[Cisplatin-based chemotherapy in muscle-invasive bladder cancer: soon outdated ?]

For more than 30 years, cisplatin-based neoadjuvant chemotherapy (NAC) has been administered to patients with muscle-invasive bladder cancer (MIBC). However, the benefit is modest. With the advent of modern immunotherapies, new therapeutic strategies are also opening up to bladder cancer. Unfortunately, the initial results in the neoadjuvant context show a response rate of only 20-35 %. Other therapeutic strategies, such as Pan-FGFR inhibitors, do not show better response. Due to the high genetic variability of bladder cancer, a « one drug fits all » concept is not an ideal solution. Patient selection based on the probability of response appears to be a promising strategy to improve this modest benefit of each treatment. In this context, the NAC will also continue to play an important role

[Instillation therapies for urothelial carcinoma of the upper urinary tract].

Traditionally, urothelial carcinoma of the upper urinary tract was a clear indication for radical nephroureterectomy with bladder cuff excision. It has been shown that in well-selected patients and depending on tumor stage, a kidney-sparing approach can be pursued with good oncological outcome and equivalent to the radical approach. The prevention of local and bladder recurrences is an important factor. Instillation therapies with bacillus Calmette-Guérin and/or mitomycin C have been successfully used to this end. Due to the low incidence of upper tract urothelial cancer and due to the usually retrospective nature of existing literature, however, data is limited. In this article, we provide a review of the indication, technical execution and results of instillation therapies of the upper urinary tract

Secondary intervention due to symptomatic ureteral stones is not necessary in the majority of patients after previous stenting

Introduction and Objective Over the past 20 years, ureteroscopy (URS) has become one of the most popular treatment options for patients with ureterolithiasis. While prestenting is usually not necessary if the ureteral stones is <1 cm, some clinical situations (e.g. obstructive pyelonephritis) require stent placement for a short period. While the stent dilates the ureter, thus facilitating spontaneous stone passage, the question arises whether secondary intervention is necessary at all. We thus evaluated whether our institutional approach of removing the ureteral stent the day before secondary intervention in local anesthesia can spare the patient this intervention. Methods: Retrospective analysis of 216 patients who had previously been stented due to a symptomatic ureteral stone and who were scheduled for secondary intervention from 01/2013 to 01/2018 at our institution. The stent was removed under local anaesthesia. Patients were told to filter their urine overnight. Spontaneous stone passage or persistence of the stone was documented either by presenting the filtered stone and/or radiologically. To evaluate potential predictors for spontaneous stone passage (stone size, location, composition, stent dwell time, patient age and sex), a multivariable logistic regression was performed. Results: Median stone size was 5 mm (IQR:4-6). 26% of stones were located in the proximal, 25% in the mid-, and 49% in the distal ureter. 129/216 (60%) patients had spontaneous stone passage after a median stent dwell time of 4 weeks (IQR:3-5): 72/129 (56%) before and 57/129 (44%) within 24 hours after stent removal. In only 87/216 (40%) pre-stented patients a secondary intervention was necessary. Multivariable logistic regression analysis showed a significant association between spontaneous stone passage and stone size (OR:0.67, 95%CI: 0.55-0.83; p<0.001), distal stone location (OR:2.17, 95%CI: 1.01-4.67; p=0.049) and stent dwell time (OR:1.20; 95%CI: 1.03-1.40; p=0.02). Conclusions: The majority (60%) of ureteral stones passed spontaneously after senting, especially if they were small and located in the distal ureter; 44% of these stones passed within 24 hours after stent removal. Thus, a stent should be removed at least one day before secondary intervention in order to avoid unnecessary surgery. Characters (not including spaces): 2091 Topic: Stone disease – surgical therapy Key words: ureteral calculi, stents, ureteroscopy Source of funding: Non

Routine Preoperative Bone Scintigraphy Has Limited Impact on the Management of Patients with Invasive Bladder Cancer.

BACKGROUND According to current guidelines, bone scintigraphy is not routinely indicated in patients with invasive bladder cancer prior to radical cystectomy unless specific symptoms are present. These guidelines, however, are based on sparse data of low quality. OBJECTIVE To assess the clinical impact of routine staging bone scintigraphy on further patient management. DESIGN, SETTING, AND PARTICIPANTS A retrospective, single-center study of 1287 consecutive patients, who were scheduled to undergo radical cystectomy due to invasive bladder cancer between January 2000 and December 2017, was conducted. All patients were prospectively followed up according to our institutional protocol. INTERVENTION Bone scintigraphy as staging imaging prior to radical cystectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary endpoint was the change in intended patient management. Secondary endpoints were the need for additional imaging, the diagnostic performance of baseline bone scintigraphy, and the association between clinical and radiological findings on bone metastases and survival. Logistic and Cox regression models were used for univariate and multivariate analyses. RESULTS AND LIMITATIONS Of 1287 patients scheduled for radical cystectomy, 1148 (89%) underwent bone scintigraphy as staging imaging. Overall, baseline bone scintigraphy led to a change in the intended management in 19/1148 (1.7%) patients. Additional imaging was performed in 44/1148 (4%) patients. Although positive bone scintigraphy findings were associated with the occurrence/development of bone metastases, the diagnostic performance of baseline bone scintigraphy was generally poor (positive predictive value, negative predictive value, sensitivity, and specificity were 56%, 89%, 27%, and 96%, respectively). Higher clinical tumor stage and the nonperformance of cystectomy had negative impacts on cancer-specific survival and overall survival, while positive bone scintigraphy was associated with worse cancer-specific survival. This study was limited by its retrospective nature and the lack of follow-up bone scintigraphy in all patients. CONCLUSIONS These results demonstrate the limited value of bone scintigraphy in the staging of invasive bladder cancer and do not support its routine use. PATIENT SUMMARY In this study, we looked at the clinical impact of bone scintigraphy on the diagnostics of patients with invasive bladder cancer. We found that routine staging bone scintigraphy had limited impact on further patient management. We conclude that bone scintigraphy should not be part of routine staging in patients with invasive bladder cancer

A treatment strategy to help select patients who may not need secondary intervention to remove symptomatic ureteral stones after previous stenting.

PURPOSE This study aimed at evaluating whether removal of the ureteral stent the day before scheduled secondary intervention facilitates spontaneous ureteral stone passage and thus can spare the pre-stented patient this surgery. METHODS Retrospective analysis of a single-centre consecutive series of 216 patients after previous stenting due to a symptomatic ureteral stone from 01/2013 to 01/2018. Indwelling stents were removed under local anaesthesia. Patients were told to filter their urine overnight. Multivariate analysis was performed to assess predictive factors for spontaneous stone passage. RESULTS 34% (74/216) of patients had spontaneous stone passage while the stent was indwelling. Of the remaining 142 patients, 41% (58/142) had spontaneous stone passage within 24 h after stent removal. Only 84/216 (39%) patients needed secondary intervention. Multivariate logistic regression analysis of all 216 patients showed a significant association between spontaneous stone passage and smaller stone size (p < 0.001), distal stone location (p = 0.046) and stent dwell time (p = 0.02). Predictive factors for spontaneous stone passage after stent removal were smaller size (p < 0.001), distal location (p = 0.001), and stone movement while the stent was indwelling (p = 0.016). A treatment strategy was established that helps select patients suitable for conservative management. CONCLUSIONS The majority (61%) of ureteral stones passed spontaneously after pre-stenting; 34% while the stent was indwelling, 27% within 24 h after stent removal. Besides distal stone location, stone size (< 6 mm) and stone movement (≥ 5 cm) while the stent is indwelling indicate patients who are likely to pass their ureteral stone spontaneously after stent removal. The treatment strategy (decision tree) presented here helps identify those patients. TRIAL REGISTRATION https://doi.org/10.1186/ISRCTN12112914

Seminal Vesical Sparing Cystectomy in Bladder Cancer Patients is Feasible with Good Functional Results without Impairing Oncological Outcomes: A Longitudinal Long-Term Propensity-Matched Single Center Study.

PURPOSE Seminal-vesicle-sparing radical-cystectomy has been reported to improve short-term functional-results without compromising oncological outcomes. However, there is still a lack of data on long-term outcomes after seminal-vesicle-sparing radical-cystectomy. The aim of this study was to compare oncological and functional outcomes in patients after seminal-vesicle-sparing vs nonseminal-vesicle-sparing radical-cystectomy. MATERIAL AND METHODS Oncological and functional outcomes of 470 consecutive patients after radical-cystectomy and orthotopic ileal reservoir from 2000 to 2017 were evaluated. They were stratified into 6 groups according to nerve-sparing and seminal-vesicle-sparing status as attempted during surgery: no-sparing at all (n=55), unilateral-nerve-sparing (n=159), bilateral-nerve-sparing (n=132), unilateral-seminal-vesicle-sparing and unilateral-nerve-sparing (n=30), unilateral-seminal-vesicle-sparing and bilateral-nerve-sparing (n=45), and bilateral seminal-vesicle-sparing (n=49) and used propensity modelling to adjust for preoperative differences. RESULTS Median follow-up among the entire cohort was 64months. Among the 6 groups, our analysis showed no difference in local recurrence-free survival (p=0.173). However, progression free, cancer-specific and overall survival were more favourable in patients with seminal-vesicle-sparing radical-cystectomy (p <0.001, p=0.006 and p <0.001, respectively). Proportions of patients with erectile function recovery were higher in the seminal-vesicle-sparing groups at all time points in all analyses, respectively, with pronounced earlier recovery in patients with bilateral-SVS. Importantly, patients with seminal-vesicle-sparing were significantly less in need of erectile aids to achieve erection and intercourse. Over the whole period, daytime urinary-continence was significantly better in the seminal-vesicle-sparing groups (OR 2.64 to 5.21). CONCLUSIONS In a highly selected group of patients, seminal-vesicle-sparing radical-cystectomy is oncologically safe and results in excellent functional outcomes that are reached at an earlier timepoint after surgery and remain superior over a longer period of time

Comparison of the Diagnostic Performance of Contrast-enhanced Ultrasound with That of Contrast-enhanced Computed Tomography and Contrast-enhanced Magnetic Resonance Imaging in the Evaluation of Renal Masses: A Systematic Review and Meta-analysis

Contrast-enhanced ultrasound (CEUS) has the potential to be a valuable alternative to contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMR), the current gold standards in characterisation of renal masses. To systematically review all available evidence on the qualitative diagnostic performance of CEUS versus that of CECT and CEMR in the evaluation of benign and malignant cystic and solid renal masses. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. After screening 1483 articles, six cohort studies and 10 descriptive studies were included. Pooling data from included studies with final diagnosis of benign or malignant renal masses by pathology showed a significant difference in the sensitivity of CEUS (0.96; 95% confidence interval [CI] 0.94-0.98) versus that of CECT (0.90; 95% CI 0.86-0.93). Pooling data from included studies with final diagnosis by pathology report or reaffirmed diagnosis by follow-up imaging without pathology report showed significant difference in the sensitivity of CEUS (0.98; 95% CI 0.94-1.0) versus that of CEMR (0.78; 95% CI 0.66-0.91). Preliminary data imply that CEUS may perform at least as well as or better than CECT and CEMR in the diagnosis of renal masses. However, the evidence base is limited, and more high-quality, well-designed, adequately powered, and sampled studies are needed to reach definitive conclusions. Early data suggest that contrast-enhanced ultrasound is a promising option for the evaluation of renal masses, but more reliable evidence is required

Complication reporting with the Bern Comprehensive Complication Index CCI after open radical prostatectomy: A longitudinal long-term single-center study.

OBJECTIVE To impartially optimize complication reporting in patients after open radical prostatectomy (ORP) and pelvic lymph node dissection (PLND) by adopting the modified Bern Comprehensive Complication Index (CCI). ORP and PLND are associated with relevant postoperative morbidity. The CCI-ranging from 0 (no complications) to 100 (death)-is a tool that aims to integrate all complications occuring within 90 days postoperatively weighted by severity in a single formula. METHODS In an observational single-center cohort, 90-day postoperative complications of 1,123 consecutive patients undergoing standardized ORP and PLND between 1996 and 2017 were evaluated. Prospectively collected complications were graded according to the Clavien-Dindo Classification. Grade I to II complications were defined as minor and grade IIIa to V as major. Finally, the recently developed modified Bern CCI using an exponential function, which transforms the sum of the weights into a value between 0 and 100 and the original CCI for each patient were extracted and compared. The correlation between the modified Bern and original CCI values was depicted graphically. RESULTS The complication rate was 42%, with 18% minor and 24% major complications. With the original CCI, the threshold of 100 was exceeded in 1 patient who had a maximal index value of 101 within 90d postoperatively. The maximal value of the Bern CCI was 97.5. Mean Bern and original CCI scores and standard deviations were 6.2 (11.3) and 7.6 (12.2) at 30 days, and 9.3 (13.9) and 10.7 (14.2) at 90 days. CONCLUSIONS The Bern CCI provides a more precise depiction of postoperative morbidity and represents the burden in patients with >1 complication after ORP and PLND more accurately than the original CCI allowing for a more reliable evaluation of quality of care and recovery. It therefore warrants consideration for standardized reporting of complications after ORP and PLND

Functional Results, Complications Associated with the Serosa-lined Tunnel, and Quality of Life with a Cross-folded Ileal Reservoir Combined with an Afferent Tubular Isoperistaltic Segment for Heterotopic Continent Urinary Diversion: An Observational Long-term Cohort Analysis.

BACKGROUND In patients who do not qualify for an orthotopic urinary diversion, for example, the urethra cannot be spared or is functionally impaired, a heterotopic continent cutaneous cross-folded ileal reservoir offers a good alternative. OBJECTIVE To describe the indication, surgical technique, and postoperative management, and to report the reservoir-related outcomes and complications associated with the serosa-lined tunnel. DESIGN, SETTING, AND PARTICIPANTS Perioperative outcomes of 118 consecutive patients after cystectomy and a heterotopic ileal reservoir adapted from the Studer bladder substitute technique, operated between 2000 and 2018, were evaluated. The catheterisable serosa-lined tunnel was constructed from the appendix (Mitrofanoff, n = 63), an ileal segment (Yang-Monti, n = 48), or a fallopian tube (n = 7). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Pre- and postoperative data until last follow-up appointment were entered prospectively in the departmental database. The chi-square test was used to compare proportions. RESULTS AND LIMITATIONS Median follow-up was 94 (interquartile range 36-152) mo. No peri- or postoperative mortality was observed within 90 d of surgery. Patient satisfaction was high in 77.5% and moderate in 16.9%. Overall, complications associated with the serosa-lined tunnel occurred in 52% (61/118) of patients. Stenosis of the continent outlet developed in 38% (45/118) of patients: 33/45 (75%) were simply dilated/incised at the outpatient clinic, of those 24% (8/33) required additional endoscopic dilatation. Of patients with stenosis of the continent outlet, 27% (12/45) needed open revision surgery. During follow-up, 8% (nine/118) of patients required revision of the serosa-lined tunnel due to incontinence. Twelve months postoperatively, 95% (92/97) patients were continent. A limitation is the retrospective analysis from prospectively assessed data. This could limit the generalisability of these findings, as selection bias cannot be excluded. CONCLUSIONS The heterotopic continent cutaneous cross-folded ileal reservoir achieves good functional results. Complications associated with the serosa-lined tunnel occur in about half of the patients but generally are easy to manage. As a result, patient satisfaction is high. PATIENT SUMMARY In patients who do not qualify for an orthotopic bladder substitute, a heterotopic continent cutaneous cross-folded ileal reservoir offers a viable alternative with good postoperative functional results and high patient satisfaction

Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in Patients With Non-Muscle Invasive Bladder Cancer and Previous Failure of Conventional BCG Therapy

Background: VPM1002BC is a modified mycobacterium Bacillus Calmette Guérin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC). The genetic modifications are expected to result in better immunogenicity and less side effects. We report on patient safety and immunology of the first intravesical application of VPM1002BC in human. Methods: Six patients with BCG failure received a treatment of 6 weekly instillations with VPM1002BC. Patients were monitored for adverse events (AE), excretion of VPM1002BC and cytokines, respectively. Results: No DLT (dose limiting toxicity) occurred during the DLT-period. No grade ≥3 AEs occurred. Excretion of VPM1002BC in the urine was limited to less than 24 hours. Plasma levels of TNFα significantly increased after treatment and blood-derived CD4+ T cells stimulated with PPD demonstrated significantly increased intracellular GM-CSF and IFN expression. Conclusion: The intravesical application of VPM1002BC is safe and well tolerated by patients and results in a potential Th1 weighted immune response