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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.

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 5‑year 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.

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.

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.

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.

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.

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.

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.

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.

Background: There are numerous randomized trials to guide the management of patients with localized (and metastatic) prostate cancer, but only a few (mostly retrospective) studies have specifically addressed node-positive patients. Therefore, there is uncertainty regarding optimal treatment in this situation. Current guidelines recommend long-term androgen deprivation therapy (ADT) alone or radiotherapy plus long-term ADT as treatment options., Objectives: This overview summarizes the existing literature on the use of radiotherapy for node-positive prostate cancer as definitive treatment and as adjuvant or salvage therapy after radical prostatectomy. In this context, we also discuss several PET tracers in the imaging evaluation of patients with biochemical recurrence of prostate cancer after radical prostatectomy. As for definitive treatment, retrospective studies suggest that ADT plus radiotherapy improves overall survival compared with ADT alone. These studies also consistently demonstrated that many patients with node-positive prostate cancer can achieve long-term survival - and are likely curable - with aggressive therapy., Results: The beneficial impact of adjuvant radiotherapy on survival in patients with pN1 prostate cancer seems to be highly influenced by tumor characteristics. Men with ≤ 2 positive lymph nodes in the presence of intermediate- to high-grade disease, or positive margins, and those with 3 or 4 positive lymph nodes are the ideal candidates for adjuvant radiotherapy (plus long-term ADT) after surgery., Conclusion: There is a need for randomized trials to further examine the potential role of radiotherapy as either definitive or adjuvant treatment, for patients with node-positive prostate cancer.

Background: Lymphovascular invasion (LVI) represents a surrogate marker for micrometastatic urothelial carcinoma of the bladder (UCB)., Objectives: We evaluated whether D2-40 immunhistochemistry (IHC) alters detection of LVI when compared to conventional HE (hematoxylin-eosin) staining of UCB specimens in a blinded fashion., Material and Methods: HE- and D2-40-IHC-stained representative sections of 80 patients after radical cystectomy (RC) were re-reviewed. LVI detection rates were recorded and compared after blinded evaluation., Results: LVI was present in 53 patients (66.3%) in HE-stained sections and in 44 patients (55%) in D2-40 stainings. In 13 patients, LVI (16.3%) was found in HE stained sections but not confirmed when IHC was applied (false positive when using IHC as a reference standard). D2-40 IHC identified LVI in 4 additional patients (5%) who were classified as LVI negative in conventional HE staining (false negative). 52 patients (65%) were lymph node negative (pN0), 21 of whom (40.4%) were LVI positive in conventional HE sections and 16 of whom (30.8%) were LVI positive in IHC. In 9 pN0 patients (17.3%), LVI was diagnosed in HE sections but not confirmed by IHC (false positive). D2-40 IHC identified LVI in 4 additional patients (7.7%) who were node negative and classified as LVI negative in conventional HE staining (false negative). In patients who experienced recurrence (n=35) and who were classified as pN0 at the time of RC, HE staining resulted both in false-positive (n=2; 5.7%) and false-negative (n=3; 8.6%) findings., Conclusion: Different detection rates of LVI were observed when using IHC with D2-40 in UCB patients compared to conventional HE staining. The routine use of D2-40 IHC should be considered in clinical trial design to improve risk stratification of pN0 patients after RC.

Local invasion of cancer cells occurs early during the progression of urothelial carcinoma. Micrometastatic disease and the presence of nodal metastases are major causes of cancer-specific mortality following radical surgery. Only surrogate markers for aggressive and micrometastatic disease have been identified. The metastatic cascade is complex, including multiple steps from initial invasion to colonization and proliferation at distant sites. The initial mechanisms of cancer cell dissemination in urothelial carcinoma are poorly understood. Various proteases, chemokines and growth factors are involved in this process and alterations of the lymphatic system may promote systemic spread. There is a high demand for therapeutic targeting of the metastatic process. Functional preclinical studies in representative models are therefore required to better elucidate the multiple steps of progression. We review the current knowledge on factors associated with metastasis in urothelial carcinoma. Preclinical approaches to identify key player molecules for invasion and to develop new therapeutic strategies are discussed.

Background: The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients <75 and >75 years of age (median follow-up was 42 months)., Patients and Methods: Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed., Results: The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p<0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p<0.001) and CSS (HR=1.27; p=0.018)., Conclusions: An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.

Objective: Pre-cystectomy nomograms with a high predictive ability for locally advanced urothelial carcinomas of the bladder would enhance individual treatment tailoring and patient counselling. To date, there are two currently not externally validated nomograms for prediction of the tumour stages pT3-4 or lymph node involvement., Materials and Methods: Data from a German multicentre cystectomy series comprising 2,477 patients with urothelial carcinoma of the bladder were applied for the validation of two US nomograms, which were originally based on the data of 726 patients (nomogram 1: prediction of pT3-4 tumours, nomogram 2: prediction of lymph node involvement). Multivariate regression models assessed the value of clinical parameters integrated in both nomograms, i.e. age, gender, cT stage, TURB grade and associated Tis. Discriminative abilities of both nomograms were assessed by ROC analyses; calibration facilitated a comparison of the predicted probability and the actual incidence of locally advanced tumour stages., Results: Of the patients, 44.5 and 25.8% demonstrated tumour stages pT3-4 and pN+, respectively. If only one case of a previously not known locally advanced carcinoma (pT3-4 and/or pN+) is considered as a staging error, the rate of understaging was 48.9% (n=1211). The predictive accuracies of the validated nomograms were 67.5 and 54.5%, respectively. The mean probabilities of pT3-4 tumours and lymph node involvement predicted by application of these nomograms were 36.7% (actual frequency 44.5%) and 20.2% (actual frequency 25.8%), respectively. Both nomograms underestimated the real incidence of locally advanced tumours., Conclusions: The present study demonstrates that prediction of locally advanced urothelial carcinomas of the bladder by both validated nomograms is not conferrable to patients of the present German cystectomy series. Hence, there is still a need for statistical models with enhanced predictive accuracy.

Background: Few and partially contradictory data are available regarding the prognostic signature of downstaging of muscle-invasive clinical tumour stages in patients treated with radical cystectomy., Materials and Methods: Clinicopathological parameters of 1,643 patients (study group, SG) treated with radical cystectomy due to muscle-invasive urothelial bladder cancer were summarized in a multi-institutional database. Patients of the SG fulfilled the following conditions: clinical tumour stage T2 N0 M0 and no administration of neoadjuvant radiation or chemotherapy. Cancer-specific survival (CSS) rates were calculated referring to pathological tumour stages in cystectomy specimens (pT2) (mean follow-up: 51 months). Furthermore, a multivariable model integrating clinical information was developed in order to predict the probability of downstaging., Results: A total of 173 patients (10.5%) of the SG presented with downstaging in pathological tumour stages (pT0: 4.8%, pTa: 0.4%, pTis: 1.3%, pT1: 4.1%); 12 of these patients had positive lymph nodes (7%, in comparison with 21% pN+ of pT2 tumours and 43% of >pT2 tumours). Patients with tumour stages pT2 had CSS rates after 5 years of 89, 69 and 46%, respectively (p<0.001). In a multivariable Cox model the presence of pathological downstaging resulted in a significant reduction of cancer-specific mortality (HR 0.30; 95% CI 0.18-0.50). By logistic regression analysis the date of TURB (benefit for more recent operations) was identified as the only independent predictor for downstaging of muscle-invasive clinical tumour stages. Age, gender, grading and associated Tis in the TURB did not reveal any significant influence., Conclusion: Patients with muscle-invasive clinical tumour stages and downstaging in cystectomy specimens represent a subgroup with significantly enhanced CSS rates. Further trials that integrate the parameters tumour size, stages cT2a vs cT2b and focality are required in order to define the independent prognostic signature of downstaging of tumour stages more precisely.

Background: Brachytherapy (BT) is an established treatment option for low risk prostate cancer. The aim of this study was to determine the long-term complications and side effects of the procedure in an up to 13 year long single center follow-up analysis., Material: A total of 505 patients were treated by BT for prostate cancer between May 1991 and August 2005. Cohort I (n=412; May 1991 to November 2003) was evaluated by written questionnaire (modified ICS male) and patient chart evaluation in terms of side effects and secondary interventions. In cohort II (n=148; January 2002 to August 2005) perioperative complications were investigated., Results: The mean follow-up was 5.5 years. Perioperative complications were present in 5.4% of patients. Transurethral resection of the prostate was a common secondary intervention, performed in 7% of cases. The rate of incontinence was 6.3% in the long-term follow-up, the rate of potency was 43.5% in those patients who were potent before BT and no hormonal manipulation was performed at any time., Conclusion: BT is a minimally invasive procedure for the treatment of localised "low risk" prostate cancer. Perioperative complications are rare, secondary intervention may be necessary and the patient has to be informed of possible impotence, incontinence and lack of ejaculation.