Time Trends in Causes of Death in People With HIV: Insights From the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in AIDS-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years are scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005 and 2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female sex at birth. These deaths included 147 (9.0%) HIV/AIDS-related deaths, 373 (22.9%) due to non-AIDS, non-hepatic cancers, 166 (10.2%) liver-related deaths, and 158 (9.7%) cardiovascular-related deaths. The median age at death (interquartile range) increased from 45.0 (40.0-53.0) years in 2005-2007 to 61.0 (56.0-69.5) years in 2020-2022. HIV/AIDS- and liver-related deaths decreased, whereas deaths from non-AIDS, non-hepatic cancers increased and cardiovascular-related deaths remained relatively stable. CONCLUSIONS: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus coinfection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbid conditions, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

Chemsex drugs on the rise: a longitudinal analysis of the Swiss HIV Cohort Study from 2007 to 2017.

OBJECTIVES: Chemsex refers to the use of sex-enhancing drugs among men who have sex with men (MSM) in combination with specific sexual and social behaviours. Longitudinal data on this development and the associated health risks are scarce. METHODS: Data on all recreational drugs reported in the Swiss HIV Cohort Study (SHCS) from 2007 to 2017 were collected. Drug use was analysed longitudinally for all drug classes. In addition, potential associations between patient characteristics and the consumption of methamphetamine, γ-hydroxybutric acid/γ-butyrolactone (GHB/GBL), 3,4-methylenedioxymethamphetamine (MDMA/XTC), cocaine and amphetamine were analysed. RESULTS: We analysed 166 167 follow-up entries for 12 527 SHCS participants, including 7101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, we observed a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P < 0.001) and GHB/GBL (from 1.0 to 3.4%; P < 0.001). The use of each of the potentially sex-enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with nonsteady partners, and higher prevalences of depression, syphilis and hepatitis C. CONCLUSIONS: The significant increase in the use of chemsex drugs among MSM in the SHCS and the strong association with coinfections and depression highlights the need for harm reduction programmes tailored to MSM. According to our results, improving knowledge about recreational drugs is important for all health care professionals working with people living with HIV.

Rapid decline of anti-hepatitis C virus (HCV) antibodies following early treatment of incident HCV infections in HIV-infected men who have sex with men.

OBJECTIVES: Following clearance of incident hepatitis C virus (HCV) infections, HCV antibody levels may decline, resulting in seroreversion. It is unclear to what extent HCV antibody level trajectories differ between patients with treatment-induced sustained virological response (SVR), those with spontaneous clearance and those with untreated replicating HCV infection. We investigated HCV antibody level dynamics in HIV-infected MSM with different clinical outcomes. METHODS: We investigated anti-HCV antibody level dynamics following an incident HCV infection in 67 HIV-infected men who have sex with men (MSM) with different clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated replicating infection (n = 22). Antibody levels were measured at the time of HCV diagnosis, and at yearly intervals for 3 years thereafter. RESULTS: At baseline, median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5 sample to cut-off (S/CO) for SVR, spontaneous clearance and untreated infection, respectively. Over 3 years of follow-up, SVR was associated with a more pronounced decrease in anti-HCV levels compared with spontaneous clearance and untreated infection [median decline 71% [interquartile range (IQR: 43-87%), 38% (IQR: 29-60%) and 12% (IQR: 9-22%), respectively; P < 0.001]. Seroreversions occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with spontaneous clearance. A shorter delay between time of infection and treatment start correlated with higher rates of decline in antibody levels. Seven patients experienced a reinfection. CONCLUSIONS: Treatment-induced HCV clearance was associated with a more pronounced decline in anti-HCV antibody levels and with higher rates of seroreversion compared with spontaneous clearance or untreated replicating HCV infection among HIV-infected MSM with incident HCV infections. Rapid clearance of HCV RNA following early HCV treatment might impair the development of persistent antibody titres.

On the potential of a short-term intensive intervention to interrupt HCV transmission in HIV-positive men who have sex with men: A mathematical modelling study.

Increasing access to direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection and decelerating the rise in high-risk behaviour over the next decade could curb the HCV epidemic among HIV-positive men who have sex with men (MSM). We investigated if similar outcomes would be achieved by short-term intensive interventions like the Swiss-HCVree-trial. We used a HCV transmission model emulating two 12-months intensive interventions combining risk counselling with (i) universal DAA treatment (pangenotypic intervention) and (ii) DAA treatment for HCV genotypes 1 and 4 (replicating the Swiss-HCVree-trial). To capture potential changes outside intensive interventions, we varied time from HCV infection to treatment in clinical routine and overall high-risk behaviour among HIV-positive MSM. Simulated prevalence dropped from 5.5% in 2016 to ≤2.0% over the intervention period (June/2016-May/2017) with the pangenotypic intervention, and to ≤3.6% with the Swiss-HCVree-trial. Assuming time to treatment in clinical routine reflected reimbursement restrictions (METAVIR ≥F2, 16.9 years) and stable high-risk behaviour in the overall MSM population, prevalence in 2025 reached 13.1% without intensive intervention, 11.1% with the pangenotypic intervention and 11.8% with the Swiss-HCVree-trial. If time to treatment in clinical routine was 2 years, prevalence in 2025 declined to 4.8% without intensive intervention, to 2.8% with the pangenotypic intervention, and to 3.5% with the Swiss-HCVree-trial. In this scenario, the pangenotypic intervention and the Swiss-HCVree-trial reduced cumulative (2016-2025) treatment episodes by 36% and 24%, respectively. Therefore, intensive interventions could reduce future HCV treatment costs and boost the benefits of long-term efforts to prevent high-risk behaviour and to reduce treatment delay. But if after intensive interventions treatment is deferred until F2, short-term benefits of intensive interventions would dissipate in the long term.

Robot-sewn ileoileal anastomosis during robot-assisted cystectomy.

PURPOSE: To analyze the feasibility and perioperative results of patients undergoing robot-assisted cystectomy with intracorporeal urinary diversion and robot-sewn ileoileal anastomosis. METHODS: This is a mono-centric analysis of perioperative data from 48 consecutive patients undergoing robot-assisted cystectomy with intracorporeal urinary diversion and robot-sewn ileoileal anastomosis. Data include the preoperative variables, operative and postoperative course and complication rates related to bowel anastomosis. End points were time spent for anastomosis and intra- and postoperative complication rates. RESULTS: Median operating time was 23.0 (13-60) min for the ileoileal anastomosis. Median overall operating time was 295 (200-780) min, with a median of 282 (200-418) min and 414.0 (225-780) min for the ileum conduit (N = 35) and ileal neobladder (N = 13). Two patients developed paralytic ileus; in another patient acute peritonitis occurred, but was caused by urinary leakage and therefore unrelated to the bowel anastomosis. No anastomotic leakage was noticed. Costs for the robot-sewn anastomosis was 8€ compared to 1250€ for a stapled anastomosis which was performed in previous cases. Limitations are the non-comparative nature of the analysis and the limited number of patients. CONCLUSIONS: Robot-sewn ileoileal anastomosis is feasible with low complication rates. Compared to the stapled anastomosis, a robot-sewn ileoileal anastomosis may serve as an alternative and cost-saving approach.

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials.

BACKGROUND: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. PATIENTS AND METHODS: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. RESULTS: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. CONCLUSION: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. CLINICAL TRIALS NUMBER: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).

[The importance of pathology in the German prostate cancer study PREFERE]. / Die Bedeutung der Pathologie in der deutschen Prostatakrebsstudie PREFERE.

Prostate cancer is the most common carcinoma of elderly males and holds the third place in the ranking of cancer-specific mortality. However, total mortality rate of 3 % is low and half of the patients die from other diseases, which is for the most part due to significantly improved diagnostic methods and the increasing use of prostate-specific antigen (PSA) screening. This has led to a stage migration towards early tumor stages that are prognostically heterogeneous and require differentiated treatment. The German and European guidelines recommend four therapy options (i.e. radical prostatectomy, percutaneous irradiation, permanent seed implantation and active surveillance) for localized prostate cancer and from contemporary study data it is unclear which therapy is most beneficial. This will be the subject of the PREFERE trial, a prospective randomized multicentre trial which plans to recruit 7,600 patients and to observe them over a period of up to 17 years. The histopathological diagnosis of the primary biopsy plays a crucial role in the inclusion criteria, as this article outlines in detail.

[Morbidity and mortality in HIV infection]. / Morbidität und Mortalität der HIV-Infektion.

Combination antiretroviral therapy (cART) has dramatically improved the prognosis of HIV-infected individuals, with a close to a normal life expectancy in a significant proportion of treated individuals. Upon start of cART, HIV-induced immune deficiency can be prevented or, if already present, reconstituted. Remaining morbidity and mortality is partly due to the late diagnosis of HIV infection or late presentation of patients, when CD4-T-cells have already fallen below 200 cells/µl and/or AIDS-defining conditions have manifested. Further reasons for remaining morbidity and mortality are related to co-morbidities such as viral hepatitis and tumors, particularly in older patients. As HIV-infected patients become older, increasing co-morbidities and socio-economic costs may become a challenge in the future.

[Robot-assisted kidney transplantation]. / Roboterassistierte Nierentransplantation.

BACKGROUND: Robot-assisted surgery has become widely adopted in urology due to advantages in comparison with laparoscopic or open approaches. Robot-assisted living kidney transplantation is one of the most challenging procedures in urology regarding technical, but also psychological and ethical aspects, and is currently routinely performed in two German departments. OBJECTIVES: The goal was to analyze and compare current evidence and experiences of robot-assisted living kidney transplantation in Europe and in Germany. MATERIALS AND METHODS: A systematic search was performed to identify relevant publications. They were compared with latest results from two German academic centers (Halle and Homburg/Saar). RESULTS: In 2015, robot-assisted living kidney transplantation was performed for the first time in Europe. Since then, 8 academic centers have established this procedure. Until today, more than 180 robot-assisted kidney transplantations have been performed. Short- and mid-term results have proven to be excellent with low complication rates. Apart from 3 transplant losses because of arterial thrombosis and 5 surgical re-explorations due to hematoma, no other noteworthy complications occurred. There was only 1 lymphocele. The median blood loss was 150 ml and kidney function after 1 year was unchanged in comparison with postoperative day 30. CONCLUSIONS: Robot-assisted living kidney transplantation is not inferior to the open approach. Even superiority is not unlikely because problematic situations such as obese patients or complex vascular anatomy can be handled safely. In particular, the development of lymphocele and wound healing disorders appear to be significantly decreased compared to conventional surgery.

Quality of life and self-esteem for children with urinary urge incontinence and voiding postponement.

PURPOSE: Urge incontinence and voiding postponement are common subtypes of daytime wetting in children. We analyzed health related quality of life for children with urge incontinence and voiding postponement, and healthy controls at 2 centers. MATERIALS AND METHODS: We examined a total of 49 consecutive children 5 to 13 years old who presented with urge incontinence (22) or voiding postponement (27), and 32 controls matched for age and sex. Health related and overall quality of life were measured with generic questionnaires, and self-esteem was measured with the Piers-Harris questionnaire. RESULTS: Health related quality of life was significantly reduced in parent rating but not in child rating in the incontinent vs control group (total mean parent score 73 vs 78, child 76 vs 76). Children with voiding postponement have the lowest health related quality of life. Overall quality of life was significantly reduced in children with incontinence, while self-esteem did not differ. Children with externalizing disorders generally have the lowest health related and overall quality of life. CONCLUSIONS: Health related and overall quality of life are useful constructs, and are reduced in children with daytime incontinence by parental rating. In comparison, children rate their quality of life as being higher. Quality of life is lowest with externalizing behavioral disorders, as in children with voiding postponement. Due to comorbid behavioral disturbances, children with voiding postponement often need additional assessment, counseling and treatment.

[Trivialization of prostate cancer? : Stage shift and possible causes]. / Bagatellisierung des Prostatakarzinoms? : Stadien-Shift und mögliche Ursachen.

BACKGROUND: According to the strongly negative grade D recommendation of the U.S. Preventive Services Task Force in 2012, the prostate-specific antigen (PSA) test was not only not recommended but was also warned against. As a result in the USA there was a stage shift towards more advanced tumor stages under the newly detected prostate cancers; however, in contrast to the highly questionable American PLCO study, the European ERSPC study showed a clear reduction in prostate cancer-related mortality. OBJECTIVE: In this patient cohort it was investigated whether the tumor stage distribution in curatively treated prostate cancer has significantly changed, whether this has an influence on the perioperative results and complication rates and how these changes could have occurred. MATERIAL AND METHODS: Patients after radical prostatectomy from 2008 to 2010 were compared to those from 2017. Demographic data, intraoperative courses, perioperative and postoperative complications and histopathological results were compared. RESULTS: A total of 1276 operations were analyzed. Preoperative PSA levels showed a significant increase in 2017 (10.5 ± 13.4 ng/ml vs. 8.4 ± 9.1 ng/ml, p = 0.032). The pathological staging revealed a 20% increase in T3 tumors (49.4% versus 29.0%, p < 0.001). Correspondingly, moderately and poorly differentiated cancers and therefore those with higher aggressiveness were significantly more frequent with 11.2% (p < 0.001) and 10.4% (p < 0.001), respectively. The number of patients with lymph node metastases at prostatectomy even increased fourfold (4.5% vs. 16.9%, p < 0.001). CONCLUSION: In the radical prostatectomy group, there was a shift to unfavorable and metastatic tumor stages. This negative trend seems largely to be caused by a lower acceptance of early detection by means of PSA determination.

In vivo evaluation of the uptake of [(123)I]FIAU, [(123)I]IVFRU and [(123)I]IVFAU by normal mouse brain: potential for noninvasive assessment of HSV-1 thymidine kinase gene expression in gliomas.

Radioiodinated 5-iodo-1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)uracil (F *IAU) is most commonly used for noninvasive assessment of herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression. However, it does not permeate the intact blood-brain barrier (BBB) because of its moderate lipophilicity. In this work, three iodo-nucleosides, FIAU, IVFRU, and IVFAU, were radiolabeled with iodine-123 and tested for permeation of the BBB in mice and for potential measurement of HSV-1-tk gene expression in gliomas. The results demonstrate that brain uptake and retention of these nucleosides is not directly related to their lipophilicity. The low brain uptake of IVFAU, in conjunction with its higher and constant brain/blood ratio, may reflect greater stability against hydrolysis of the N-glycosidic bond. In vivo PET evaluations of [(124)I]IVFRU and [(124)I]IVFAU in tumor-bearing mice are warranted.

[Robot-assisted (da Vinci) laparoscopy: the beginning of a new era in operative urology?]. / Robotisch unterstützte (DaVinci-)Laparoskopie : Beginn eines neuen Zeitalters in der operativen Urologie?

The da Vinci Surgical System represents a new technology in advanced laparoscopy: Sitting at a console that allows three-dimensional vision of the operating field, the robotic surgeon is enabled to perform complex laparoscopic procedures. The movements of telemanipulators ("masters") are transferred to EndoWrist instruments with all degrees of freedom. Compared with conventional laproscopy, the technology allows more dexterity, a shorter learning curve, improved vision, reduced operating time with reduced staff requirements, and an ergonomically designed work station with minimal burden on the back and joints. The following article describes the principles of this technology and the challenges of the capital investment and the running costs.

[Robot-assisted laparoscopic radical prostatectomy]. / Roboterassistierte laparoskopische Prostatektomie.

The advantage of minimally invasive surgery in the form of laproscopic radical prostatectomy compared with open retropubic radical prostatectomy is indisputable. But a long learning curve seems to be a clear disadvantage. Robotic surgery devices such as the da Vinci system could be very helpful here. The aim of this study was to demonstrate our own experience with da Vinci prostatectomy in consideration of the learning curve. Since implementation of the da Vinci system 23 months ago, we have done over 300 operating procedures with the system. Despite of having great know how in laparoscopic surgery the conversion rate was only 1.7%. The oncological outcome was satisfactory and comparable with the results reported in the literature. A complication rate of only 5.1% also seems acceptable. With the da Vinci system, we can combine the advantages of a minimally invasive procedure with those of open surgery but without the disadvantage of a long learning curve. At the moment, the expense factor remains a handicap.

[Robot-assisted laparoscopic radical cystectomy]. / Roboterassistierte laparoskopische radikale Zystektomie.

Recent reports have demonstrated that robot-assisted laparoscopic cystectomy is technically feasible. However, wide-spread acceptance of this promising technique is limited due to long operating times and lacking long-term data especially on oncological outcome. After establishing robot-assisted laparoscopic prostatectomy (n=250) we report technical and functional results of a large series of patients undergoing laparoscopic cystectomy with the da Vinci surgical system (DVSS).27 patients (24 males) underwent laparoscopic radical cystectomy with the DVSS (Intuitive Surgical) between Jan 2004 and Dec 2006. Indications for cystectomy were muscle-invasive transitional cell carcinoma (TCC) or leiomyosarcoma of the urinary bladder (n=24) and bladder shrinking following prior radiotherapy for TCC (n=3). A pelvic lymphadenectomy was routine part of the procedure. Urinary diversions were ilieal conduits (n=19) and ileal neobladders (n=8). Mean operating time was 340 minutes (range 150-450) with a mean blood loss of 301 mL (range 50-550). The mean number of lymph nodes retrieved during lymphadenectomy was 23. Surgical margins were negative except in one case. After a mean follow-up of 10.2 months, 2 perioperative (anastomotic leakage, adhesions) and 3 postoperative complications (ileus, intestinal fistula) occurred. 6/7 patients reported satisfying erectile function following nerve-sparing surgery. Day-time continence was completely restored after a mean 3.5 months in 7/8 patients.Robot-assisted laparoscopic cystectomy is a safe procedure. Satisfying functional and oncological short-term results can be achieved within acceptable operating time limits.

[Development of a three-dimensional primary prostate cancer cell culture model]. / Entwicklung eines dreidimensionalen Prostatakarzinomzellkulturmodells.

Much prostate cancer research is based on cell culture results. Recent genomic studies found major differences between primary prostate cancer tissue and established prostate cancer cell lines, which calls into question the clinical relevance of study results based on cell cultures.Using primary cultures of prostate cancer cells from prostatectomy specimens seems to be a reasonable solution, but primary cell cultures are much more difficult to establish. In this study, a primary cell culture model was combined with an invasion assay. With this combination it was possible not only to select invasive cell clones from the primary culture but also to culture these cells in a three-dimensional model, forming spheroids. A further characterization of this cell population was done by comparative genomic hybridization, showing numerous genetic alterations. The presented cell culture model offers, for the first time, an opportunity to isolate invasive growing cells from primary prostate cancer tissue and cultivate these cells for further analyses.

Survival outcomes in patients with large (≥7cm) clear cell renal cell carcinomas treated with nephron-sparing surgery versus radical nephrectomy: Results of a multicenter cohort with long-term follow-up.

BACKGROUND: Does the dogma of nephron sparing surgery (NSS) still stand for large renal masses? Available studies dealing with that issue are considerably biased often mixing imperative with elective indications for NSS and also including less malignant variants or even benign renal tumors. Here, we analyzed the oncological long-term outcomes of patients undergoing elective NSS or radical tumor nephrectomy (RN) for non-endophytic, large (≥7cm) clear cell renal carcinoma (ccRCC). METHODS: Prospectively acquired, clinical databases from two academic high-volume centers were screened for patients from 1980 to 2010. The query was strictly limited to patients with elective indications. Surgical complications were retrospectively assessed and classified using the Clavien-Dindo-classification system (CDS). Overall survival (OS) and cancer specific survival (CSS) were analyzed using the Kaplan-Meier-method and the log-rank test. RESULTS: Out of in total 8664 patients in the databases, 123 patients were identified (elective NSS (n = 18) or elective RN (n = 105)) for ≥7cm ccRCC. The median follow-up over all was 102 months (range 3-367 months). Compared to the RN group, the NSS group had a significantly longer median OS (p = 0.014) and median CSS (p = 0.04). CONCLUSIONS: In large renal masses, NSS can be performed safely with acceptable complication rates. In terms of long-term OS and CSS, NSS was at least not inferior to RN. Our findings suggest that NSS should also be performed in patients presenting with renal tumors ≥7cm whenever technically feasible. Limitations include its retrospective nature and the limited availability of data concerning long-term development of renal function in the two groups.

[Is there an indication for adjuvant or neoadjuvant systemic chemotherapy in bladder cancer?]. / Gibt es eine Indikation für eine adjuvante oder neoadjuvante Systemtherapie beim Blasenkarzinom?

Two recent meta-analyses demonstrated a significant influence of adjuvant as well as neoadjuvant cisplatin-based chemotherapy regimens on survival of patients undergoing radical cystectomy for bladder cancer. Therefore, the introductory question can be answered with "yes". However, while providing the best evidence available to date on the subject, both analyses are based on clinical trials of dubious quality. Thus, the question today is not whether perioperative chemotherapy is advantageous in some patients undergoing radical cystectomy, but rather which subgroups will actually benefit from additional systemic treatment. Instead of a detailed literature overview, this article discusses potential advantages and disadvantages of perioperative chemotherapy and outlines basic principles for the design of future studies investigating both strategies in bladder cancer.