODS: To provide personalised information, the tool collects most of the International Consortium for Health Outcomes Measurement standard set, personal preferences, psychological features, and a validated rating of the tool. To evaluate urologists' opinions, we developed a structured two-page questionnaire. All data were collected anonymously. RESULTS: From June 2016 to December 2020, 11 290 patients used the PCa decision aid. Their median (interquartile range [IQR]) age was 67 (61-72) years. The median (IQR) time from initial diagnosis to using the tool was 4 (3-7) weeks. In all, 87.7% of users reported high satisfaction. In a multivariable model, predictors for considering observation were higher knowledge, using the decision aid alone, lower oncological risk, normal erectile function, and respective personal preferences. Of 194 urologists, 91 (47%) had implemented the decision aid in their clinical practice. The urologists' mean (SD) satisfaction score (1 'very good'; 6 'unsatisfactory') with it was 1.45 (0.55), and 92% recommended it. Half of the urologists reported time savings. CONCLUSION: Patients and urologists report a very high level of acceptance and satisfaction with this online tool. It offers advantages in shared decision-making and time efficiency. The usage of the decision aid might improve the adoption of active surveillance and watchful waiting when indicated.

Genome-matched treatments and patient outcomes in the Maine Cancer Genomics Initiative (MCGI).

Genomic tumor testing (GTT) is an emerging technology aimed at identifying variants in tumors that can be targeted with genomically matched drugs. Due to limited resources, rural patients receiving care in community oncology settings may be less likely to benefit from GTT. We analyzed GTT results and observational clinical outcomes data from patients enrolled in the Maine Cancer Genomics Initiative (MCGI), which provided access to GTTs; clinician educational resources; and genomic tumor boards in community practices in a predominantly rural state. 1603 adult cancer patients completed enrollment; 1258 had at least one potentially actionable variant identified. 206 (16.4%) patients received a total of 240 genome matched treatments, of those treatments, 64% were FDA-approved in the tumor type, 27% FDA-approved in a different tumor type and 9% were given on a clinical trial. Using Inverse Probability of Treatment Weighting to adjust for baseline characteristics, a Cox proportional hazards model demonstrated that patients who received genome matched treatment were 31% less likely to die within 1 year compared to those who did not receive genome matched treatment (HR: 0.69; 95% CI: 0.52-0.90; p-value: 0.006). Overall, GTT through this initiative resulted in levels of genome matched treatment that were similar to other initiatives, however, clinical trials represented a smaller share of treatments than previously reported, and "off-label" treatments represented a greater share. Although this was an observational study, we found evidence for a potential 1-year survival benefit for patients who received genome matched treatments. These findings suggest that when disseminated and implemented with a supportive infrastructure, GTT may benefit cancer patients in rural community oncology settings, with further work remaining on providing genome-matched clinical trials.

PI-RADS upgrading as the strongest predictor for the presence of clinically significant prostate cancer in patients with initial PI-RADS-3 lesions.

PURPOSE: Unclear lesions on multiparametric magnetic resonance tomography (mpMRI) are challenging for the indication of biopsy in patients with clinical suspicion of prostate cancer (PCa). The aim of this study is the validation of the detection rate of clinically significant PCa (csPCa) in patients with PI-RADS 3 findings and to determine the appropriate follow-up strategy. METHODS: In this retrospective single-center study, patients with maximum PI-RADS 3 lesions underwent targeted MRI/ultrasound-fusion biopsy (tPbx) combined with systematic 12-core biopsy (sPbx) and follow-up mpMRI with further control biopsy. We assessed the evolution of MRI findings (PI-RADS, volume of the lesion), clinical parameters and histopathology in follow-up MRI and biopsies. The primary objective is the detection rate of csPCa, defined as ISUP ≥ 2 findings. RESULTS: A total of 126 patients (median PSA 6.65 ng/ml; median PSA-density (PSAD) 0.13 ng/ml2) were included. The initial biopsy identified low-risk PCa in 24 cases (19%). During follow-up biopsy, 22.2% of patients showed PI-RADS upgrading (PI-RADS > 3), and 29 patients (23%) exhibited a tumor upgrading. Patients with PI-RADS upgrading had a higher risk of csPCa compared to those without PI-RADS upgrading (42.9% vs. 9.18%, p < 0.05). PI-RADS upgrading was identified as an independent predictor for csPCa in follow-up biopsy (OR 16.20; 95% CI 1.17-224.60; p = 0.038). CONCLUSION: Patients with stable PI-RADS 3 findings may not require a follow-up biopsy. Instead, it is advisable to schedule an MRI, considering that PI-RADS upgrading serves as an independent predictor for csPCa.

Identification of genomic drivers for the therapeutic response of Cabozantinib in patients with metastatic renal cell carcinoma.

PURPOSE: Cabozantinib (CAB) as monotherapy or in combination with immune checkpoint inhibitors is used for systemic treatment of metastatic renal cell carcinoma (mRCC). However, little is known about predictors of treatment response to CAB. For this reason, known genomic drivers were examined to identify potential predictors of treatment response with CAB. METHODS: Twenty mRCC patients receiving monotherapy (≥ first-line) with CAB were prospectively included. DNA was extracted from archived primary tumors or metastatic tissue. Targeted DNA sequencing was performed using a gene panel including 328 genes (QIAseq Targeted DNA V3 Panel, Qiagen). The variant evaluation was performed using Varsome. The endpoints were treatment-failure-free-survival (TFFS) to CAB. RESULTS: 26% of patients received systemic RCC treatment as the primary option. Six patients were treated with CAB in first-line (1L) and 12 patients in ≥ 2L. The median follow-up after initiation of systemic treatment was 26.7 months (mo). The PBRM1 (7 alleles), SETD2 (7 alleles), VHL (11 alleles), and CHEK2 (14 alleles) genes were most frequently altered. The median time to TFFS was 10.5 mo (95% confidence interval (CI) 6.2-14.7 mo). There was a longer treatment response to CAB in patients with alterations of the SETD2 gene (SETD2 alteration median TFFS not reached vs. no SETD2 alterations 8.4 mo (95% CI 5.2-11.6 mo); p = 0.024). CONCLUSION: Pathogenic variant genes may indicate treatment response to systemic therapy in mRCC. Patients with alterations of the SETD2 gene show longer responses to CAB treatment.

A reliable transcriptomic risk-score applicable to formalin-fixed paraffin-embedded biopsies improves outcome prediction in localized prostate cancer.

BACKGROUND: Clinical manifestation of prostate cancer (PCa) is highly variable. Aggressive tumors require radical treatment while clinically non-significant ones may be suitable for active surveillance. We previously developed the prognostic ProstaTrend RNA signature based on transcriptome-wide microarray and RNA-sequencing (RNA-Seq) analyses, primarily of prostatectomy specimens. An RNA-Seq study of formalin-fixed paraffin-embedded (FFPE) tumor biopsies has now allowed us to use this test as a basis for the development of a novel test that is applicable to FFPE biopsies as a tool for early routine PCa diagnostics. METHODS: All patients of the FFPE biopsy cohort were treated by radical prostatectomy and median follow-up for biochemical recurrence (BCR) was 9 years. Based on the transcriptome data of 176 FFPE biopsies, we filtered ProstaTrend for genes susceptible to FFPE-associated degradation via regression analysis. ProstaTrend was additionally restricted to genes with concordant prognostic effects in the RNA-Seq TCGA prostate adenocarcinoma (PRAD) cohort to ensure robust and broad applicability. The prognostic relevance of the refined Transcriptomic Risk Score (TRS) was analyzed by Kaplan-Meier curves and Cox-regression models in our FFPE-biopsy cohort and 9 other public datasets from PCa patients with BCR as primary endpoint. In addition, we developed a prostate single-cell atlas of 41 PCa patients from 5 publicly available studies to analyze gene expression of ProstaTrend genes in different cell compartments. RESULTS: Validation of the TRS using the original ProstaTrend signature in the cohort of FFPE biopsies revealed a relevant impact of FFPE-associated degradation on gene expression and consequently no significant association with prognosis (Cox-regression, p-value > 0.05) in FFPE tissue. However, the TRS based on the new version of the ProstaTrend-ffpe signature, which included 204 genes (of originally 1396 genes), was significantly associated with BCR in the FFPE biopsy cohort (Cox-regression p-value < 0.001) and retained prognostic relevance when adjusted for Gleason Grade Groups. We confirmed a significant association with BCR in 9 independent cohorts including 1109 patients. Comparison of the prognostic performance of the TRS with 17 other prognostically relevant PCa panels revealed that ProstaTrend-ffpe was among the best-ranked panels. We generated a PCa cell atlas to associate ProstaTrend genes with cell lineages or cell types. Tumor-specific luminal cells have a significantly higher TRS than normal luminal cells in all analyzed datasets. In addition, TRS of epithelial and luminal cells was correlated with increased Gleason score in 3 studies. CONCLUSIONS: We developed a prognostic gene-expression signature for PCa that can be applied to FFPE biopsies and may be suitable to support clinical decision-making.

The Role of Multiparametric MRI (mpMRI) in the Prediction of Adverse Prostate Cancer Pathology in Radical Prostatectomy Specimen.

INTRODUCTION: Prostate cancer (PCa) risk stratification is essential in guiding therapeutic decision. Multiparametric magnetic resonance tomography (mpMRI) holds promise in the prediction of adverse pathologies (AP) after prostatectomy (RP). This study aims to identify clinical and imaging markers in the prediction of adverse pathology. METHODS: Patients with PCa, diagnosed by targeted biopsy after mpMRI and undergoing RP, were included. The predictive accuracy of mpMRI for extraprostatic extension (ECE), seminal vesicle infiltration (SVI), and lymph node positivity was calculated from the final histopathology. RESULTS: 846 patients were involved. Independent risk parameters include imaging findings such as ECE (OR 3.12), SVI (OR 2.55), and PI-RADS scoring (4: OR 2.01 and 5: OR 4.34). mpMRI parameters such as ECE, SVI, and lymph node metastases showed a high prognostic accuracy (73.28% vs. 95.35% vs. 93.38%) with moderate sensitivity compared to the final histopathology. The ROC analysis of our combined scoring system (D'Amico classification, PSA density, and MRI risk factors) improves the prediction of adverse pathology (AUC: 0.73 vs. 0.69). CONCLUSION: Our study supports the use of mpMRI for comprehensive pretreatment risk assessment in PCa. Due to the high accuracy of factors like ECE, SVI, and PI-RADS scoring, utilizing mpMRI data enabled accurate prediction of unfavorable pathology after RP.

Follow-up of vascular-targeted photodynamic therapy in a real-world setting.

PURPOSE: Vascular-targeted photodynamic therapy (VTP) is an approved treatment option for unilateral low-risk prostate cancer (PCa). METHODS: Patients with unilateral low- or intermediate-risk PCa undergoing hemiablation by VTP were evaluated in a real-world setting. Oncological outcome after VTP was measured by MRI-based re-biopsy at 12 and 24 months. Functional outcome after 1 year was investigated by IIEF-5 and IPSS questionnaires. Progression was defined as the evidence3 of ISUP ≥ 2 PCa. RESULTS: At any control biopsy (n = 46) after VTP, only 37% of patients showed no evidence of PCa. Recurrence-free survival was 20 months (95% CI 4.9-45.5) and progression-free survival was 38.5 months (95% CI 33.5-43.6 months). In-field and out-field recurrent PCa occurs in 37% (55% ISUP ≥ 2 PCa) and 35% (56% ISUP ≥ 2 PCa). Seventy-nine percent of patients preserved erectile function, respectively. Ten percent of patients presented long-term bladder outlet obstruction. None of the patients presented incontinence. CONCLUSION: Due to the high-recurrence in- and out-field recurrence rate in a mainly low-risk prostate cancer cohort, VTP has to be regarded critically as a therapy option in these patients. Pre-interventional diagnostic evaluation is the main issue before focal therapy to reduce the risk of tumor recurrence and progression.

The landscape of penile cancer research in Germany and Austria: a survey among professors in academic centers holding chair positions and results of a literature search.

BACKGROUND: Research on penile cancer (PeCa) is predominantly conducted in countries with centralized treatment of PeCa-patients. In Germany and Austria (G + A), no state-regulated centralization is established, and no information is available on how PeCa-research is organized. METHODS: Current research competence in PeCa was assessed by a 36-item questionnaire sent to all chairholders of urological academic centers in G + A. Based on PubMed records, all scientific PeCa-articles of 2012-2022 from G + A were identified. Current research trends were assessed by dividing the literature search into two periods (P1: 2012-2017, P2: 2018-2022). A bibliometric analysis was supplemented. RESULTS: Response rate of the questionnaire was 75%, a median of 13 (IQR: 9-26) PeCa-patients/center was observed in 2021. Retrospective case series were conducted by 38.9% of participating clinics, while involvement in randomized-controlled trials was stated in 8.3% and in basic/fundamental research in 19.4%. 77.8% declared an interest in future multicenter projects. 205 PeCa-articles were identified [median impact factor: 2.77 (IQR: 0.90-4.37)]. Compared to P1, P2 showed a significant increase in the median annual publication count (29 (IQR: 13-17) vs. 15 (IQR: 19-29), p < 0.001), in multicenter studies (79.1% vs. 63.6%, p = 0.018), and in multinational studies (53% vs. 28.9%, p < 0.001); the proportion of basic/fundamental research articles significantly declined (16.5% vs. 28.9%, p = 0.041). Four of the top-5 institutions publishing PeCa-articles are academic centers. Bibliometric analyses revealed author networks, primary research areas in PeCa, and dominant journals for publications. CONCLUSIONS: Given the lack of centralization in G + A, this analysis highlights the need for research coordination within multicenter PeCa-projects. The decline in basic/fundamental research should be effectively addressed by the allocation of funded research projects.