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In the case presented, we suspect the toothpick to have perforated the duodenal wall and completely migrated into the renal pelvis of the right kidney due to the location of the toothpick high up in the renal pelvis as has been described before [[4]]. Abdominal CT showed hypoperfusion of the right kidney and hydronephrosis II° with enhancement of the wall of the renal pelvis, as well as the upper third of the right ureter. Abbreviations URS ureterorenoscopy UUT upper urinary tract Introduction Foreign bodies in the upper urinary tract (UUT) represent a rare, but well-documented phenomenon. An abdominal CT scan showed a contrast enhanced renal pelvis and ureter, as well as an intraluminal, linear contrast media defect, adjacent to the wall of the ureter. [Extracted from the article]

Artificial intelligence (AI) aims at simulating, or approximating, human intelligence in machines with the goal of reproducing, replacing or even improving brain tasks of perception, reasoning, and learning. For example, we have seen AI/ML models treating the ordinal variable Gleason Score as a continuous variable or age as any number between zero and infinity. And do the AI/ML models improve predictions above and beyond current standard of care and models based on already known predictors of the outcome?. [Extracted from the article]

The article discusses the use of artificial intelligence (AI) and machine learning (ML) in modern medicine. It highlights the potential applications of AI and ML in areas such as pathology, imaging interpretation, and data analysis. The article also raises concerns about the validation and clinical relevance of AI prediction models, citing examples of flawed models in sepsis prediction and COVID-19 diagnosis. The authors emphasize the need for standardized reporting and transparency in AI research, as well as the importance of considering biases and limitations in biomedical datasets. They conclude that the successful implementation of AI in clinical practice depends on rigorous methodology and replication of results. [Extracted from the article]

Objective: To provide a chronological overview of the evolution of continent urinary diversion (CUD) over the last 50 years and to highlight important milestones. Methods: We performed an extensive literature review and analysed different forms of urinary diversion worldwide. After the evaluation of surgical techniques, we assessed the advantages and disadvantages of assorted CUD approaches based on published long‐term follow‐up data. Results: A wide variety of surgical options for CUD is available and feasible to date, although consensus among urologists regarding the 'gold standard' is still lacking. Several forms of orthotopic bladder substitutes and continent cutaneous urinary reservoirs have been shown to provide excellent long‐term results. Conclusion: The last 50 years of CUD have seen constant evolution and refinement of techniques, but the best surgical approach remains unclear and there is no 'one‐size‐fits‐all' option, but rather tailor‐made approaches are necessary to ensure patient satisfaction. [ABSTRACT FROM AUTHOR]

Advanced-stage prostate cancer (PCa) patients are often diagnosed with bone metastases. Bone metastases remain incurable and therapies are palliative. PCa cells prevalently cause osteoblastic lesions, characterized by an excess of bone formation. The prevailing concept indicates that PCa cancer cell secrete an excess of paracrine factors stimulating osteoblasts directly or indirectly, thereby leading to an excess of bone formation. The exact mechanisms by which bone formation stimulates PCa cell growth are mostly elusive. In this review, the mechanisms of PCa cancer cell osteotropism, the cancer cell-induced response within the bone marrow/bone stroma, and therapeutic stromal targets will be summarized. [ABSTRACT FROM AUTHOR]

Background Matrix metalloproteinases (MMP), particularly MMP-2 and MMP-9, participate in tumour progression and metastasis in various cancers. Their significance in urothelial cancer of the bladder (UCB) is unclear. Expression analysis of MMP-2 and MMP-9 in tissue microarrays (TMA) constructed of corresponding samples from histopathological normal urothelium, tumour centre and invasion front of primary tumours and lymph-node (LN) metastases might help to elucidate their relevance in UCB. Method MMP-2 and MMP-9 expression was evaluated in TMA of 150 surgically treated LN-positive UCB patients. Biomarker expression was correlated with tumour characteristics (primary tumour and LN stage, number, total diameter and extracapsular extension of LN metastases) and overall survival. Results While there was a significant increase in MMP-9 expression from normal urothelium over primary tumours to metastases (median scores: 20, 50, 65; p<0.005), no such trend was observed in MMP-2 (median scores: 5, 22, 10; p<0.005). A comparison of expression in the tumour centre and the invasion front showed no difference in both MMP. No association between expression and histopathological tumour characteristics was identified. There was a non-significant trend for a more favourable outcome for patients with high MMP-2 expression in primary tumours. Conclusion In LN-positive UCB, MMP-2 and MMP-9 expression was not increased at the invasion front, suggesting an infiltration strategy independent of MMP-2 and MMP-9 activity. Larger series are needed to detect a potential significant trend for favourable outcome in cancers with high MMP-2 expression. INSET: Take-home messages. [ABSTRACT FROM AUTHOR]

Abstract: Background: The tumor microenvironment is important for progressive and metastatic disease. Objective: To study the hypothesis that prostate fibroblasts have differential ability to induce castration-resistant prostate cancer (PCa) and metastatic progression and whether this effect might vary depending on the zonal origin of the fibroblast. Design, setting, and participants: Human prostate fibroblasts from the peripheral (PZ), transition (TZ) and central (CZ) zones of radical prostatectomy specimens (n =13) were isolated and compared for their ability to promote androgen independence and metastatic progression in androgen-responsive PCa lymph node carcinoma of the prostate (LNCaP) cells in vivo. Interventions: By coinoculating marginally tumorigenic LNCaP cells with PZ or TZ and by altering host hormonal milieu, a series of tumorigenic and metastatic LNCaP epithelial sublines–P4, P4-2 (derivatives from interaction with PZ), T4, and T4-2 (derivatives from interaction with TZ)–were established and characterized. Measurements: In vivo and in vitro evaluation of induction of tumor growth and metastatic potential. Results and limitations: 1) LNCaP sublines were permanently altered in their cytogenetic and biologic profiles after cellular interaction with prostate stromal fibroblasts. LNCaP sublines grew faster under anchorage-dependent and -independent conditions, expressed 1–12-fold more prostate-specific antigen in vitro than LNCaP cells, and gained metastatic potential; 2) zonal differences of stromal fibroblasts in their ability to induce the growth and progression of LNCaP tumors as xenografts in mice may exist but need further analysis; 3) PZ-conditioned medium induced more anchorage-independent growth of LNCaP cells in vitro. TZ had a higher growth rate and were more sensitive to dihydrotestosterone. Conclusions: We demonstrate that prostate fibroblasts have growth inductive potential on PCa cells and affect their subsequent progression to castration resistance and development of a metastatic phenotype. [Copyright &y& Elsevier]

Pelvic lymphadenectomy is widely accepted as an essential part of radical cystectomy. It provides important information (number of lymph nodes involved, tumor volume, capsular perforation) for prognosis, which may help identify patients at increased risk for progression. More important, there is a growing body of evidence indicating that meticulous, extended pelvic lymphadenectomy may cure a substantial number of patients who would otherwise develop local recurrences or distant metastases. Furthermore, extended bilateral lymph node dissection facilitates cystectomy, makes it safer to perform and does not substantially alter morbidity of the operation. [Copyright &y& Elsevier]

Assesses the effect of suramin on the growth of the androgen-dependent human prostate cancer cell line LNCaP and its androgen-independent subline C4-2 both in vivo and in vitro. Materials and method of study; Statistical analysis; In vivo and in vitro assessment of suramin activity.

Background. Several factors are implicated in renal stone formation and peak incidence of renal colic admissions to emergency departments (ED). Little is known about the influence of potential environmental triggers such as lunar gravitational forces. We conducted a retrospective study to test the hypothesis that the incidence of symptomatic renal colics increases at the time of the full and new moon because of increased lunar gravitational forces. Methods. We analysed 1500 patients who attended our ED between 2000 and 2010 because of nephrolithiasis-induced renal colic. The lunar phases were defined as full moon ± 1 day, new moon ± 1 day, and the days in-between as "normal" days. Results. During this 11-year period, 156 cases of acute nephrolithiasis were diagnosed at the time of a full moon and 146 at the time of a new moon (mean of 0.4 per day for both). 1198 cases were diagnosed on "normal" days (mean 0.4 per day). The incidence of nephrolithiasis in peak and other lunar gravitational phases, the circannual variation and the gender-specific analysis showed no statistically significant differences. Conclusion. In this adequate powered longitudinal study, changes in tractive force during the different lunar phases did not influence the incidence of renal colic admissions in emergency department. [ABSTRACT FROM AUTHOR]

Tumors strongly depend on their surrounding tumor microenvironment (TME) for growth and progression, since stromal elements are required to generate the optimal conditions for cancer cell proliferation, invasion, and possibly metastasis. Prostate cancer (PCa), though easily curable during primary stages, represents a clinical challenge in advanced stages because of the acquisition of resistance to anti-cancer treatments, especially androgen-deprivation therapies (ADT), which possibly lead to uncurable metastases such as those affecting the bone. An increasing number of studies is giving evidence that prostate TME components, especially cancer-associated fibroblasts (CAFs), which are the most abundant cell type, play a causal role in PCa since the very early disease stages, influencing therapy resistance and metastatic progression. This is highlighted by the prognostic value of the analysis of stromal markers, which may predict disease recurrence and metastasis. However, further investigations on the molecular mechanisms of tumor–stroma interactions are still needed to develop novel therapeutic approaches targeting stromal components. In this review, we report the current knowledge of the characteristics and functions of the stroma in prostate tumorigenesis, including relevant discussion of normal prostate homeostasis, chronic inflammatory conditions, pre-neoplastic lesions, and primary and metastatic tumors. Specifically, we focus on the role of CAFs, to point out their prognostic and therapeutic potential in PCa. [ABSTRACT FROM AUTHOR]

The article offers insight on the comparison between open and robot-assisted cystectomy as treatment options for invasive bladder cancer. Topics discussed include an overview of each of these cystectomy procedures, the medical records of the patients, the revolution of invasive surgery, the quality of life, and the measurement of radical cystectomy.

The article informs that the study "Sentinel Node Biopsy for Prostate Cancer: Report From a Consensus Panel Meeting," by researcher H. G. van der Poel and colleagues. It is noted that the study report the findings of a consensus panel meeting on sentinel node (SN) biopsy at the time of radical prostatectomy. It is noted that authors are to be complimented on their effort to establish standard definitions, techniques, and reporting of outcomes of SN detection.

Simple Summary: The diagnosis of primary upper urinary tract urothelial carcinoma is challenging and may necessitate invasive procedures. In this study, through analysing two cohorts, we evaluated the diagnostic accuracy of drug-induced turbulence in the upper urinary tract and non-invasive urine sampling in the diagnosis of primary upper tract urothelial carcinoma and upper tract urothelial carcinoma recurrence during follow-up after radical cystectomy for primary bladder cancer. As a diagnostic tool, cytology of pharmacologically forced diuresis performs better in patients with invasive upper tract urothelial carcinoma and concomitant carcinoma in situ. As a method of surveillance, positive cytology of pharmacologically forced diuresis was related to cancer recurrence and could even detect recurrence in the urethra in cases involving an orthotopic bladder substitute. In conclusion, urine cytology in pharmacologically forced diuresis may be useful in patients with suspected upper tract urothelial carcinoma, especially in cases with contraindications for imaging or when achieving endoscopic access to the upper urinary tract is difficult. We performed a urine cytology analysis of a pharmacologically induced diuresis for the diagnosis of upper tract urothelial carcinoma. To evaluate the diagnostic value of cytology of pharmacologically forced diuresis, an initial cohort of 77 consecutive patients with primary upper tract urothelial carcinoma treated via radical surgery was enrolled. To evaluate pharmacologically forced diuresis cytology as a follow-up procedure, a second cohort of 1250 patients who underwent a radical cystectomy for bladder cancer was selected. In the first cohort, the sensitivity of cytology of pharmacologically forced diuresis in patients with invasive, high-grade, low-grade, and concomitant carcinoma in situ was 8%, 9%, 0%, and 14%, respectively. In the second cohort, cytology of pharmacologically forced diuresis was positive in 30/689 (4.3%) patients, in whom upper urinary tract recurrence was present in 21/30 (70%) of cases, and urethral recurrence was present in 8/30 (26%) of cases. As a follow-up tool, cytology of pharmacologically forced diuresis showed a sensitivity, specificity, and positive and negative predictive values of 60%, 99%, 70%, and 98%, respectively. Overall, as a diagnostic tool, the sensitivity of cytology of pharmacologically forced diuresis is slightly better in patients with invasive upper tract urothelial carcinoma and concomitant carcinoma in situ. As a follow-up method, positive cytology of pharmacologically forced diuresis is strongly related to cancer recurrence and can reveal urethral recurrence. Cytology of pharmacologically forced diuresis might be useful in cases with contraindications for imaging or when achieving endoscopic access to the upper urinary tract is difficult. [ABSTRACT FROM AUTHOR]

The article offers information on enhanced recovery after surgery (ERAS) which is a multidisciplinary, multielement care pathway approach focused on standardizing and improving perioperative management. It mentions that ERAS is for radical cystectomy with the important factor in postoperative management of patients undergoing surgery in the field of urology.

Objective: To assess the long‐term safety of nerve‐sparing radical prostatectomy (NSRP) in men with high‐risk prostate cancer (PCa) by comparing survival outcomes, disease recurrence, the need for additional therapy, and perioperative outcomes of patients undergoing NSRP to those having non‐NSRP. Patients and methods: We included consecutive patients at a single, academic centre who underwent open RP for high‐risk PCa, defined as preoperative prostate‐specific antigen level of > 20 ng/mL and/or postoperative International Society of Urological Pathology Grade Group 4 or 5 (i.e., Gleason score ≥ 8) and/or ≥pT3 and/or pN1 assessing the RP and lymph node specimen. We calculated a propensity score and used inverse probability of treatment weighting to match baseline characteristics of patients with high‐risk PCa who underwent NSRP vs non‐NSRP. We analysed oncological outcome as time‐to‐event and calculated hazard ratios (HRs). Results: A total of 726 patients were included in this analysis of which 84% (n = 609) underwent NSRP. There was no evidence for the positive surgical margin rate being different between the NSRP and non‐NSRP groups (47% vs 49%, P = 0.64). Likewise, there was no evidence for the need for postoperative radiotherapy being different in men who underwent NSRP from those who underwent non‐NSRP (HR 0.78, 95% confidence interval [CI] 0.53–1.15). NSRP did not impact the risk of any recurrence (HR 0.99, 95% CI 0.73–1.34, P = 0.09) and there was no evidence for survival being different in men who underwent NSRP to those who underwent non‐NSRP (HR 0.65, 95% CI 0.39–1.08). There was also no evidence for the cancer‐specific survival (HR 0.56, 95% CI 0.29–1.11) or progression‐free survival (HR 0.99, 95% CI 0.73–1.34) being different between the groups. Conclusion: In patients with high‐risk PCa, NSRP can be attempted without compromising long‐term oncological outcomes provided a comprehensive assessment of objective (e.g., T Stage) and subjective (e.g., intraoperative appraisal of tissue planes) criteria are conducted. [ABSTRACT FROM AUTHOR]

The objective of the European Association of Urology guidelines is to provide practical evidence-based recommendations and consensus statements on the clinical management of urological conditions, with a focus on diagnosis and treatment. In this context the summary of the 2023 guideline on muscle-invasive and metastatic bladder cancer provides updated information on the diagnosis and treatment of this disease for incorporation in clinical practice. We present an overview of the updated 2023 European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. A broad and comprehensive scoping exercise covering all areas of the MMIBC guidelines has been performed annually since 2017. Searches cover the Medline, EMBASE, and Cochrane Libraries databases for yearly guideline updates. A level of evidence and strength of recommendation are assigned. The evidence cutoff date for the 2023 MIBC guidelines was May 4, 2022. Patients should be counselled regarding risk factors for bladder cancer. Pathologists should describe tumour and lymph nodes in detail, including the presence of histological subtypes. The importance of the presence or absence of urothelial carcinoma (UC) in the prostatic urethra is emphasised. Magnetic resonance imaging (MRI) of the bladder is superior to computed tomography (CT) for disease staging, specifically in differentiating T1 from T2 disease, and may lead to a change in treatment approach in patients at high risk of an invasive tumour. Imaging of the upper urinary tract, lymph nodes, and distant metastasis is performed with CT or MRI; the additional value of flurodeoxyglucose positron emission tomography/CT still needs to be determined. Frail and comorbid patients should be evaluated by a multidisciplinary team. Postoperative histology remains the most important prognostic variable, while circulating tumour DNA appears to be an interesting predictive marker. Neoadjuvant systemic therapy remains cisplatin-based. In motivated and selected women and men, sexual organ–preserving cystectomy results in better functional outcomes without compromising oncological outcomes. Robotic and open cystectomy have comparable outcomes and should be combined with (extended) lymph node dissection. The diversion type is an individual choice after taking patient and tumour characteristics into account. Radical cystectomy remains a highly complex procedure with considerable morbidity and risk of mortality, although lower rates are observed for higher hospital volumes (>20 cases/yr). With proper patient selection, trimodal therapy (chemoradiation) has comparable outcomes to radical cystectomy. Adjuvant chemotherapy after surgery improves disease-specific survival and overall survival (OS) in patients with high-risk disease who did not receive neoadjuvant treatment, and is strongly recommended. There is a weak recommendation for adjuvant nivolumab, as OS data are not yet available. Health-related quality of life should be assessed using validated questionnaires at baseline and after treatment. Surveillance is needed to monitor for recurrent cancer and functional outcomes. Recurrences detected on follow-up seem to have better prognosis than symptomatic recurrences. This summary of the 2023 EAU guidelines provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. The European Association of Urology guidelines panel on muscle-invasive and metastatic bladder cancer has released an updated version of the guideline containing information on diagnosis and treatment of this disease. Recommendations are based on studies published up to May 4, 2022. Surgical removal of the bladder and bladder preservation are discussed, as well as updates on the use of chemotherapy and immunotherapy in localised and metastatic disease. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the impact of lymphovascular invasion at the time of prostatectomy on oncological outcomes in patients with prostate cancer. We found that the presence of lymphovascular invasion at the time of radical prostatectomy is associated with aggressive prostate cancer disease features and is an indicator of poor oncological prognosis. Therefore, lymphovascular invasion status could be used as a factor to identify patients that have underlying disseminated disease and may benefit from systemic treatment intensification, especially those with high-risk disease. Further prospective studies need to be conducted to validate these findings. Lymphovascular invasion, whereby tumour cells or cell clusters are identified in the lumen of lymphatic or blood vessels, is thought to be an essential step in disease dissemination. It has been established as an independent negative prognostic indicator in a range of cancers. We therefore aimed to assess the impact of lymphovascular invasion at the time of prostatectomy on oncological outcomes. We performed a multicentre, retrospective cohort study of 3495 men who underwent radical prostatectomy for localised prostate cancer. Only men with negative preoperative staging were included. We assessed the relationship between lymphovascular invasion and adverse pathological features using multivariable logistic regression models. Kaplan–Meier curves and Cox proportional hazard models were created to evaluate the impact of lymphovascular invasion on oncological outcomes. Lymphovascular invasion was identified in 19% (n = 653) of men undergoing prostatectomy. There was an increased incidence of lymphovascular invasion-positive disease in men with high International Society of Urological Pathology (ISUP) grade and non-organ-confined disease (p < 0.01). The presence of lymphovascular invasion significantly increased the likelihood of pathological node-positive disease on multivariable logistic regression analysis (OR 15, 95%CI 9.7–23.6). The presence of lymphovascular invasion at radical prostatectomy significantly increased the risk of biochemical recurrence (HR 2.0, 95%CI 1.6–2.4). Furthermore, lymphovascular invasion significantly increased the risk of metastasis in the whole cohort (HR 2.2, 95%CI 1.6–3.0). The same relationship was seen across D'Amico risk groups. The presence of lymphovascular invasion at the time of radical prostatectomy is associated with aggressive prostate cancer disease features and is an indicator of poor oncological prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the functional and oncological outcomes of low and intermediate risk compared to high risk prostate cancer patients undergoing radical prostatectomy with attempted neurovascular bundle preservation. We found that satisfactory urinary continence and erectile function recovery is possible without compromising oncological outcomes. Therefore, preservation of the neurovascular bundle should be considered in carefully selected patients with high risk disease. Future studies should develop risk stratification tools to identify which high risk prostate cancer cases are suitable for nerve sparing. Nerve sparing (NS) is a surgical technique to optimize functional outcomes of radical prostatectomy (RP). However, it is not recommended in high risk (HR) cases because of the risk of a positive surgical margin that may increase the risk of cancer recurrence. In the last two decades there has been a change of perspective to the effect that in well-selected cases NS could be an oncologically safe option with better functional outcomes. Therefore, we aim to compare the functional outcomes and oncological safety of NS during RP in men with HR disease. A total of 1340 patients were included in this analysis, of which 12% (n = 158) underwent non-NSRP and 39% (n = 516) and 50% (n = 666) uni- and bilateral NSRP, respectively. We calculated a propensity score and used inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of Pca patients undergoing non-NSRP and those having uni- and bilateral NSRP, respectively. NS improved functional outcomes; after IPTW, only 3% of patients having non-NSRP reached complete erectile function recovery (without erectile aid) at 24 months, whereas 22% reached erectile function recovery (with erectile aid), while 87% were continent. Unilateral NS increased the probability of functional recovery in all outcomes (OR 1.1 or 1.2, respectively), bilateral NS slightly more so (OR 1.1 to 1.4). NSRP did not impact the risk of any recurrence (HR 0.99, 95%CI 0.73–1.34, p = 0.09), and there was no difference in survival for men who underwent NSRP (HR 0.65, 95%CI 0.39–1.08). There was no difference in cancer-specific survival (0.56, 95%CI 0.29–1.11). Our study found that NSRP significantly improved functional outcomes and can be safely performed in carefully selected patients with HR-PCa without compromising long term oncological outcomes. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group," by Peter Grimm and colleagues in the 2012 issue is presented.

Background:A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking. Methods:In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP) with general anesthesia combined with intra- and postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine analgesia (n=81) were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death. Results:The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001). Conclusions:General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs. [ABSTRACT FROM AUTHOR]

Abstract: Context: Guidelines for the management of pT1G3 bladder cancer (BCa) are based on different and specific levels of evidence. Objective: This review examines the clinical evidence for the management of pT1G3 BCa with an organ-preserving approach and with radical cystectomy (RC) and the risk factors involved. Evidence acquisition: Data were acquired from the recent literature. Evidence synthesis: The tumour biology and outcome of T1G3 bladder tumours is variable. Organ preservation is feasible in solitary tumours, with few risk factors after a second transurethral resection of bladder tumour and no evidence of residual disease. Other patients should be offered RC unless they are not fit to undergo major surgery. Risk factors include concomitant carcinoma in situ, tumour multifocality, tumour diameter >3cm, and depth of lamina propria infiltration. Conclusions: Treatment outcome may be improved through risk stratification and patient selection. In patients fit for major surgery showing multiple risk factors and at high risk for progression, RC with extended pelvic lymph node dissection should be offered. In patients with solitary tumours presenting with few risk factors and in patients not fit for major surgery, a conservative organ-preserving approach is acceptable. This risk constellation must be kept in mind for adequate counselling of patients with T1G3 disease in our everyday practice. [Copyright &y& Elsevier]

Objectives: To evaluate the usefulness of radiological re‐staging after two and four cycles of neoadjuvant chemotherapy (NAC), the impact of re‐staging on further patient management, and the correlation between clinical and final pathological tumour stage at radical cystectomy (RC). Patients and Methods: We conducted a longitudinal, single‐centre, cohort study of prospectively collected consecutive patients who underwent NAC and RC for urothelial muscle‐invasive bladder cancer between July 2001 and December 2017. Patients underwent repeated computed tomography scans for re‐staging after two cycles of NAC and after completion of NAC before RC. Results: Of 180 patients, 110 had ≥four cycles of NAC and had complete imaging available. In the entire cohort, further patient management was only changed in 2/180 patients (1.1%) after two cycles of NAC based on radiological findings. Patients who were stable after two cycles but then downstaged after at least four cycles of NAC had a similarly lowered risk of death (hazard ratio [HR] 0.53). Only one patient downstaged after two cycles was subsequently upstaged after four cycles. Clinical downstaging was observed in 51 patients (46%), 55 patients (50%) had no change in clinical stage and four patients (3.6%) were clinically upstaged. Patients clinically downstaged after four cycles of NAC had a lower risk of death (HR 0.49, 95% confidence interval 0.25–0.94; P = 0.033) compared to those with no change or upstaged after completion of NAC. Conclusions: Re‐staging of muscle‐invasive bladder cancer after two cycles of NAC offers little additional information, rarely changes patient management, and may therefore be omitted, whereas re‐staging after completion of NAC by CT is a strong predictor of overall survival. [ABSTRACT FROM AUTHOR]

Objective: To evaluate cognitive trajectories after radical cystectomy and their impact on surgical outcomes, including urinary continence.Materials and Methods: Ninety patients received cognitive testing using the Mini Mental State Examination before open radical cystectomy as well as 3 days and 2 weeks after surgery. Based on the Mini Mental State Examination changes ≥3 points between the three time points, five cognitive trajectories emerged (stable cognition, persistent or transient deterioration, or persistent or transient improvement). Surgical outcomes were assessed 90 days, 6 months, and 1 year postoperatively.Results: Mean age was 67.9 ± 9.3 years (range 40-88 years). Sixty-six patients (73.3%) had stable cognition, 9 patients (10.0%) had persistent deterioration and 7 patients (7.8%) had transient deterioration, 5 patients (5.6%) had persistent improvement and 3 patients (3.3%) had transient improvement. An impaired preoperative cognition was the only significant risk factor of short-term cognitive deterioration (odds ratio adjusted for age and sex 9.4, 95% confidence interval 1.6-56.5, P = .014). Cognition showed no associations with 1-year mortality, 90-day complication rate, cancer progression, or duration of in-hospital stay. Patients with transient or persistent cognitive deterioration had an increased risk for nighttime incontinence (odds ratio adjusted for age and sex 5.1, 95% confidence interval 1.1-22.4, P = .032).Conclusion: In this study, the majority of patients showed stable cognition after major abdominopelvic surgery. Cognitive deterioration occurred in a small subgroup of patients, and an impaired preoperative cognition was the only significant risk factor. Postoperative cognitive deterioration was associated with nighttime incontinence. [ABSTRACT FROM AUTHOR]

Their results demonstrate the clonal origin of tumours in the upper and lower urinary tract that arise sequentially in individual patients with a history of both tumours [27]. Abbreviations OBS orthotopic bladder substitute RC radical cystectomy UC urothelial carcinoma Radical cystectomy (RC) with bilateral excision of the pelvic lymph nodes is the first-line treatment for localized muscle-invasive carcinoma of the urinary bladder [1], while ileal orthotopic bladder substitute (OBS) has become the preferred method of continent urinary diversion. In our patient, recurrent transurethral resection of the tumour in the ileal OBS was a therapeutic option on several occasions, thus delaying resection of the continent urinary diversion. [Extracted from the article]

Objectives To prospectively evaluate the outcome of combined microwave-induced bladder wall hyperthermia and intravesical mitomycin C instillation (thermochemotherapy) in patients with recurrent non-muscle-invasive bladder cancer. Methods Between 2003 and 2009, 21 patients (median age 70 years, range 35-95 years) with recurrent non-muscle-invasive bladder cancer ( pTaG1-2 n = 9; pTaG3 n = 3; pT1 n = 9; concurrent p Tis n = 8) were prospectively enrolled. Of 21 patients, 15 (71%) had received previous intravesical instillations with bacillus Calmette- Guérin, mitomycin C and/or farmorubicin. Thermochemotherapy using the Synergo system was carried out in 11 of 21 patients (52%) with curative intent, and in 10 of 21 patients (48%) as prophylaxis against recurrence. Results The median number of thermochemotherapy cycles per patient was six (range 1-12). Adverse effects were frequent and severe: urinary urgency/frequency in 11 of 21 patients (52%), pain in eight of 21 patients (38%) and gross hematuria in five of 21 patients (24%). In eight of 21 patients (38%), thermochemotherapy had to be abandoned because of the severity of the adverse effects (pain in 3/8, severe bladder spasms in 2/8, allergic reaction in 2/8, urethral perforation in 1/8). Overall, six of 21 patients (29%) remained free of tumor after a median follow up of 50 months (range 1-120), six of 21 patients (29%) had to undergo cystectomy because of multifocal recurrences or cancer progression and seven of 21 patients (33%) died (2/7 of metastatic disease, 5/7 of non-cancer related causes). Conclusions Given the high rate of severe side-effects leading to treatment discontinuation, as well as the limited tumor response, thermochemotherapy should be offered only in highly selected cases of recurrent non-muscle-invasive bladder cancer. [ABSTRACT FROM AUTHOR]

Background: Open radical cystectomy (ORC) is associated with substantial blood loss and a high incidence of perioperative blood transfusions. Strategies to reduce blood loss and blood transfusion are warranted. Objective: To determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringer's maleate solution can reduce blood loss and the need for blood transfusion. Design, setting, and participants: This was a double-blind, randomised, parallel-group, single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion (UD). Exclusion criteria were severe hepatic or renal dysfunction, congestive heart failure, and contraindications to epidural analgesia. Intervention: Patients were randomly allocated to continuous norepinephrine administration starting with 2 µg/kg per hour combined with 1 ml/kg per hour until the bladder was removed, then to 3 ml/kg per hour of Ringer's maleate solution (norepinephrine/low-volume group) or 6 ml/kg per hour of Ringer's maleate solution throughout surgery (control group). Outcome measurements and statistical analysis: Intraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed. Data were analysed using nonparametric statistical models. Results and limitations: Total median blood loss was 800 ml (range: 300-1700) in the norepinephrine/low-volume group versus 1200 ml (range: 400-2800) in the control group (p < 0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%) required an average of 1.8 U (±0.8) of packed red blood cells (PRBCs). In the control group, 50 of 83 patients (60%) required an average of 2.9 U (±2.1) of PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI], 0.38-0.77; p = 0.0006). The absolute reduction in transfusion rate throughout hospitalisation was 28% (95% CI, 12-45). In this study, surgery was performed by three high-volume surgeons using a standardised technique, so whether these significant results are reproducible in other centres needs to be shown. Conclusions: Continuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss, the rate of blood transfusions, and the number of PRBC units required per patient undergoing ORC with UD. Take Home Message: Intraoperative continuous norepinephrine administration combined with restrictive deferred hydration significantly reduces intraoperative blood loss and the rate of blood transfusions in patients undergoing open radical cystectomy with urinary diversion. [ABSTRACT FROM AUTHOR]

During disease progression from primary towards metastatic prostate cancer (PCa), and in particular bone metastases, the tumor microenvironment (TME) evolves in parallel with the cancer clones, altering extracellular matrix composition (ECM), vasculature architecture, and recruiting specialized tumor-supporting cells that favor tumor spread and colonization at distant sites. We introduce the clinical profile of advanced metastatic PCa in terms of common genetic alterations. Findings from recently developed models of PCa metastatic spread are discussed, focusing mainly on the role of the TME (mainly matrix and fibroblast cell types), at distinct stages: premetastatic niche orchestrated by the primary tumor towards the metastatic site and bone metastasis. We report evidence of premetastatic niche formation, such as the mechanisms of distant site conditioning by extracellular vesicles, chemokines and other tumor-derived mechanisms, including altered cancer cell-ECM interactions. Furthermore, evidence supporting the similarities of stroma alterations among the primary PCa and bone metastasis, and contribution of TME to androgen deprivation therapy resistance are also discussed. We summarize the available bone metastasis transgenic mouse models of PCa from a perspective of pro-metastatic TME alterations during disease progression and give an update on the current diagnostic and therapeutic radiological strategies for bone metastasis clinical management. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anesthetics and neuraxial anesthesia commonly result in vasodilation/hypotension. Norepinephrine counteracts this effect and thus allows for decreased intraoperative hydration. The authors investigated whether this approach could result in reduced postoperative complication rate. METHODS: In this single-center, double-blind, randomized, superiority trial, 166 patients undergoing radical cystectomy and urinary diversion were equally allocated to receive 1 ml·kg·h of balanced Ringer's solution until the end of cystectomy and then 3 ml·kg·h until the end of surgery combined with preemptive norepinephrine infusion at an initial rate of 2 ug·kg·h (low-volume group; n = 83) or 6 ml·kg·h of balanced Ringer's solution throughout surgery (control group; n = 83). Primary outcome was the in-hospital complication rate. Secondary outcomes were hospitalization time, and 90-day mortality. RESULTS: In-hospital complications occurred in 43 of 83 patients (52%) in the low-volume group and in 61 of 83 (73%) in the control group (relative risk, 0.70; 95% CI, 0.55-0.88; P = 0.006). The rates of gastrointestinal and cardiac complications were lower in the low-volume group than in the control group (5 [6%] vs. 31 [37%]; relative risk, 0.16; 95% CI, 0.07-0.39; P < 0.0001 and 17 [20%] vs. 39 [48%], relative risk, 0.43; 95% CI, 0.26-0.60; P = 0.0003, respectively). The median hospitalization time was 15 days [range, 11, 27d] in the low-volume group and 17 days [11, 95d] in the control group (P = 0.02). The 90-day mortality was 0% in the low-volume group and 4.8% in the control group (P = 0.12). CONCLUSION: A restrictive-deferred hydration combined with preemptive norepinephrine infusion during radical cystectomy and urinary diversion significantly reduced the postoperative complication rate and hospitalization time. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? The Endo Sew® prototype was first tested in a porcine model several years ago. The investigators found it both simple to master and reliable, its greatest advantage being a 2.4-fold time saving compared with straight laparoscopic suturing. In addition to that publication, there is a single case report describing the performance of an open EndoSew® suture to close parts (16 cm) of an ileal neobladder. The time for suturing the 16 cm ileum was 25 min, which is in line with our experience. The knowledge on this subject is limited to these two publications., We report on the first consecutive series of ileal conduits performed in humans using the novel prototype sewing device Endo Sew®. The study shows that the beginning and the end of the suture process represent the critical procedural steps. It also shows that, overall, the prototype sewing machine has the potential to facilitate the intracorporeal suturing required in reconstructive urology for construction of urinary diversions., Objective To evaluate the feasibility and safety of the novel prototype sewing device Endo Sew® in placing an extracorporeal resorbable running suture for ileal conduits., Patients and Methods We conducted a prospective single-centre pilot study of 10 consecutive patients undergoing ileal conduit, in whom the proximal end of the ileal conduit was closed extracorporeally using an Endo Sew® running suture., The primary endpoint was the safety of the device and the feasibility of the sewing procedure which was defined as a complete watertight running suture line accomplished by EndoSew® only . Watertightness was assessed using methylene blue intraoperatively and by loopography on postoperative days 7 and 14., Secondary endpoints were the time requirements and complications ≤30 days after surgery., Results A complete EndoSew® running suture was feasible in nine patients; the suture had to be abandoned in one patient because of mechanical failure., In three patients, two additional single freehand stitches were needed to anchor the thread and to seal tiny leaks. Consequently, all suture lines in 6/10 patients were watertight with EndoSew® suturing alone and in 10/10 patients after additional freehand stitches., The median (range) sewing time was 5.5 (3-10) min and the median (range) suture length was 4.5 (2-5.5) cm., There were no suture-related complications., Conclusions The EndoSew® procedure is both feasible and safe., After additional freehand stitches in four patients all sutures were watertight., With further technical refinements, Endo Sew® has the potential to facilitate the intracorporeal construction of urinary diversions. [ABSTRACT FROM AUTHOR]

Patients with treatment-naïve metastatic urothelial carcinoma are grouped according to platinum eligibility based on clear definitions. In general, first-line treatment consists of platinum-based chemotherapy in which cisplatin is to be preferred to carboplatin. Patients who are cisplatin ineligible but carboplatin eligible should receive carboplatin-gemcitabine combination chemotherapy. In case of positive programmed death ligand 1 (PD-L1) status, treatment with checkpoint inhibitors (atezolizumab or pembrolizumab) could be an alternative option. Patients unfit for both cisplatin and carboplatin (platinum unfit) can be considered for immunotherapy (U.S. Food and Drug Administration approved irrespective of PD-L1 status and European Medicines Agency approved only for PD-L1 positive) or can receive best supportive care. Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients. [ABSTRACT FROM AUTHOR]

Abstract: Current conventional cross-sectional imaging techniques, such as contrast-enhanced computed tomography and magnetic resonance imaging (MRI), are largely inaccurate in detecting local recurrence after radical prostatectomy. We report on five patients with biochemical recurrence after radical retropubic prostatectomy and pelvic lymph node dissection for whom local recurrence could only be detected with diffusion-weighted (DW) MRI. Prior to DW-MRI, all patients had negative digital rectal examinations, negative or equivocal conventional cross-sectional imaging, and negative bone scans. All suspicious lesions on DW-MRI imaging were histologically proved to be local recurrences of prostate cancer after either transrectal ultrasound–guided or transurethral biopsy. These results should encourage other centres to test our findings. [Copyright &y& Elsevier]

Seiler R, von Gunten M, Thalmann G N & Fleischmann A (2011) Histopathology , 571-578 To evaluate risk factors in lymph node-positive bladder cancer. Lymph node-positive bladder cancer patients ( n = 162), preoperatively staged N0M0, underwent cystectomy and standardized extended lymphadenectomy. Five-year overall survival of the cohort was 33%. In univariate analysis, tumour stage ( P < 0.006), extracapsular extension of lymph node metastases ( P < 0.001), total diameter of metastases ( P < 0.04) and lymph node stage ( P < 0.03) were significantly correlated with overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS). On multivariate analysis, only extracapsular extension (OS, P < 0.002; DSS, P < 0.02; RFS, P = 0.058) and primary tumour stage (OS, P = 0.058; DSS, P < 0.02; RFS, P < 0.02) added independent prognostic information. Extracapsular extension of lymph node metastases did not correlate with a specific recurrence pattern; patients with organ-confined tumours (pT1/2) never had pelvic relapse. Extracapsular extension of lymph node metastases but not lymph node tumour burden adds independent prognostic information in lymph node-positive bladder cancer. These biological differences in lymph node-positive bladder cancer are not reflected in the sixth, and challenge future, TNM classification. [ABSTRACT FROM AUTHOR]

Abstract: Background: Conflicting results exist regarding the value of an extended pelvic lymph node dissection (PLND) in node-positive patients undergoing radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. Objective: To assess the long-term outcome in node-positive patients who underwent extended PLND followed by RRP. Design, setting, and participants: A consecutive series of 122 node positive patients with negative preoperative staging examinations, no neoadjuvant hormonal or radiotherapy, and who underwent extended PLND (≥10 lymph nodes in the surgical specimen) followed by RRP were analyzed. None of the patients received immediate androgen deprivation therapy (ADT). Intervention: All patients underwent extended PLND followed by RRP. Measurements: Biochemical recurrence-free survival, cancer-specific, and overall survival were assessed using the Kaplan-Meier technique. Results and limitations: Median prostate-specific antigen (PSA) was 16ng/ml. At pathological examination 76% of the 122 patients had pT3–pT4 tumours, 50% seminal vesicle infiltration. A median of 22 nodes were removed per patient. Median cancer-specific survival at 5 and 10 yr was 84.5% and 60.1%, respectively. In patients with ≤2 or ≥3 positive nodes removed, median cancer-specific survival at 10 yr was 78.6% and 33.4%, respectively (p <0.001). After a median period of 33 mo, 61 of the 122 patients (50%) received ADT, particularly those (69%) with ≥3 positive nodes removed. This retrospective study includes a significant percentage of patients with high tumour burden, and therefore may not reflect current patient series. Conclusions: Patients with ≤2 positive nodes detected after extended PLND followed by RRP had good long-term results and should not be denied treatment with curative intent. In contrast, prognosis was poor in patients with ≥3 positive nodes, despite extended PLND and despite ADT in 69% of patients. [Copyright &y& Elsevier]

OBJECTIVE To determine the long-term oncological outcome of patients with primary transitional cell carcinoma (TCC) of the distal ureter electively treated with either kidney-sparing surgery (KSS) or radical nephroureterectomy (RNU) in a retrospective, non-randomized, single-centre study. PATIENTS AND METHODS Of 43 consecutive patients with a primary solitary distal ureter TCC, 19 had KSS, consisting of distal ureter resection with bladder cuff excision and ureter reimplantation, and 24 had RNU with bladder cuff excision. RESULTS The median (range) age at surgery was 69 (31–86) years for the KSS group and 73 (59–87) years for the RNU group, patients in the latter having worse hydronephrotic kidneys. The median (range) follow-up was 58 (3–260) months. A recurrent bladder tumour was diagnosed after a median of 15 months in five of the 19 patients treated by KSS and after a median of 5.5 months in eight of the 24 treated by RNU. Five of the 19 patients treated by KSS and six of the 24 treated by RNU died from metastatic disease despite chemotherapy. Recurrence-free, cancer-specific and overall survival were comparable in the two groups. In two patients (11%) treated by KSS an ipsilateral upper urinary tract TCC recurred after 42 and 105 months, respectively. CONCLUSION Treatment by distal ureteric resection is feasible in patients with primary TCC of the distal ureter. The long-term oncological outcome seems to be comparable with that of patients treated by RNU. Furthermore, kidney preservation is advantageous if adjuvant or salvage chemotherapy is required. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Controversy persists concerning the role of pelvic lymph node dissection (PLND) in patients with preoperative PSA values <10ng/ml undergoing treatment for prostate cancer with a curative intent. The aim of this study was to determine the incidence of lymph node metastasis in this subgroup of patients. Methods: Patients with clinically localized prostate cancer and a serum PSA<10ng/ml, without neoadjuvant hormonal or radiotherapy, with negative staging examinations who underwent radical retropubic prostatectomy with bilateral extended PLND and with ≥10 lymph nodes detected by the pathologist in the surgical specimen, were included in the study. Results: A total of 231 patients with a median serum PSA of 6.7ng/ml (range 0.4–9.98) and a median age of 62 years (range 44–76) were evaluated. A median of 20 (range 10–72) nodes were removed per patient. Positive nodes were found in 26 of 231 patients (11%), the majority of which (81%) had a Gleason score ≥7 in the surgical specimen. Of the patients with a Gleason score ≥7 in the prostatectomy specimen 25% had positive nodes, whereas only 3% with a Gleason score ≤6 were node positive. Conclusions: The incidence of positive nodes in patients with clinically localized prostate cancer, a serum PSA<10ng/ml and a Gleason score ≥7 in the prostatectomy specimen was 25% after extended PLND. It seems that in this patient group extended PLND, including removal of nodes along the internal iliac vessels, is warranted. [Copyright &y& Elsevier]

This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted. Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non–muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in "fit" patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1–negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/. This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease. Radical cystectomy with urinary diversion remains the mainstay of managing muscle-invasive bladder cancer (MIBC). The use of neoadjuvant chemotherapy (NAC) has improved overall survival rates, but selection of patients who will benefit most from NAC remains challenging. In case bladder-preserving strategies are considered, patient stratification according to their risk profile is imperative and management should be discussed in a multidisciplinary team. As yet, there are no validated prognostic molecular markers to guide the clinical management of MIBC. In a metastatic setting, cisplatin-based chemotherapy remains the first choice in fit patients. In unfit patients, based on interim results from two on-going clinical trials, first-line treatment with pembrolizumab or atezolizumab for urothelial cancer is restricted to Programmed Death Ligand 1-positive patients only. [ABSTRACT FROM AUTHOR]

Bladder cancer is a heterogeneous disease that is not depicted by current classification systems. It was originally classified into non-muscle invasive and muscle invasive. However, clinically and genetically variable tumors are summarized within both classes. A definition of three groups may better account for the divergence in prognosis and probably also choice of treatment. The first group represents mostly non-invasive tumors that reoccur but do not progress. Contrarily, the second group represent non-muscle invasive tumors that likely progress to the third group, the muscle invasive tumors. High throughput tumor profiling improved our understanding of the biology of bladder cancer. It allows the identification of molecular subtypes, at least three for non-muscle invasive bladder cancer (Class I, Class II and Class III) and six for muscle-invasive bladder cancer (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous and neuroendocrine-like) with distinct clinical and molecular phenotypes. Molecular subtypes can be potentially used to predict the response to treatment (e.g., neoadjuvant chemotherapy and immune checkpoint inhibitors). Moreover, they may allow to characterize the evolution of bladder cancer through different pathways. However, to move towards precision medicine, the understanding of the biological meaning of these molecular subtypes and differences in the composition of cell subpopulations will be mandatory. [ABSTRACT FROM AUTHOR]

Objective: Analysis of treatment success regarding oncological recurrence rate between standard and dose escalation focal high-intensity focused ultrasound (HIFU) of prostate cancer. Materials and Methods: In this analysis of our prospectively maintained HIFU (Sonablate® 500) database, 598 patients were identified who underwent a focal HIFU (Sonablate 500) between March 2007 and November 2016. Follow-up occurred with 3-monthly clinic visits and prostate specific antigen (PSA) testing in the first year. Thereafter, PSA was measured 6-monthly or annually at least. Routine and for-cause multiparametric MRI (mpMRI) was conducted with biopsy for MRI suspicion of recurrence. Treatments were delivered in a quadrant or hemiablation fashion depending on the gland volume as well as tumor volume and location. Before mid-2015, standard focal HIFU was used (two HIFU blocks); after this date, some urologists conducted dose escalation focal HIFU (three overlapping HIFU blocks). Propensity matching was used to ensure two matched groups, leading to 162 cases for this analysis. Treatment failure was defined by any secondary treatment (systemic therapy, cryotherapy, radiotherapy, prostatectomy, or further HIFU), metastasis from prostate cancer without further treatment, tumor recurrence with Gleason score ≥7 (≥3 + 4) on prostate biopsy without further treatment, or prostate cancer-related mortality. Complications and side-effects were also compared. Results: Median age was 64.5 years (interquartile range [IQR] 60–73.5) in the standard focal-HIFU group and 64.5 years (IQR 60–69) in the dose-escalation group. Median prostate volume was 37 mL (IQR 17–103) in the standard group and 47.5 mL (IQR 19–121) in the dose-escalation group. As tumor volume on mpMRI and Gleason score were major matching criteria, these were identical with 0.43 mL (IQR 0.05–2.5) and Gleason 3 + 3 = 6 in 1 out of 32 (3%), 3 + 4 = 7 in 27 out of 32 (84%), and 4 + 3 = 7 in 4 out of 32 (13%). Recurrence in treated areas was found in 10 out of 32 (31%) when standard treatment zones were applied, and in 6 out of 32 (19%) of dose-escalation focal HIFU (p = 0.007). Conclusion: This exploratory study shows that dose escalation focal HIFU may achieve higher rates of disease control compared with standard focal HIFU. Further prospective comparative studies are needed. [ABSTRACT FROM AUTHOR]