Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

[Urologic cancer care during the first wave of the COVID-19 pandemic : Role of federal cancer registration in Germany]. / Uroonkologische Therapie in der ersten Welle der COVID-19-Pandemie : Was sagen uns die Krebsregister der deutschen Bundesländer?

Urologic cancer care needs to be prioritized despite multiple health care restrictions during the coronavirus disease 2019 (COVID-19) pandemic. However, therapies and procedures may be delayed and complicated. In Germany, analysis of the multiple cancer registries provides insights into the actual numbers of treated patients. We provide a review on the registration of urologic cancer care during the first wave of the COVID-19 pandemic in Germany and on potential surgical complications of urologic interventions. We found that during the year 2020 there were generally fewer registrations of newly diagnosed patients with major urologic neoplasms in a representative federal database. The number of surgical interventions in patients with renal cell carcinoma and urothelial bladder cancer decreased, whereas equal numbers of radical prostatectomies were performed when compared to the year 2019. COVID-19 may increase non-urological postoperative complications following surgical treatment of urologic malignancies; however, available data are still very limited.

[Quality assessment of radical cystectomy-opportunities, risks, challenges]. / Qualitätsparameter bei der radikalen Zystektomie ­ Chancen, Risiken, Herausforderungen.

Radical cystectomy (RC) is the standard treatment for nonmetastatic muscle-invasive urothelial carcinoma of the urinary bladder. It is associated with relevant morbidity and mortality. After RC, the 5­year overall survival rate is approximately 60%. In the context of the present work, quality parameters of RC divided into oncological/functional criteria and freedom from complications are identified and summarized. A PubMed search was performed. In addition to early criteria such as negative surgical margins, performance of pelvic lymphadenectomy, creation of a continent urinary diversion or preservation of sexual function, long-term criteria were identified such as the absence of higher-grade postoperative complications, recurrence-free survival and the preservation of health-related quality of life. The early criteria are suitable for individualized therapy planning, whereas the long-term criteria can be used for quality monitoring.

[Enhanced imaging in urological endoscopy]. / Erweiterte Bildgebung in der urologischen Endoskopie.

White light cystoscopy and the concise documentation of pathological findings are standard diagnostic procedures in urology. Additional imaging modalities and technical innovations may support clinicians in the detection of bladder tumors. Modern endoscopy systems provide ultra-high-resolution imaging and the option of digital contrast enhancement. Photodynamic diagnostics and narrow band imaging are well-established in clinical routine and have shown significant benefits in the detection of bladder cancer. By means of multispectral imaging, different modalities can now be combined in real-time. Probe-based procedures such as optical coherence tomography (OCT) or Raman spectroscopy can further contribute to advanced imaging through an "optical biopsy" which may primarily improve diagnostics in the upper urinary tract. The aim of all techniques is to optimize the detection rate in order to achieve a more accurate diagnosis, resection and lower recurrence rates. Current research projects aim to digitalize the documentation of endoscopy and also make it more patient- and user-friendly. In the future, the use of image processing and artificial intelligence may automatically support the surgeon during endoscopy.

Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surface.

BACKGROUND: Bladder cancer cells orchestrate tumour progression by pro-inflammatory cytokines. Cytokines modulate the local tumour microenvironment and increase the susceptibility of tumour distant tissues for metastasis. Here, we investigated the impact of human bladder cancer cell derived factors on the ability to modulate and activate human vascular endothelial cells. METHODS: The pro-inflammatory and pro-coagulatory potential of four different bladder cancer cell lines was accessed by qRT-PCR arrays and ELISA. Modulation and activation of endothelial cells was studied in microfluidic devices. Clinical relevance of our findings was confirmed by immune histology in tissue samples of bladder cancer patients and public transcriptome data. RESULTS: The unbalanced ratio between interleukin (IL)-1 and IL-1 receptor antagonist (IL-1ra) in the secretome of bladder cancer cells converted the quiescent vascular endothelium into a pro-adhesive, pro-inflammatory, and pro-coagulatory surface. Microfluidic experiments showed that tumour cell induced endothelial cell activation promoted leukocyte recruitment and platelet adhesion. Human bladder cancer tissue analysis confirmed that loss of IL-1ra and elevated IL-1 expression was associated with enhanced cancer progression. CONCLUSIONS: Our data indicate that IL-1 and IL-1ra were dysregulated in bladder cancer and could facilitate tumour dissemination through endothelial cell activation. Targeting the IL-1/IL-1ra axis might attenuate tumour-mediated inflammation and metastasis formation.

[The role of the vesical imaging-reporting and data system (VI-RADS) for bladder cancer diagnostics-status quo]. / Bedeutung der VI-RADS-Klassifikation für die Bildgebung beim Harnblasenkarzinom ­ Stand der Dinge.

Initial clinical and pathological diagnostic workup of urinary bladder cancer is based on cystoscopy, transurethral resection of suspicious lesions, and computed tomography when indicated. Accurate staging is necessary for further therapeutic decision-making. This review summarizes the current status of multiparametric magnetic resonance imaging (mpMRI) and the vesical imaging-reporting and data system (VI-RADS) classification. MpMRI may improve the accuracy of assessment of local tumor invasion compared to conventional imaging alone. VI-RADS standardizes reporting of MRI staging and classifies the likelihood of muscle-invasive bladder cancer into five categories. Preliminary data suggest low interobserver variability. However, prospective multicenter studies are necessary to validate the VI-RADS classification. Progress in functional, molecular, and hybrid imaging may further improve the accuracy of clinical tumor and nodal staging for bladder cancer.

[The development of real-time multispectral imaging for the diagnostics of bladder cancer]. / Entwicklung der Echtzeitmultispektralbildgebung für die Diagnostik des Harnblasenkarzinoms.

The performance of white light (WL) cystoscopy in the diagnostics of bladder cancer can be optimized by the use of modern imaging modalities, such as photodynamic diagnostics (PDD) and narrow band imaging (NBI). Real-time multispectral imaging (rMSI) enables simultaneous imaging of reflectance and fluorescence modalities in multiple spectral bands. We created a multiparametric cystoscopy image by digital overlapping of several modalities, e.g. WL, enhanced vascular contrast (EVC), raw fluorescence mode, protoporphyrin IX and autofluorescence (AF). The technical development and the subsequent clinical implementation of rMSI required a structured preclinical evaluation process, including both ex vivo and in vivo trials before the technology can be applied in patients. This review article presents the phases of testing, validation and the first clinical application of rMSI in urological endoscopy.

[Urology training in Germany: international comparison of educational concepts and satisfaction]. / Urologische Facharztausbildung im internationalen Vergleich: Wo stehen wir in Deutschland?

BACKGROUND: The training of residents in urology is challenged by global trends in surgical education, increasing technological developments, subspecialization of the field and working hour regulations for physicians. Currently, there is no standardized curriculum in Europe and significant international differences exist in the education of residents. OBJECTIVES: We aimed to comprehensively map the state of urological training in an international comparison. MATERIALS AND METHODS: A selective literature review was conducted using the following keywords: "urology, training, residents". RESULTS: Recent surveys have shown that urology training in Germany is subject to relatively few regulations on content, time and space when compared to other countries. A lack of a structured curriculum is considered as the main factor leading to dissatisfaction of the residents. Increasing work load, lack of surgical training and limited flexibility in family or research planning have been mentioned as barriers for successful training. CONCLUSION: Structured and validated competence assessments and not "minimum numbers of operations" may help improve surgical training. An objective nationwide examination at the end of residency may be useful for international benchmarking.

[Biopsy techniques in the upper urinary tract for the diagnosis of urothelial carcinoma: systematic review]. / Biopsietechniken im oberen Harntrakt zur Diagnostik des Urothelkarzinoms: systematische Übersicht.

BACKGROUND: The diagnostic accuracy of ureteroscopic biopsies in the upper urinary tract is limited by technical difficulties during extraction and small sample size. OBJECTIVES: To evaluate the impact of different techniques and instruments on the histopathologic quality and diagnostic yield of extracted samples as well as the predictive value of clinical grading and staging on final pathologic stage at radical nephroureterectomy. MATERIALS AND METHODS: For this systematic review, we searched PubMed and Embase databases for original publications and meeting abstracts according to the PRISMA guidelines. RESULTS: Overall, we included 23 studies which comprised a total of 1547 biopsies for the investigation of diagnostic yield and 778 patients for the assessment of grade and stage concordance. We found that the median diagnostic yields of big retrograde 2F [french] forceps, antegrade 3F forceps and baskets in combination with forceps were 92% (range 83-100), 72% (50-90) and 91% (78-94), respectively. Median rates of grade concordance and upgrading across all techniques ranged between 78-89% and 5-16%, respectively, without relevant differences. CONCLUSIONS: The choice of biopsy technique affects the ability to diagnose upper tract urothelial carcinoma. The correct determination of pathologic grading is comparable between different techniques. The combination of biopsy forceps and baskets during ureterorenoscopy seems to achieve optimal diagnostic accuracy.

The concentration of console surgeons: prospective evaluation of the loss of attention in robotic-assisted procedures.

To prospectively evaluate the possible loss of attention among console surgeons performing robotic-assisted procedures using a validated psychological test. The concentration of one console surgeon was assessed before and after 25 robotic-assisted procedures (radical prostatectomies) using the validated d2 attention test (computer-assisted, Hogrefe test systems, Germany). Error frequency, work rate, and accuracy of task performance were evaluated as parameters of the fluctuation in concentration. Data were correlated with clinical parameters, including console times, positive surgical margin rates and the use of a nerve-sparing procedure. Pre- and post-operative test results revealed no differences in the number of items performed, but a significant decline in the error-corrected performance between the pre- and post-operative tests was observed with increasing console time (p = 0.046; median console time 123 min.). No differences in the pre-operative tests for consecutive procedures (mean time between procedures 93 min.) were found, whereas the number of errors (missed items) increased in the post-operative tests (p = 0.0025). The measured differences in test results showed no association with the positive surgical margin rate. A planned nerve-sparing procedure tended to result in a lower level of concentration found in pre-operative testing (p = 0.07). Concentration decrease and loss of attention during robotic-assisted procedures can be measured validly using the d2 attention test. Longer console times lead to loss of attention but consecutive procedures do not decrease the test or surgical performance. Further studies need to address whether similar effects apply to the comparable open or other robotic procedures or to different levels of surgeons experience.

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer.

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n=57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P=0.0009) and ESR1 (P=0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR=2.11, CI 1.11-4.21, P=0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P=0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR=4.41, CI 1.53-18.71, P=0.004) and Luminal B (HR=1.96, CI 0.99-4.08, P=0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.

Wide-field autofluorescence-guided TUR-B for the detection of bladder cancer: a pilot study.

PURPOSE: The aim of this pilot study was to assess the feasibility and value of wide-field autofluorescence imaging (AFI) for the detection of bladder cancer during transurethral resection of the bladder (TUR-B). METHODS: For imaging, the D-Light/AF System (Karl Storz GmbH, Tuttlingen, Germany) and a customized band pass filter (≈ 480-780 nm) at the eyepiece of the endoscope were used. The excitation light wavelength was 440 nm. Representative spectral measurements of tissue autofluorescence (AF) were performed using a spectrometer attached behind the AF band pass filter in selected patients. During TUR-B, cystoscopy was performed in white light (WL) followed by wide-field AFI. Lesions were classified as suspicious or normal using either modality. RESULTS: Representative spectral measurements using excitation at a wavelength of 440 nm resulted in significantly lower fluorescence intensity of malignant versus non-malignant tissue. Overall, 56 lesions (30 cancerous and 26 non-malignant) in 25 patients were assessed and classified by wide-field AFI. Papillary tumors as well as flat lesions lacked the green fluorescence seen in normal urothelium, thus emerging as "brown-reddish" areas. When compared with histopathological findings, the pooled per-lesion sensitivity and specificity for AF were 96.7 and 53.8%, respectively. For WL these values were 86.7 and 69.2%, respectively. CONCLUSION: Wide-field AFI imaging during TUR-B is simple and easy to use. Our preliminary data suggest that AFI has the potential to increase the detection rates of bladder tumors compared with WL without the need of intravesical instillation prior to the procedure.

[Modern endoscopic imaging tools for urothelial carcinoma of the urinary bladder]. / Moderne endoskopische Bildgebungsverfahren für das Urothelkarzinom der Harnblase.

Cystoscopy is the gold standard for the initial diagnosis of urothelial carcinoma in the urinary bladder (UCB). White light exhibits significant limitations in its ability to detect flat lesions or carcinoma in situ. Photodynamic Diagnosis (PDD) and Narrow Band Imaging (NBI) are established techniques which may improve the detection rates of UCB and reduce the risk of recurrence. Multiple novel tools have been developed in order to improve the diagnostic accuracy of endoscopic procedures, including Digital Contrast Enhancement Technology, Confocal Laser Endomicroscopy (CLE) and Optical Coherence Tomography (OCT). In future, spectral analysis of urothelial lesions may be achieved by Raman spectroscopy, thus providing information about biological alterations in the tissue. Furthermore, molecular imaging may allow specific targeting by fluorescent antibodies or small molecule agents, thus enabling differential diagnosis of suspicious lesions. Software-based approaches have been developed to incorporate computer-aided diagnosis and improve digital documentation of endoscopic findings. This study reviews current and future developments in the field of modern endoscopy of the urinary bladder and discusses the different approaches.

[Microscopic hematuria : Reasonable and risk-adapted diagnostic evaluation]. / Mikrohämaturie : Sinnvolle und risikoadaptierte Abklärung.

BACKGROUND: Microscopic hematuria that is not explained by an obvious underlying condition is a frequent and often an incidental finding that commonly triggers urological or nephrological evaluation. Potential underlying conditions range from benign to severe malignant diseases of the kidneys and urinary tract. MATERIALS AND METHODS: A nonsystematic literature search was performed, focusing on potential urological and nephrological causes of hematuria. National and international guidelines were considered and diagnostic as well as follow-up strategies are discussed. We provide a recommendation for practices in the clinical evaluation of hematuria. RESULTS: The overall prevalence for microscopic hematuria is estimated at approximately 2%, whereas risk populations show an increase to around 30%. In 13-35% of patients presenting with microscopic hematuria, a medical or surgical intervention is required. Malignant tumors of the kidneys or urinary tract can be diagnosed in 2.6-4% of all patients and in up to 25.8% of at-risk populations. "Idiopathic microscopic hematuria" without an obvious underlying medical condition accounts for approximately 80% of patients with asymptomatic hematuria. After exclusion of nephrological diseases, standard diagnostic procedures by means of medical history, physical and laboratory examination as well as ultrasound of the kidneys and the urinary tract should be performed. In the presence of risk factors, an extended diagnostic work-up using cystoscopy, urinary cytology, and cross-sectional imaging of the upper urinary tract is indicated. CONCLUSION: Evidence-based strategies of a risk-adapted diagnostic evaluation for microscopic hematuria are not available. The development of reliable clinical and molecular markers offers great potential for the identification of patients at higher risk for harboring severe diseases.

[When should the primary tumor of metastatic bladder or prostate cancer be treated using a nonsurgical regimen?] / Wann ist der Primärtumor eines Harnblasen- bzw. Prostatakarzinoms in der metastasierten Situation durch eine nicht-operative Maßnahme zu therapieren?

BACKGROUND: Patients with metastatic and locally advanced bladder or prostate cancer may suffer from pelvic symptoms such as pain, obstruction, and hemorrhage. Local tumor growth is associated with significant morbidity and systemic therapy is often ineffective. Local therapies such as bladder irrigation, transurethral resection of the prostate, and fulguration of bleeding vessels provide relief but often require repeated treatments. OBJECTIVES: The aim of this work was to review the current status of palliative pelvic radiotherapy for metastatic bladder and prostate cancer. MATERIALS AND METHODS: The available literature was evaluated and treatment recommendations are proposed depending on different clinical scenarios. RESULTS: To date, no standard regimen exists for the delivery of palliative pelvic radiotherapy. Various radiotherapy schedules manage successful and long-term palliation of pelvic symptoms in most patients and result in acceptable toxicity. For bladder cancer, the most common dose and fractionation regimens range from 20 Gy in 5 fractions to 40 Gy in 20 fractions. Some retrospective studies evaluated 6 weekly fractions of 6 Gy to a total dose of 36 Gy. For prostate cancer, the most common dose and fractionation regimes range from 30 Gy in 10 fractions to 50 Gy in 25 fractions. The symptomatic response rate is between 70 and 95%. CONCLUSIONS: Pelvic radiotherapy for patients with metastatic and locally advanced bladder or prostate cancer provides effective and long-term palliation of a variety of symptoms such as pain, obstruction, and hemorrhage, with acceptable toxicity. Future studies should investigate the optimal target dose and fractionation schedule.