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Prostate specific membrane antigen (PSMA) is an emerging diagnostic and therapeutic target in prostate cancer.

Background The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy estimates have never been generated in these reports. We addressed this void. Material and methods We systematically examined TKI efficacy after IO-failure and generated weighted median progression-free survival (PFS) estimates for Pazopanib, Axitinib, Cabozantinib, Sunitinib. A systematic review according to PRISMA was conducted. PubMed and abstracts were queried. Only studies proving median PFS were included. Weighted medians were computed for each TKI alternative. Results Of 245 articles, nine eligible studies were included in the current study with 952 analysed patients. Weighted PFS medians after any previous IO-based therapy were respectively 13.7 (range from 4.6 to 24.4), 8.1 (range from 4.7 to 13.2), 8.5 (range from 4.7 to 15.2) and 6.9 months (range from 2.9 to 11.6) for Pazopanib, Axitinib, Cabozantinib, Sunitinib. Specific second-line weighted PFS median was 14.8 months (range from 5.6 to 24.4), 10.1 months (range from 6.4 to 13.2), 8.7 months (range from 4.7 to 15.2) and 6.0 months (range from 2.9 to 8.0) for Pazopanib, Axitinib, Cabozantinib, Sunitinib, respectively, after first-line IO. Conclusion Pazopanib results in the longest weighted median PFS, after previous IO-failure, regardless of treatment line, as well as in specific second-line, post-first-line IO failure settings. Pending novel studies, Pazopanib appears to represent the most promising treatment option after prior IO.

Background To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa). Methods Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses. Results We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis. Conclusions After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.

Background Controversy still exists regarding efficacy of multimodality treatment (MMT) vs. radical cystectomy (RC) for urothelial carcinoma of the urinary bladder (UCUB). Methods Within the SEER database (2004-2016), we retrospectively identified patients with stage T2N0M0 UCUB. Competing risks regression (CRR) tested cancer-specific mortality (CSM) and adjusted for other-cause mortality after MMT vs. RC. Exact matching for age was applied. Subgroup analyses focused on differences in chemotherapy or lymph node dissection rates. In sensitivity analyses, we accounted for 40% understaging rate in patients who underwent MMT. Results Of 9862 patients with T2N0M0 UCUB, 2675 (27.1%) underwent MMT vs. 5751 (58.3%) RC vs. 1436 (14.6%) radiotherapy (RT) without chemotherapy. MMT rate increased (annually +3.0%, P Conclusion In patents with T2N0M0, MMT or even more so RT alone may be associated with higher CSM than RC, even in exact age-matched multivariate CRR analyses, which adjust for other-cause mortality. In consequence, patients with T2 UCUB should be informed of this possible CSM disadvantage outside of highly specialized centers.

To evaluate stage at presentation and cancer-specific mortality (CSM) in upper urinary tract tumors according to histologic subtype.Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), we identified patients with upper urinary tract tumors with pure variant histology (UTVH) and pure upper urinary tract urothelial carcinoma (UTUC). Cumulative incidence plots, after propensity score matching for tumor and patient characteristics, addressed CSM. Subgroup analyses addressed efficacy of radical nephroureterectomy (RNU) in stage T1-2 and of chemotherapy in metastatic UTVH patients.Of all 11,809 upper urinary tract tumor patients, 154 (1.3%) harbored squamous cell carcinoma (SCC), 86 (0.7%) adenocarcinoma, 39 (0.3%) neuroendocrine carcinoma, 38 (0.3%) other UTVH, and 11,492 (97.3%) UTUC. UTVH patients were more likely to exhibit metastatic stage disease at diagnosis than UTUC (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P .01). After detailed matching for performance status, only SCC showed significantly higher CSM than UTUC (multivariate HR = 1.71; P .01). Subgroup analyses in stage T1-2 RNU patients showed, relative to UTUC patients, no CSM differences for SCC or adenocarcinoma patients. No significant survival benefit for chemotherapy administration was identified in patients with metastatic SCC or metastatic adenocarcinoma. This study is limited by its sample size and the missing centralized pathologic review.Disease stage at diagnosis is more advanced in UTVH patients than UTUC. Across all stages, CSM is higher for SCC than for UTUC. However, in T1-2 stage disease, RNU results in similar survival in SCC or adenocarcinoma versus UTUC.

Purpose We evaluated efficacy and safety profile of patients with anticoagulation therapy (AT) undergoing holmium laser enucleation of the prostate (HoLEP). Methods Within our prospective institutional database (11/2017 to 11/2019), we analyzed functional outcomes and 30-day complication rates of HoLEP patients according to Clavien–Dindo classification (CLD), stratified according to specific AT vs. no AT. Further analyses consisted of uni- and multivariate logistic regression models (LRM) predicting complications. Results Of 268 patients undergoing HoLEP, 104 (38.8%) received AT: 25.7% were treated with platelet aggregation inhibitors (PAI), 8.2% with new oral anticoagulants (NOAC) and 4.9% with AT-combinations or coumarins bridged with low molecular weight heparins (LMWH/combination). Patients receiving AT were significantly more comorbid (p p p = 0.04), age (OR 1.04, p = 0.02) and bioptical or incidental prostate cancer (OR 2.5, p = 0.01) represented independent risk factors. Conclusion Despite higher overall complication rates in AT patients, major complications were not more frequent in AT patients. HoLEP is safe and effective in anticoagulated patients.

Claudins are promising biomarkers for diagnosis and prognosis or targets for treatment. They play a major role in signal transduction and are important in nearly all aspects of tumorigenesis. Claudin 6 is a member of the claudin family and is part of the tight junction molecule. It is reactivated in several cancer types and serves as prognostic marker in, for example, gastric, breast or non small cell lung cancer. The prognostic role of Claudin 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), is still unclear.The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Claudin 6 was determined by immunohistochemistry.In total, Claudin 6 staining was positive in 55 of 240 type 1 and 30 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed an overall survival of 84% for Claudin 6- compared to 78% for Claudin 6 + in pRCC type 1 tumors (p = 0.449, log-rank) and 68% for Claudin 6- compared to 65.4% for Claudin 6 + in pRCC type 2 tumors (p = 0.364, log-rank).In this study, claudin 6 expression showed no significant association regarding overall survival (OS) and therefore did not qualify as a prognostic marker in pRCC. Future studies will have to determine, whether Claudin 6 plays a prognostic role in other RCC entities. In addition, the function of Claudin 6 as a predictive marker for therapeutic approaches has to be evaluated in future studies.

Simple Summary: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge due to the lack of biomarkers indicating the optimal drug for each patient. This study analyzed blood samples of patients with predominant clear cell mRCC who were treated with the mTOR inhibitor everolimus after failure of one prior tumor therapy. In an exploratory approach, predictive blood biomarkers were searched. We found lower levels of the protein thrombospondin-2 (TSP-2) at the start of the therapy and higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation to be associated with therapy response. Of note, these blood biomarkers had a higher predictive value than baseline patient parameters or risk classifications. Polymorphisms in the mTOR gene appeared to be associated with therapy response, but were not significant. To conclude, it seems feasible to identify patients showing longtime responses to everolimus and possible to increase tumor therapy response rates based on biomarkers for individual therapy selection. Abstract: There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.

Previous cancer-specific mortality (CSM) analyses for different Gleason patterns in Gleason grade group (GGG) 5 cancer were limited by sample size.To test for differences in CSM according to biopsy GG 5 patterns (4 + 5 vs 5 + 4 vs 5 + 5) among patients undergoing radical prostatectomy (RP) or external beam radiation therapy (EBRT).Patients in the Surveillance, Epidemiology and End Results database treated with RP and EBRT (2004-2016) were identified and stratified according to Gleason 4 + 5 versus 5 + 4 versus 5 + 5.RP or EBRT.Kaplan-Meier and multivariable Cox regression models predicting CSM were constructed.Of 17 263 eligible patients with GG 5 cancer at biopsy (RP: n = 7208; EBRT: n = 10 055), 12 705 had Gleason 4 + 5, 3302 had Gleason 5 + 4, and 1256 had Gleason 5 + 5 disease. Median age, prostate-specific antigen (PSA) at diagnosis, and advanced cT and cN stages significantly differed by Gleason pattern (Gleason 4 + 5 vs 5 + 4 vs 5 + 5; all p0.001). The 10-yr CSM rate was 18.2% for Gleason 4 + 5, 28.0% for Gleason 5 + 4, and 39.1% for Gleason 5 + 5 (p0.001). In multivariable analyses for the entire cohort adjusted for PSA, age at diagnosis, and cT and cN stage, Gleason 5 + 4 and Gleason 5 + 5 were associated with 1.6- and 2.2-fold higher CSM, respectively, relative to Gleason 4 + 5. In addition, Gleason 5 + 4 and Gleason 5 + 5 were associated with 1.6- and 2.5-fold, and 1.5- and 2.1-fold higher CSM rates in the RP and EBRT subgroups, respectively, relative to Gleason 4 + 5 (all p0.001).For patients with biopsy GG 5 prostate cancer treated with RP or EBRT, there are important CSM differences by Gleason pattern (4 + 5 vs 5 + 4 vs 5 + 5). Ideally, the individual Gleason pattern should be considered in pretreatment risk stratification.For patients with grade 5 prostate cancer, we found differences in cancer-specific death rates according to the pattern of abnormal cells in the prostate, called the Gleason score. The highest death rate was found for a Gleason pattern score of 5 + 5, followed by Gleason 5 + 4 and then Gleason 4 + 5. These differences were observed for both patients who were treated with prostate removal and patients who underwent radiotherapy.

Context Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes. Objective To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs). Evidence acquisition First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification. Evidence synthesis The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone. Conclusions In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint. Patient summary We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC.

Background: Number of positive prostate biopsy cores represents a key determinant between high versus very high-risk prostate cancer (PCa). We performed a critical appraisal of the association between the number of positive prostate biopsy cores and CSM in high versus very high-risk PCa. Methods: Within Surveillance, Epidemiology, and End Results database (2010–2016), 13,836 high versus 20,359 very high-risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut-offs (≥2–≥12) were tested in Kaplan–Meier, cumulative incidence, and multivariable Cox and competing risks regression models. Results: Among 11 tested positive prostate biopsy core cut-offs, more than or equal to 8 (high-risk vs. very high-risk: n = 18,986 vs. n = 15,209, median prostate-specific antigen [PSA]: 10.6 vs. 16.8 ng/ml

Objective To test 1) contemporary pelvic lymph node dissection (PLND) trends at radical cystectomy (RC) in variant histology bladder cancer (VHBC) patients and urothelial carcinoma of the urinary bladder (UCUB), as well as 2) to test the effect of PLND extent on cancer specific mortality (CSM) after RC. Methods Within the Surveillance, Epidemiology and End Results Registry (SEER, 2004–2016), we identified non-metastatic stage T1-2 or T3-4 VHBC and UCUB patients, who underwent RC. CSM and lymph node invasion (LNI) rates were stratified according to PLND extent, as well as coded continuously in multivariate Cox and logistic regression models. Results Of 19,020 patients, 1736 (9.1%) were coded as having VHBC (46.9% squamous cell carcinoma, 22.5% adenocarcinoma, 18.9% neuroendocrine carcinoma, 11.7% not otherwise specified) vs. 17,284 (90.9%) UCUB. PLND was performed in 80.1 of VHBC vs. 83.5% UCUB patients. In both histological groups, PLND rates increased over time (70.9-89.6% and 76.2-90.1%, both p Conclusion PLND rates do not differ between VHBC and UCUB patients. A potential survival benefit related to more extensive PLND is operational in UCUB patients, but not in VHBC patients.

Objective: To investigate temporal trends in prostate cancer (PCa) radical prostatectomy (RP) candidates. Materials and Methods: Patients who underwent RP for PCa between January 2014 and December 2019 were identified form our institutional database. Trend analysis and logistic regression models assessed RP trends after stratification of PCa patients according to D'Amico classification and Gleason score. Patients with neoadjuvant androgen deprivation or radiotherapy prior to RP were excluded from the analysis. Results: Overall, 528 PCa patients that underwent RP were identified. Temporal trend analysis revealed a significant decrease in low-risk PCa patients from 17 to 9% (EAPC: −14.6%, p < 0.05) and GS6 PCa patients from 30 to 14% (EAPC: −17.6%, p < 0.01). This remained significant even after multivariable adjustment [low-risk PCa: (OR): 0.85, p < 0.05 and GS6 PCa: (OR): 0.79, p < 0.001]. Furthermore, a trend toward a higher proportion of intermediate-risk PCa undergoing RP was recorded. Conclusion: Our results confirm that inverse stage migration represents an ongoing phenomenon in a contemporary RP cohort in a European tertiary care PCa center. Our results demonstrate a significant decrease in the proportion of low-risk and GS6 PCa undergoing RP and a trend toward a higher proportion of intermediate-risk PCa patients undergoing RP. This indicates a more precise patient selection when it comes to selecting suitable candidates for definite surgical treatment with RP.

Objective Relative to urban populations, rural patients may have more limited access to care, which may undermine timely bladder cancer (BCa) diagnosis and even survival. Methods We tested the effect of residency status (rural areas [RA Results Of 222,330 patients, 3496 (1.6%) resided in RA, 25,462 (11.5%) in UC and 193,372 (87%) in UA. Age, tumor stage, radical cystectomy rates or chemotherapy use were comparable between RA, UC and UA (all p > 0.05). At 10 years, RA was associated with highest OCM followed by UC and UA (30.9% vs. 27.7% vs. 25.6%, p p = 0.01). In stage-stratified, fully matched CRR analyses, increased OCM and CSM only applied to stage T1 BCa patients. Conclusion We did not observe meaningful differences in access to treatment or stage distribution, according to residency status. However, RA and to a lesser extent UC residency status, were associated with higher OCM and marginally higher CSM in T1N0M0 patients. This observation should be further validated or refuted in additional epidemiological investigations.

Background Stage-specific guideline recommendations are lacking for chemotherapy in micropapillary carcinoma of the urinary bladder (MCUB). Objective To test the efficacy of stage-specific chemotherapy for MCUB. Design, setting, and participants Within the Surveillance, Epidemiology and End Results (SEER) registry (2001–2016), we identified patients with MCUB and pure urothelial carcinoma of the urinary bladder (UCUB) of all stages. Outcome measurements and statistical analysis Kaplan-Meier survival analyses and multivariate Cox regression models were used to determine cancer-specific mortality (CSM) in addition to power analyses. Results and limitations Of 210 491 patients of all stages, 518 (0.2%) harboured MCUB versus 209 973 (99.8%) UCUB. Stage at presentation was invariably higher in MCUB than in UCUB patients. Of the MCUB patients, 223 (43.1%) received chemotherapy versus 42 921 (20.4%) of the UCUB patients. In MCUB patients, chemotherapy improved CSM-free survival significantly in metastatic stage (hazard ratio [HR] 0.36, p = 0.04). Longer median CSM-free survival was also associated with chemotherapy use in addition to radical cystectomy (RC) versus RC alone in non–organ-confined MCUB (HR 0.69, p = 0.2). Additional power analyses revealed an underpowered comparison. Finally, no CSM difference was recorded in organ-confined MCUB according to the use of chemotherapy in addition to RC versus RC alone (HR 0.98, p = 1). Conclusions Stage at presentation was invariably higher in MCUB than in UCUB patients. Very important CSM reduction was associated with chemotherapy use in metastatic MCUB. A promising protective effect of perioperative chemotherapy might also be applicable to non–organ-confined MCUB, but without sufficient statistical power. Conversely, no association was recorded in organ-confined MCUB. Patient summary Patients with micropapillary carcinoma of the urinary bladder (MCUB) present in higher tumour stages than those with urothelial carcinoma of the urinary bladder. Chemotherapy for MCUB is effective in metastatic stages, but of no beneficial effect in organ-confined stage. In not-yet-metastatic but already non–organ-confined stages, we did not have enough observations to show a statistically significant protective effect of chemotherapy.

Background: The distribution of metastatic sites in upper tract urothelial carcinoma (UTUC) is not well-known. Consequently, the effects of sex and age on the location of metastases is also unknown. This study sought to investigate age- and sex-related differences in the distribution of metastases in patients with UTUC. Materials and Methods: Within the Nationwide Inpatient Sample database (2000–2015), we identified 1,340 patients with metastatic UTUC. Sites of metastasis were assessed according to age (≤63, 64–72, 73–79, and ≥80 years) and sex. Comparison was performed with trend and chi-square tests. Results: Of 1,340 patients with metastatic UTUC, 790 (59.0%) were men (median age, 71 years) and 550 (41.0%) were women (median age, 74 years). The lung was the most common site of metastases in men and women (28.2% and 26.4%, respectively), followed by bone in men (22.3% vs 18.0% of women) and liver in women (24.4% vs 20.5% of men). Increasing age was associated with decreasing rates of brain metastasis in men (from 6.5% to 2.9%; P=.03) and women (from 5.9% to 0.7%; P=.01). Moreover, increasing age in women, but not in men, was associated with decreasing rates of lung (from 33.3% to 24.3%; P=.02), lymph node (from 28.9% to 15.8%; P=.01), and bone metastases (from 22.2% to 10.5%; P=.02). Finally, rates of metastases in multiple organs did not vary with age or sex (65.2% in men vs 66.5% in women). Conclusions: Lung, bone, and liver metastases are the most common metastatic sites in both sexes. However, the distribution of metastases varies according to sex and age. These observations apply to everyday clinical practice and may be used, for example, to advocate for universal bone imaging in patients with UTUC. Moreover, our findings may also be used for design considerations of randomized trials.

To investigate prognostic parameters for the oncological outcome of patients treated for chromophobe renal cell carcinoma (chRCC) in comparison with patients treated for clear cell RCC (ccRCC) using propensity score matching for survival analysis.From 1969 to 2009, we identified 1010 from 3567 patients with RCC. Survival was analyzed using Kaplan-Meier estimate for histological subtypes including 109 chRCC and 901 ccRCC. Uni- and multivariate Cox regression was used to analyze prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Propensity score matching was performed to adjust for differences in patient characteristics among histological subgroups.The median follow-up was 61 months (range 0-289). chRCC showed longer OS (5 year, 90.1%; 10 year, 74.2%; 15 year, 61.4%) and CSS (94.2%, 89.7%, 89.7%) compared with ccRCC (OS 75.7%, 54.9%, 46.1% and CSS 84.7%, 75.4%, 72.2%; P = .002). Multivariate Cox regression revealed histology as a significant prognostic factor. Propensity score matching showed a difference in 72.4% (OS) and 87.2% (CSS) of matching attempts confirming the significant impact of histology. Univariate Cox regression showed nephron sparing surgery, no metastasis and no symptoms at presentation, age65, eosinophilic features, low American Society of Anesthesiologists score, and Charlson Comorbidity Index to be beneficial for CSS. Only age at surgery, metastasis at presentation, and American Society of Anesthesiologists and Charlson Comorbidity Index scores were significant factors for OS in chRCC patients.ChRCC appears to have a favorable outcome compared with ccRCC. Even after adjustment for differences in characteristics known to have an influence on survival by propensity score matching, histology remains a significant prognostic factor.

Obese patients may be predisposed to adverse perioperative outcomes and it is uncertain whether robot-assisted radical cystectomy (RARC) benefits obese patients in comparison to open radical cystectomy (ORC). Thus, we tested the effect of obesity and surgical approach on perioperative outcomes and total hospital charges.Within the National Inpatient Sample database (2008-2015), we identified obese (body mass index ≥30 kg/m2) vs. non-obese patients with non-metastatic bladder cancer treated with RARC or ORC. Estimated annual percent changes and weighted multivariable logistic and linear regression models adjusted for clustering as well as age, comorbidities, hospital volume, and respectively surgical approach, lengths of stay, and/or complications were used.Of all 11,594 patients (unweighted patient count), 1,119 (9.7%) were obese vs. 10,475 (90.3%) were not-obese. Obesity rate increased significantly over time (5.5%-13.3%, annual change: 11%, P = 0.001). RARC, as well as treatment in high volume hospitals was more prevalent in obese vs. non-obese patients (18.3 vs. 14.5% and 40.9 vs. 37.0%, both P0.01). In multivariable regression models, obesity independently predicted overall complications (odds ratio [OR] 1.23, confidence interval [CI]: 1.09-1.42), major complications (OR 1.63, CI: 1.41-1.87), longer hospital stay (OR 1.17, CI: 1.02-1.34) and higher total hospital charges ($+8,260, CI: 3951-12,570), all P0.01). In subgroup analyses in obese patients, RARC was not associated with overall (OR 1.15, P = 0.4) and major complications (OR 1.10, P = 0.6) or length of stay (OR 0.78, P = 0.1) compared with ORC but with higher hospital charges (+$16,794, P = 0.005).Obesity predisposes to higher rates of adverse perioperative outcomes at radical cystectomy. The benefit of RARC could not be validated in obese patients.

Urinary incontinence in men after radical prostatectomy affects strongly quality of life. If conservative treatment fails, surgical treatment consists of implantable devices. If the requirement of manual dexterity in the artificial sphincter is to be avoided, the ProACT system offers a readjustable system, which shows good continence, but also high revision rates. Aim of our single-centre, single-surgeon study was to evaluate the success and revision rates of ProACT over long-term follow-up and if repeat ProACT implantation after failure would be a reasonable strategy.In May 2017, follow-up of all patients who underwent ProACT implantation between 2003 and 2013 was obtained. Parameters were numbers of pads used, filling volume of balloons, and patient-reported satisfaction. Furthermore, revisions were noted.Between 2003 and 2013, 134 patients were implanted a ProACT system. Median age was 71 years; median follow-up was 118 months. 112 implantations were successful (82.6%) and the number of pads used decreased significantly (p 0.005). 63 patients were revised and 49 were successful (77.8%). No differences in success rate, pads used, or filling volume were seen (all p 0.8). In a second revision, again, no differences in success rate or pads used were noted (all p 0.7). Patients' personal satisfaction was high despite the high revision rate.In the hands of an experienced surgeon, ProACT is a safe and effective therapy for post-prostatectomy incontinence especially if mayor surgery is to be avoided. Revision rates are high, but the results of ProACT reimplantation are comparable to the results after the first implantation.

Hintergrund: Die robotisch assistierte partielle Nephrektomie (RAPN) zeigt im Gegensatz zur konventionellen laparoskopischen Nierenteilresektion eine steile Lernkurve und kurzere warme Ischamiezeiten (WIZ). Dies ermoglicht es Patienten mit einem Nierentumor im Stadium cT1a, bei vergleichbaren onkologischen Ergebnissen, die Vorteile eines minimalinvasiven Operationsverfahrens zukommen zu lassen. Ziel der vorliegenden Studie war es, das perioperative Outcome unserer Patienten nach RAPN zu untersuchen und die Lernkurve anhand charakteristischer Werte, wie z. B. der WIZ, zu illustrieren. Material und Methode: Die Daten von 109 Patienten, die in unserer Klinik von Januar 2010 bis April 2015 einer RAPN zugefuhrt wurden, wurden retrospektiv, hinsichtlich operativen, laborchemischen und onkologischen Outcomes, analysiert. Die Komplikationen bis 30 Tage postoperativ wurden erfasst. Das groste Patientenkollektiv, welches von einem Operateur versorgt wurde, wurde hinsichtlich signifikanter Unterschiede der WIZ, Operationszeit, Verlust der pra- und postoperativen glomerularen Filtrationsrate (GFR), sowie des Blutverlustes zwischen den ersten und den zweiten 30 Fallen im Kollektiv untersucht. Ergebnisse: Die durchschnittliche WIZ lag bei 18,4 min (SD±10,2), die durchschnittliche Operationszeit betrug 199 min (SD±20). Der durchschnittliche Blutverlust wurde mit 657 ml (SD±715 ml) angegeben. Der durchschnittliche Verlust der GFR betrug 4,99 mg/dl/1,73 m2 (SD±15,44). Es wurden 83 (76%) maligne Lasionen entfernt. 11(10%) Patienten hatten einen R1 Status, 1 Patient hatte einen R2 und 2 einen Rx Status. Die Gesamtkomplikationsrate lag bei 22%. Intraoperative Komplikationen traten bei 2 der Patienten auf. Nach Clavien-Dindo klassifiziert traten Grad 1 und 2 Komplikationen bei 6% und Grad 3 und Grad 4 Komplikationen bei 13% der Patienten postoperativ auf. Die WIZ war signifikant mit der Erfahrung des Operateurs nach 30 operierten Fallen verknupft. Fur die Operationszeit, den Verlust an GFR oder Blut ergab sich kein signifikanter Zusammenhang. Schlussfolgerung: Die erhobenen Daten decken sich mit den in der Literatur beschriebenen Ergebnissen. Die RAPN ist ein sicheres Operationsverfahren mit einer steilen Lernkurve. Unserer Erfahrung nach sind 30 Falle ausreichend, um ein gutes perioperatives Ergebnis zu erzielen. Einschrankungen bestehen im retrospektiven Design der Untersuchung mit zum Teil unvollstandiger Dokumentation einiger Daten.

Zertifizierte Prostatazentren proklamieren die Deckungsgleichheit von Prozess- und Ergebnisqualitat ihrer Prostatakarzinombehandlung. Leitliniengetreue Therapie nach Vorstellung des Patienten in der interdisziplinaren Konferenz und regelmasig dokumentierte Nachsorge sind indes keine Garantie fur eine gute Ergebnisqualitat (Komplikationsfreiheit, Kontinenz, erektile Funktion, negative Absetzungsrander, biochemische Rezidivfreiheit), welche von nicht im Rahmen der Zertifizierung erfassten Faktoren masgeblich beeinflusst wird. Ein Zusammenhang zwischen dem Uberschreiten der Mindestoperationszahlen und einer Qualitatssicherung besteht, wenn uberhaupt, nur vage und rechtfertigt auf keinen Fall die fur die Zertifizierung notwendigen absoluten Zahlen. Obschon gute Messinstrumente fur eine Pentafecta-Analyse zur Verfugung stunden, erschopft sich die Erfassung der Ergebnisqualitat des Zentrums funktionell in Fragebogen und onkologisch in der undifferenzierten Einforderung einer pT2R1-Rate von

In bladder cancer (BCa) patients undergoing radical cystoprostatectomy (RCPx), concomitant prostate cancer (PCa) is a common finding. Up to now there is no clear evidence to suggest that concomitant PCa is a predictor of outcome in these patients. Aim of this study was to assess incidence and clinicopathologic characteristics of concomitant PCa in RCPx specimen and correlate it to survival parameters from a single-centre material over two decades. All men who had undergone RCPx for BCa at our institution between 1994 and 2013 were included in this study. Clinicopathologic parameters for BCa and PCa were evaluated and correlated with outcome parameters. Survival analysis was performed for the subgroup of nonmetastatic organ-confined BCa to evaluate the role of concomitant Gleason Score (GS) ≥7 PCa. Of 945 men who had undergone RCPx for BCa, concomitant PCa was present in 237 patients (25.1 %). There was a significant increase in PCa incidence from 18.9 to 32.3 % between 1994 and 2013 (p = 0.009). Concomitant PCa represented a more aggressive phenotype at the end of the study (p = 0.037). In nonmetastatic organ-confined BCa, concomitant GS ≥7 PCa (HR 3.09; p = 0.0001) and age > 68 (HR 1.80; p = 0.0004) were independent negative predictors for overall survival. Concomitant PCa in RCPx specimen of BCa patients is a common finding. The incidence of concomitant PCa has significantly increased within 2 decades, presenting a more aggressive phenotype. Age and in particular concomitant GS ≥7 PCa are independent prognosticators for poor survival in patients with nonmetastatic organ-confined BCa.

Bone metastasis develops in 30% of all patients with renal cell carcinoma. We elucidated the mechanisms that lead to and predict bone metastasis of renal cell carcinoma.Nine renal cell carcinoma primary cell lines and 30 renal cell carcinoma tissue specimens (normal and tumor tissue) were collected from 3 patients with no metastasis and 10 with lung or bone metastasis within 5 years after nephrectomy. Cell migration was analyzed in a Boyden chamber and proliferation was assessed by bromodeoxyuridine incorporation. Adhesion to fibronectin, and collagen I and IV was determined after cell staining. The expression and/or activity of cellular signaling molecules was quantified by Western blot.Compared to renal cell carcinoma cells from patients without metastasis, the migration of cells from patients with bone metastasis was enhanced 13.5-fold (p = 0.034), and adhesion to fibronectin and collagen I was enhanced 5.8-fold and 6.1-fold (p = 0.002 and 0.014, respectively). In general proliferation was decreased in metastasizing cells. In accordance with these results we detected higher activity of AKT (p = 0.011) and FAK (p = 0.054), higher integrin α5 expression (p = 0.052) and lower PTEN expression in primary cells from patients with bone metastasis compared to nonmetastasizing cells. An almost similarly altered expression pattern was also observed in the renal cell carcinoma tissue specimens and the normal renal tissue of patients with bone metastasis.We describe evidence that molecular predispositions determine the potential for bone metastasis to develop in renal cell carcinoma, which may serve as prognostic markers after initial tumor detection.

Hintergrund Vesikovaginalfisteln treten in Industrienationen deutlich seltener auf als in Schwellenlandern des aquatorialen Fistelgurtels. Durch fehlende medizinische Schwangerschaftsbetreuung bei jungen Primaparae vor Abschluss des Wachstums hervorgerufene Geburtsfisteln gehoren in Deutschland der Vergangenheit an, dafur treten v. a. iatrogene Blasen-Scheiden-Fisteln an deren Stelle. Steigende Operations- und Bestrahlungsfrequenzen, aber auch vergessene vaginale Fremdkorper oder ungehemmtes Tumorwachstum rufen sie v. a. bei alteren Patientinnen hervor. Komorbiditat und senile Genitalatrophie erschweren die operative Therapie bei gleichzeitig schlechten Erfolgsaussichten einer konservativen passageren transurethralen Dauerableitung.

In den letzten Jahren wurden kleine Raumforderungen der Niere vermehrt als Zufallsbefund radiologischer oder sonographischer Untersuchungen mit anderer Zielsetzung detektiert. Die organerhaltende Nierentumorresektion hat sich in Form der offenen partiellen Nephrektomie (OPN) international als Referenzstandard der Therapie von Nierentumoren

Einer der Hauptmetastasierungsorte des Nierenzellkarzinoms (NZK) sind die Knochen, ein Gewebe mit einer hohen Konzentration an Calciumionen. Extrazellulares Calcium wird von Zellen uber den calciumsensitiven Rezeptor (CaSR) detektiert. Um einen Hinweis darauf zu bekommen, inwieweit Calcium fur die Knochenmetastasierung eine Rolle spielt, wurde der CaSR in Tumorproben und primaren NZK-Zellen von Patienten quantifiziert, die innerhalb von 5 Jahren nach Nephrektomie metastasenfrei bleiben oder die Knochen- oder Lungenmetastasen entwickelt haben. Dabei zeigte sich eine erhohte Expression des CaSR in Gewebeproben und den Zellen von Patienten, die Knochenmetastasen entwickelt haben. In funktionellen Analysen konnte in knochenmetastasierenden Zellen eine hohere Sensitivitat gegenuber Calcium bzgl. der Proliferation und chemotaktischen Migration nachgewiesen werden. Diese Effekte beruhen auf den dem CaSR nachgeschalteten Signalwegen uber AKT, PLCg, JNK und p38, wie in Phosphokinasearrays und Western-Blot-Analysen gezeigt werden konnte. Inwieweit sich der CaSR als ein neuer Marker fur die knochenspezifische Metastasierung des NZK eignet, ware noch zu prufen.

OBJECTIVES To determine the long-term oncological outcome of organ-confined (

Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of RCC, after clear cell (ccRCC) and papillary RCC. Its lower incidence and frequent exclusion from clinical trials might be why chRCC characteristics have not been extensively studied. The aim of our study was to examine tumor characteristics and long-term prognosis of chRCC compared to ccRCC. We collected 4,210 evaluable patients subjected to surgery for chRCC (n = 176) or ccRCC (n = 4,034) at five centers in Germany (University Hospitals of Hannover, Homburg/Saar, Mainz, Ulm, and Marburg) between 1990 and 2010. Patients with chRCC were significantly younger (mean, 60.1 vs. 62.1 years) and tended to be more frequently female (43.8 vs. 36.5 %). Although Fuhrman grade and median tumor diameter were not significantly different, significantly fewer patients with chRCC than with ccRCC presented with high tumor stage or metastasis at diagnosis (18.5 vs. 43.8 %). Moreover, significantly more chRCC patients were treated with partial nephrectomy (41.5 vs. 26.2 %). Accordingly, 5-year cancer-specific survival (CSS) rates were 83.2 % for chRCC against 75.8 % for ccRCC patients (p = 0.014, log rank). However, in multivariate analysis, chromophobe subtype was not confirmed as a significant positive prognostic factor for RCC (HR 0.88, 95 % CI 0.63-1.24; p = 0.48 Cox regression). This is one of the largest studies to date showing that chRCC is associated with a significantly lower risk of locally invasive tumor growth and metastatic disease than ccRCC. We conclude that the clinical behavior of chRCC is less aggressive than that of ccRCC, independent of Fuhrman grade or tumor size.

Seit 20 Jahren haben spannungsfreie alloplastische Schlingenplastiken (SFAS) die Chirurgie der weiblichen Belastungsinkontinenz revolutioniert. Das Verfahren hat sich in grosen Vergleichsstudien bei einfacher Erlernbarkeit, minimaler Invasivitat mit entsprechend kurzen Operationszeiten und prinzipiell ambulanter Durchfuhrbarkeit in Bezug auf Langzeiteffektivitat der Kolposuspension als ebenburtig erwiesen und flachendeckend durchgesetzt. Die Zahl der Inkontinenzoperationen hat sich verdreifacht, was auch einen zwangslaufigen Einfluss auch die Komplikationszahlen haben muss. Demgegenuber ist die Sakrokolpopexie nach wie vor die Standardoperation des weiblichen Deszensus in urologischer Hand geblieben, da samtliche neuen Verfahren nicht an die Effektivitat und Komplikationsarmut dieser Operation heranreichen. Gleichwohl mussen Komplikationsmoglichkeiten benannt und ihre Ursachen erkannt werden, um auch zukunftig hochsten Qualitatsanspruchen genugen zu konnen. Mogliche SFAS-Komplikationen werden sowohl in ihrer Haufigkeit als auch in ihrer Beherrschbarkeit unterschatzt. Komplikationsmoglichkeiten der Inkontinenz- und Deszensuschirurgie werden vorgestellt und moglichen Ursachen zugeordnet. Aus der Kenntnis der Pathophysiologie und der Komplikationsursache kann dann unter Hinzuziehung einer postoperativen Komplikationsdiagnostik ein patientenindividualisiertes Komplikationsmanagement erfolgen. Zur Vermeidung von Komplikationen sollte der Patient praoperativ konservativ ausbehandelt und vollstandig (auch urodynamisch) untersucht werden. Eine postoperative Urodynamikkontrolle hilft bei der Dokumentation des Operationserfolges genauso wie bei der Identifizierung und Graduierung von Komplikationen.

Die urologischen Tumoren machen ca. 40 % aller soliden Tumorentitaten aus. 30 % der Patienten entwickeln synchrone oder metachrone Organmetastasen. Die Metastasenresektion verbessert in Abhangigkeit der Tumorentitat und -charakteristika das Uberleben der Patienten. Die Metastasenchirurgie ist ein fester Bestandteil des multimodalen Therapiekonzepts der Patienten mit nicht-seminomatosen Keimzelltumoren im fortgeschrittenen Stadium. Nur die chirurgische Inoperabilitat spricht gegen eine Metastasenresektion. Die Resektion hamatogener Metastasen beim Nierenzellkarzinom gehort seit Jahrzehnten zur Standardtherapie. Die Patientenselektion ist der entscheidende Faktor fur einen Uberlebensvorteil. Wichtige Prognostikatoren stellen Allgemeinzustand, Metastasenanzahl, -lokalisation, und -grose dar, die zur Konsultation und Selektion der Patienten beitragen. Nur bei einem Ansprechen auf eine systemische Therapie sollten Metastasen im individuellen Fall beim Urothelkarzinom oder Peniskarzinom entfernt werden. Die aktuellen Leitlinien und die Literatur sprechen gegen eine Resektion von hamatogenen Metastasen des Prostatakarzinoms. In diesem Artikel werden Grunde gegen eine Metastasenresektion in Anlehnung an aktuelle Leitlinien und Literaturangaben dargestellt.

Introduction Open simple prostatectomy is a well-established and effective operation for prostate volumes greater than 80 gm but also associated with bleeding and urinary incontinence. To benefit from the advances of laparoscopy, robot-assisted simple prostatectomy was established. We determined the learning curve of this minimally invasive surgery by evaluating the first procedures by an experienced robotic surgeon. Methods Patients presenting for surgical therapy with prostate volumes greater than 80 gm were considered for the study. Evaluation included validated questionnaires preoperatively, and at 6 and 12 weeks postoperatively. Blood loss, transfusions, operation time and pad use after catheter removal were documented. The experience based on the results from 18 cases treated with robot-assisted simple prostatectomy by one of us (JWT) is presented. Results Mean age of the 18 patients was 71.2 years, mean enucleated prostate volume was 91 gm and mean preoperative flow was 9.0 ml/second. I-PSS and QoL values improved significantly from 25 to 6.1 (p Conclusions Robot-assisted simple prostatectomy is a safe and effective operation for benign prostatic hyperplasia, which can be learned with good results in a rather short time.

Modern diagnostic ultrasound and cross-sectional imaging has enabled the detection of increasing numbers of renal tumours. The aim of this study was to investigate the tumour- and patient-specific characteristics and prognosis of small renal cell carcinomas (RCCs) after surgical resection.The study included 2197 patients who underwent surgical resection of histologically confirmed RCC ⩽ 4 cm between 1990 and 2011. Median (mean) follow-up was 56.2 (65.5) months.At the time of surgery, tumours were staged as pT ⩾ 3a in 175 (8.0%) cases, 134 (6.2%) were poorly differentiated and 75 (3.5%) were metastasised. The larger the tumour size, the higher was the risk of presenting with stage pT ⩾ 3a (p0.001), poor tumour differentiation (p = 0.004), microscopic vascular involvement (p = 0.001) and collecting system invasion (p = 0.03). The 5-year cancer-specific survival (CSS) rate was 93.8% for stage pT1a versus 79.4% for stage pT ⩾ 3a (p0.001), and it was 93.7% for G1-2 versus 76.8% for G3-4 differentiation (p0.001). Multivariate analysis identified age in years (hazard ratio (HR) 1.04, p0.001), metastatic disease (HR 12.5, p0.001), tumour differentiation (HR 2.8, p0.001) and non-clear cell histology (HR 0.51, p = 0.02) as independent prognosticators for CSS in patients with small RCC. Interestingly, the 5-year cancer-specific mortality rate for pT1a N/M0 patients was 5.8%.This large multicenter study has clearly shown that, though most small RCC have a low pathological stage and a good prognosis, there is also a small but significant subgroup of these tumours that are already locally advanced or poorly differentiated.

Objectives To evaluate the clinical efficiency of a third generation electromagnetic shock wave lithotripter, the Lithoskop® (Siemens, Erlangen, Germany), regarding outcomes, stone disintegration, retreatment and complication rates. To compare the results of the Lithoskop with other currently available systems and the reference standard lithotripter, the HM-3 (Dornier MedTech Europe GmbH, Wessling, Germany). Patients and Methods We analysed the data from 183 patients, including 13 children, undergoing extracorporeal shock wave lithotripsy (ESWL) for renal and ureteric calculi collected from a prospectively populated database. Outcomes were assessed by plain abdominal film of kidney, ureter and bladder and renal ultrasonography for radiopaque and computerized tomography for radiolucent stones 1 day after treatment and after 3 months. We analysed stone size and location before and after treatment, stone disintegration rate, retreatment rate, stone-free and residual fragment rates after 3 months, along with auxiliary procedures and complications. Results The mean (range) patient age was 48.6 (1.3–81.4) years, including 13 children with a mean (range) age of 8.4 (1.3–16.7) years, and 77% of the patients were male. In all, 46% of the calculi were localized in the kidney and 54% in the ureter. Renal stones were localized in the upper, middle and lower calyx and in the renal pelvis in 9, 29, 30 and 32% of patients, respectively. Ureteric stones were localized in the upper, mid- and distal ureter in 29, 19 and 52% of patients, respectively. The median (range) stone size before ESWL was 10 (4–25) mm in the kidney and 8 (4–28) mm in the ureteric calculi. The overall stone-free rate after 3 months was 91% (88% for renal and 93% for ureteric calculi); the mean number of sessions to achieve these rates was 1.3. Stone-free rates and the required number of sessions were determined only by stone size. In 7.1% of the patients (n = 13) post-interventional auxiliary procedures were necessary. We observed one perirenal haematoma as a major complication (0.5%), but this did not require any further therapy. Conclusions Clinical stone-free rates with the Lithoskop are high and similar to those of other available systems, including the reference standard HM-3 lithotripter. Retreatment and complication rates are low, supporting the use of ESWL as first-line therapy for urinary calculi

Introduction: The study aimed to compare the incidence of cardiovascular events (CVEs) after donor nephrectomy (DN) and radical tumor nephrectomy (RN), according to an estimated glomerular filtration rate (eGFR), were evaluated over time. Materials and Methods: Follow-up was collected for DN who underwent surgery from 1998 to 2007 for CVE and renal function. All DN were matched for age to patients treated by RN or adenoma enucleation (control group), who were eligible for DN. eGFR was estimated using the Cockgroft-Gould formula. Patients with preoperative comorbidities were excluded. Results: Thirty DN (median age 48.9 years) were included with a median follow-up of 138.5 months (interquartile range 119-159). No significant differences in patients' characteristics were found preoperatively (p > 0.5). Four out of 30 DN developed a CVE (3 myocardial infarctions (MI), 1 stroke), 2 of 30 patients in the control group (both MI) and 8 of 30 RN patients (6 MI, 2 strokes, p > 0.05). Arterial hypertension developed in 14 DN (46.7%), in 12 (40%) after RN and in 15 controls. The CVE occurred after a median time of 68 months (5-231) and were related to a drop of ∼30% in the eGFR irrespective of the group. Conclusion: Decline of renal function after nephrectomy is the main risk factor for CVE. Close monitoring of renal function and new onset hypertension is warranted.