Treatment Patterns and Real-World Outcomes for Locally Advanced or Metastatic Urothelial Cancer in the Era of Immunotherapy.

BACKGROUND AND OBJECTIVE: There are limited data on real-world outcomes for patients with advanced or metastatic urothelial cancer (mUC) since immune checkpoint inhibitors (ICIs) became available. Our objective was to analyze outcomes for patients with mUC since ICIs became available. METHODS: We performed a retrospective analysis of 131 patients with mUC attending the outpatient clinic of a single tertiary care center who received systemic therapy between June 2017 and July 2021 with follow-up up to December 2022. Summary and descriptive statistics were calculated for categorical and continuous variables. The Kaplan-Meier method was applied to calculate survival, and a Cox proportional-hazards model was used to explore associations between clinical variables and outcomes. KEY FINDINGS AND LIMITATIONS: The median patient age was 68 yr (range 35-90). The first systemic therapy administered was platinum-based in 79% of cases and ICI-based in 21%. Some 61% of the cohort received a second systemic treatment, with 75% of these an ICI. Median overall survival for the entire cohort was 24 mo (interquartile range 9-35). Patients on ICI therapy for ≥6 mo had median overall survival of 59 mo (95% confidence interval 39 mo-not reached). Metastatic sites on initiation of ICI therapy and C-reactive protein kinetics were prognostic in patients receiving ICIs. Limitations include the retrospective design and inherent selection bias. CONCLUSIONS AND CLINICAL IMPLICATIONS: More than 60% of patients with mUC received second-line treatment, and 75% of these received an ICI. Patients staying on immunotherapy for more than 6 mo have substantially better outcomes in comparison to patients with less time on immunotherapy and historical cohorts. PATIENT SUMMARY: We looked at the lines of therapy and outcomes for patients with advanced or metastatic cancer of the urinary tract, starting from when immunotherapy drugs called immune checkpoint inhibitors (ICIs) became available. We found that 60% of patients have received second-line therapy, which is a double the rate in comparison to historical groups of patients. Patients with long-term ICI therapy (>6 months) had significantly better outcomes, with a median survival of more than 3 years.

Sarcopenia Predicts Disease Progression in Patients with T1 High-grade Non-muscle-invasive Bladder Cancer Treated with Adjuvant Intravesical Bacillus Calmette-Guérin: Implications for Decision-making?

Background: Skeletal muscle loss (sarcopenia) has been linked to cancer cachexia and can predict survival in several tumors, including advanced genitourinary malignancies. Objective: To investigate the predictive and prognostic role of sarcopenia in patients with T1 high grade (HG) non-muscle invasive bladder cancer (NMIBC) treated with adjuvant intravesical Bacillus Calmette-Guerin (BCG). Design setting and participants: Oncological outcomes were evaluated for 185 patients with T1 HG NMIBC treated with BCG at two European referral centers. Sarcopenia, identified from computed tomography scans performed within 2 mo after surgery, was defined as a skeletal muscle index of <39 cm2/m2 for women and <55 cm2/m2 for men. Outcome measurements and statistical analysis: The main endpoint was the association between sarcopenia and disease recurrence and progression. Kaplan-Meier curves and multivariable Cox models were built, and the clinical value of any association was assessed using Harrell's C index and decision curve analysis (DCA). Results and limitations: Sarcopenia was present in 130 patients (70%). On multivariable Cox regression analyses that accounted for the effect of standard clinicopathological prognosticators, sarcopenia was independently associated with disease progression (hazard ratio 3.41; p = 0.02). Addition of sarcopenia to a standard model for prediction of disease progression improved the discrimination of the model from 62% to 70%. DCA revealed superior net benefits for the proposed model in comparison to the strategies of treating all or no patients with radical cystectomy, and in comparison to the existing predictive model. Limitations are inherent to the retrospective design. Conclusions: We demonstrated the prognostic role of sarcopenia in T1 HG NMIBC. Pending external validation, this tool could be easily incorporated into existing nomograms for prediction of disease progression to improve clinical decision-making and patient counseling. Patient summary: We looked at the role of loss of skeletal muscle (sarcopenia) as a factor in predicting prognosis for stage T1 high-grade non-muscle-invasive bladder cancer. We found that sarcopenia is a ready-to-use, cost-free marker that could be used to guide treatment and follow-up in this disease, although the results need to be confirmed in other studies.

Impact of the preoperative modified Glasgow Prognostic Score on disease outcome after radical cystectomy for urothelial carcinoma of the bladder.

BACKGROUND: To investigate the predictive and prognostic value of the preoperative modified Glasgow Prognostic Score (mGPS) in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). METHODS: We conducted a retrospective analysis of an established multicenter database consisting of 4335 patients who were treated with RC±adjuvant chemotherapy for UCB between 1979 and 2012. The mGPS of each patient was calculated on the basis of preoperative serum C-reactive protein and albumin. Uni- and multivariable logistic and Cox regression analyses were performed. The discriminatory ability of the models was assessed by calculating the area under receiver operating characteristics curves (AUC) and concordance-indices (C-Index). The additional clinical net-benefit was assessed using the decision curve analysis (DCA). RESULTS: A mGPS of 0, 1, and 2 was observed in 3,158 (72.8%), 1,020 (23.5%), and 157 (3.6%) patients, respectively. On multivariable logistic regression analyses, mGPS of 1 or 2 were associated with an increased risk of pT3/4 disease at RC (OR 1.25, P=0.004 and OR 2.58, SP<0.001, respectively) and/or lymph node metastasis (OR 1.7, P<0.001 and OR 3.9, P<0.001, respectively). Addition of the mGPS to a predictive model based on preoperatively available variables improved its accuracy for prediction of lymph node metastasis (change of AUC +3.7%, P<0.001). On multivariable Cox regression analyses, mGPS of 1 or 2 remained associated with worse recurrence-free survival (HR 1.14, P=0.03 and HR 1.89 P<0.001, respectively), cancer-specific survival (HR 1.16, P=0.032 and HR 2.1, P<0.001, respectively) and overall survival (HR 1.5, P=0.007 and HR 1.92 P<0.001, respectively) compared to mGPS of 0. The additional discriminatory ability of the mGPS for prognosis of survival outcomes in separate models that included either established pre- or postoperative variables did not improve the C-Index by a prognostically relevant degree (change of C-Index <2% for all models). On DCA, the inclusion of the mGPS did not meaningfully improve the net-benefit for clinical decision-making regarding survival outcomes. CONCLUSIONS: We confirmed that an elevated mGPS is an independent risk factor for non-organ confined disease and poor survival outcomes in patients with UCB undergoing RC. However, the mGPS showed little value in improving the discriminatory ability of predictive and prognostic models that relied on either pre- or postoperative clinicopathological variables. The discriminatory ability of this biomarker in the age of immunotherapy warrants further evaluation.

[Locally advanced or oligometastatic bladder cancer-role of local treatment of the primary tumor and metastases]. / Lokal fortgeschrittene oder oligometastasierte Blasenkarzinome ­ Stellenwert der Lokaltherapie von Primärtumor und Metastasen.

BACKGROUND: Treatment of muscle invasive bladder cancer can be challenging since treatment is associated with significant side effects and complication rates-especially in patients who often present with relevant comorbidities. In the metastatic stage, the purpose of treatment is palliation, although the oligometastatic stage takes a distinct role. At this stage, treatment of the primary tumor can play a role, if metastasis can be treated locally in addition to systemic treatment, especially the evolving drug treatment landscape could also change long holding paradigms in the near future. OBJECTIVES: This review focuses on the influence of definitive treatment of the primary tumor in patients with oligometastatic urothelial bladder cancer. MATERIALS AND METHODS: Based on a literature search, the aim was to summarize data and give an overview on treatment of oligo-metastatic bladder cancer with focus on treatment of the primary tumor. Presented data derived mostly from retrospective studies and meta-analyses. CONCLUSION: Local treatment of the primary tumor in context of a multimodal therapy of lymph node metastatic or oligometastatic bladder cancer can have a positive influence on survival, quality of life and prevention of local complications in selected patients. The choice of local treatment should follow the same criteria as in non-metastatic bladder cancer.

Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr-Sep) and an increase during the winter months (Oct-Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec (p = 0.008) and Jan-Mar (p < 0.001) was significantly higher compared to the months of Jul-Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.

Update on systemic treatment of upper tract urothelial carcinoma: a narrative review of the literature.

Urothelial cancer (UC) is most commonly found in the urinary bladder, but can also appear in the upper urinary tract, where it is associated with several disease-specific challenges affecting its diagnosis, clinical staging, surgical management, and systemic therapy. A significant number of patients experience extra-vesical disease recurrence despite radical nephroureterectomy (RNU), leading to inevitable demise. Over the last years, the therapeutic armamentarium of UC has expanded with several systemic treatment options entering clinical care and deliver the potential to support a more individualized treatment in the near future. Currently, novel targeted therapies are emerging, accompanied with extensive biomarker research, which leads to a better understanding of the disease and therefore, reshaping the treatment landscape continuously and decisively. Though, systemic treatment of UTUC comes along with certain challenges that are specific to the disease, e.g., loss of renal function after RNU, which might result in ineligibility for a cisplatin-based chemotherapy. In this narrative review, the current standard of systemic treatment of UC in the perioperative and metastatic treatment setting are reported, with focus on UTUC. In addition, molecular aspects of UTUC, as well as future directions and specific implications for treatment of patients diagnosed with UTUC are discussed.

Stratification of Intermediate-risk Non-muscle-invasive Bladder Cancer Patients: Implications for Adjuvant Therapies.

BACKGROUND: There is an urgent need to provide a risk-stratification tool for intermediate-risk non-muscle-invasive bladder cancer (NMIBC), especially at the time of bacillus Calmette-Guerin (BCG) shortage. OBJECTIVE: To assess whether patients with intermediate-risk NMIBC can be stratified into different risk groups, thereby providing a practical tool for the selection of the optimal adjuvant therapy, based on the individualized risk of disease progression. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of 636 patients with intermediate-risk NMIBC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariable Cox-regression model was built to evaluate the impact of each variable on recurrence and progression to muscle-invasive disease. A Cox-based nomogram to predict patient-specific probability of disease progression was performed, and the decision curve analysis (DCA) was used to evaluate its clinical benefit. RESULTS AND LIMITATIONS: Within a median follow-up of 92 mo (interquartile range 56-118), disease recurrence and progression occurred in 346 (54%) and 91 (14%) patients, respectively. On multivariable analysis, age, early recurrence (<12 mo), and tumor size≥3cm were found to be independent predictors of progression. The Harrell C-index of the model for the prediction of progression was 0.75 and exceeded that of the model proposed by the International Bladder Consultation Group. DCA showed superior net benefits for the nomogram compared with the strategies of treating all/none and previous predictive models. Limitations are inherent to the retrospective design. CONCLUSIONS: We provided a risk-stratification tool that helps identify individual risk of disease progression in patients with intermediate-risk NMIBC. This tool outperforms standard strategies in the threshold probability range of interest and could help select the optimal intravesical therapy regimen based on the individual risk of disease progression. PATIENT SUMMARY: In this study, we provided a practical tool for risk stratification in patients with intermediate-risk non-muscle-invasive bladder cancer. This tool may help select the most appropriate adjuvant therapy (either bacillus Calmette-Guerin [BCG] or chemotherapy) based on patient and tumor characteristics, thus making a step forward toward the era of personalized medicine.

The Predictive Value of Programmed Death Ligand 1 in Patients with Metastatic Renal Cell Carcinoma Treated with Immune-checkpoint Inhibitors: A Systematic Review and Meta-analysis.

CONTEXT: Immune-checkpoint inhibitors (ICIs) are a mainstay treatment of metastatic renal cell carcinoma (mRCC). As not all patients benefit from ICIs, a biomarker-driven clinical decision-making strategy is desirable. OBJECTIVE: To assess the predictive value of programmed death ligand 1 (PD-L1) in mRCC patients treated with ICIs. EVIDENCE ACQUISITION: Multiple databases were searched for articles published up to April 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies comparing objective response rate (ORR), complete response rate (CRR), progressive disease rate (PDR), or progression-free survival (PFS) based on tumor PD-L1 status in mRCC patients were eligible. EVIDENCE SYNTHESIS: Six studies matched our eligibility criteria. Treatment with ICIs was associated with significantly higher ORRs and CRRs, and lower PDRs in patients with PD-L1-positive tumors than in those with PD-L1-negative status (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.48-2.28; OR 3.11, 95% CI 2.04-4.75; and OR 0.43, 95% CI 0.31-0.60, respectively). ICI treatment was associated with significantly better PFS in PD-L1-positive patients than in sunitinib-treated patients (hazard ratio 0.65, 95% CI 0.57-0.74), whereas this was not found in patients with PD-L1-negative tumors. Compared with sunitinib, ICI combination therapy improved ORRs and PFS significantly in PD-L1-positive patients of all examined ICIs. Nivolumab plus ipilimumab had the highest likelihood of providing the highest ORR and longest PFS in PD-L1-positive patients. CONCLUSIONS: PD-L1 positivity of the tumor is associated with improved ORRs and prolonged PFS in mRCC patients receiving ICI treatment and thus helps identify mRCC patients most likely to benefit from ICI treatment. PATIENT SUMMARY: The use of an immune-checkpoint inhibitor for the treatment of metastatic renal cell carcinoma (mRCC) improved oncological outcomes, and the status of programmed death ligand 1 could contribute to guiding patients and clinicians when determining personalized treatment strategies for mRCC.

Immune checkpoint inhibition in muscle-invasive and locally advanced bladder cancer.

PURPOSE OF REVIEW: Immune-checkpoint inhibitors (CPIs) have been implemented in the treatment algorithm of metastatic urothelial cancer as they have shown higher and more sustained responses compared with conventional second-line chemotherapy. Recently, several clinical trials have reported on CPIs in earlier disease stages such as muscle-invasive bladder cancer (MIBC). This review summarizes ongoing clinical trials and results from early phase clinical trials in muscle invasive and locally advanced bladder cancer. RECENT FINDINGS: In phase II clinical trials, neoadjuvant use of CPIs as mono and combination therapy, in patients with MIBC planned for radical cystectomy, has shown promising pathological complete response rates. Whether this will translate in survival benefit remains to be assessed. Combination of CPIs and conventional chemotherapy or other targeted agents promises to increase the efficacy of perioperative systemic therapy with potentially additive toxicities. Recently, preclinical models of combined trimodal therapy with CPIs delivered the proof of principle leading to several ongoing trials in this setting. SUMMARY: First results of clinical trials evaluating CPIs in MIBC demonstrate very promising results that warrant further investigation as they could revolutionize management of MIBC in the near future. The trend and hope are toward higher rates of safe and sustained bladder preservation.

The role of taxane-based chemotherapy in the treatment of prostate cancer.

PURPOSE OF REVIEW: Indications for chemotherapy have increased in prostate cancer (PCA), many of which are shared with new hormonal agents (NHA). With no head to head comparison available, defining the optimal sequence and identifying biomarkers to predict response, has been a focus of intense research in PCA. We aim to summarize the best currently available evidence in all stages of disease to help guide therapy. RECENT FINDINGS: In metastatic castration-resistant prostate cancer, Cabazitaxel has shown improved radiographic progression-free survival over another NHA after Docetaxel and one NHA. For hormone sensitive PCA (mHSPC) multiple meta-analyses have shown combination therapy with Docetaxel or an NHA to be superior to androgen deprivation therapy alone, yet no clear benefit over each other. For peri-interventional chemotherapy with local therapy, there is currently only one positive prospective trial, for very high-risk disease. SUMMARY: Cabazitaxel is underutilized and should be used earlier. NHAs should not be used in succession as there is significant cross resistance. Combination therapy should be used in mHSPC, yet there is no clear benefit for any combination. Peri-interventional chemotherapy might have a benefit for a small group of patients with very high-risk disease, yet this must be carefully evaluated, and side effects must be taken into account.

Frontiers in combining immune checkpoint inhibitors for advanced urothelial cancer management.

PURPOSE OF REVIEW: This review provides an overview of currently ongoing clinical trials evaluating the combination of immune checkpoint inhibitors (CPI) with other therapies in locally advanced or metastatic urothelial cancer and the rationale for this combination approach. We discuss the preliminary results from early data presented at recent meetings regarding the efficacy and safety of novel combination therapies including a CPI for metastatic urothelial cancer. RECENT FINDINGS: CPI emerged as novel first-line or second-line treatment options in advanced and metastatic urothelial cancer (mUC). Although the response rates and their sustainability are promising, it is far from a home run. Combination therapies have already shown improved efficacy in several other tumor entities. SUMMARY: Numerous clinical trials currently investigate combinations of CPI with other CPI, previously established systemic chemotherapy, targeted therapies, vaccines, or accompanied with radiotherapy. Preliminary data shows promising results. These results suggest that targeting pathways of immune response combined with established or novel oncological therapies may lead to a synergistic antitumor effect.

Management of bladder cancer in older patients: Position paper of a SIOG Task Force.

Median age at bladder cancer (BC) diagnosis is older than for other major tumours. Age should not determine treatment, and patients should be fully involved in decisions. Patients should be screened with Mini-Cog™ for cognitive impairment and the G8 to ascertain need for comprehensive geriatric assessment. In non-muscle invasive disease, older adult patients should have standard therapy. Age does not contraindicate intravesical therapy. Independent of age and fitness, patients with muscle-invasive BC should have at least cross-sectional imaging. Data suggest extensive undertreatment in older adult patients, leading to poor outcomes. Standard treatment for a fit patient differs between countries. Radical cystectomy and trimodality therapy are first-line options. Radical cystectomy patients should be referred to an experienced centre and prehabilitation is mandatory. Older adult patients should be considered for neoadjuvant and adjuvant therapy, according to guidelines. In urinary diversion, avoiding bowel surgery for reconstruction of the lower urinary tract significantly reduces complications. If a patient is unfit for or refuses standard treatment, RT alone, or TURBT in selected cases should be considered. In metastatic BC, older adult patients should receive standard systemic therapy, depending on fitness for cisplatin and prognosis. Efficacy and tolerability of immunotherapy (IO) appears similar to younger patients. Second line IO is standard in platinum pre-treated patients, with benefit and tolerability in the older adult similar to younger patients. The toxicity profile seems to favour IO in the older adult but more data are needed. Patients progressing on IO may respond to further systemic treatment. In metastatic disease, palliative care should begin early.

Prognostic value of the systemic inflammation modified Glasgow prognostic score in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy: Results from a large multicenter international collaboration.

INTRODUCTION AND OBJECTIVES: To evaluate the prognostic role of modified Glasgow prognostic score (mGPS) for the prediction of oncological outcomes in a retrospective large multicenter cohort of upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed a multicenter cohort of patients treated with RNU for clinically nonmetastatic UTUC. Multivariable logistic regression analyses were performed to evaluate the ability of mGPS to predict nonorgan confined (NOC) disease and lymph-node involvement (LNI) at RNU. Multivariable Cox-regression models were performed to evaluate the preoperative and postoperative prognostic effect of mGPS on survival outcomes. RESULTS: Overall, 2,492 patients were included in the study. Of these, 1,929 (77%), 530 (21%), and 33 (1%) had a mGPS of 0, 1, and 2, respectively. mGPS was associated with characteristics of tumor aggressiveness and independently predicted LNI and NOC at RNU (both P < 0.05). On univariable and multivariable Cox-regression analyses, higher mGPS was independently associated with recurrence-free, cancer-specific, and overall survival, both in a preoperative and in a postoperative setting. The inclusion of mGPS significantly improved the discrimination of a preoperative model for the prediction of oncologic outcomes compared to standard prognosticators. CONCLUSIONS: We found that mGPS is independently associated with clinicopathologic features and survival outcomes after RNU. Future studies should investigate the role of mGPS in a panel of preoperative markers for the prediction of NOC and LNI in UTUC patients, thus possibly improving the selection for perioperative systemic therapy.

Comparative effectiveness of radical cystectomy and radiotherapy without chemotherapy in frail patients with bladder cancer.

Objectives: To evaluate cancer-specific (CSS) and overall survival (OS) in a group of frail patients who were treated with RT without chemotherapy and to compare them with a matched cohort of patients treated with RC.Methods: This study identified 71 patients treated with RT only for high-risk bladder cancer. Patients with metastatic (cN + or cM+) or non-resectable tumors (cT4) and those who received any form of chemotherapy were excluded. Patients where matched 1:1 using propensity scores which adjusted for the effects of age, clinical stage and age-adjusted Charlson comorbidity index (CCI). OS and CSS were evaluated using the Cox proportional hazards regression model and the Fine and Gray competing risk model.Results: In the overall population, RT was associated with worse OS (HR = 1.78, 95% CI = 1.15-2.77, p = 0.01) compared to RC, but not with CSS (HR 1.1, p = 0.74). In the matched cohort, RT was neither associated with OS nor CSS (p > 0.05) compared to RC. In the competing risk analyses no statistically significant association of any of the treatments was observed in the total or in the matched data set (p > 0.05).Conclusion: The use of RT may be an alternative option in well selected patients with limited disease who are considered unfit for systemic chemotherapy and RC. Future research should focus on improving patient selection and assess the quality-of-life as well as the need for reintervention in patients treated with RT.

Impact of Patients' Gender on Efficacy of Immunotherapy in Patients With Metastatic Kidney Cancer: A Systematic Review and Meta-analysis.

Recent meta-analyses on checkpoint inhibitors in cancer report conflicting data regarding the association of patient gender with inhibitor efficacy. In advanced kidney cancer, checkpoint inhibitors have shown improved outcomes in first- and second-line settings compared with standard of care, but the role of patient gender on treatment outcome is unclear. We aimed to assess the efficacy of immunotherapy according to patient gender in advanced kidney cancer. We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed using PubMed, Scopus, Web of Science, and The Cochrane Library to identify eligible studies published through February 16, 2019. Studies were included if they reported on the differential outcomes of male and female patients with metastatic kidney cancer receiving immunotherapy. Our outcomes of interest were overall survival (OS) or progression-free survival (PFS). Four randomized controlled trials comprising a total of 3664 patients (2715 males and 949 females) met our inclusion criteria. Both men and women with metastatic kidney cancer had an OS and PFS advantage with immunotherapy compared with standard-of-care, but no statistically significant difference between the genders was observed (OS hazard ratio [HR] for men, 0.69; 95% confidence interval [CI], 0.59-0.8; P = .40; HR for women, 0.62; 95% CI, 0.48-0.81; P = .13; PFS HR for men, 0.7; 95% CI, 0.59-0.82; P = .24; HR for women, 0.68; 95% CI, 0.52-0.90; P = .105). In patients with advanced kidney cancer receiving checkpoint inhibitors, there seems to be no association of patient gender with treatment outcome.

Association of super-extended lymphadenectomy at radical cystectomy with perioperative complications and re-hospitalization.

PURPOSE: We performed a retrospective analysis of patients treated with radical cystectomy and lymphadenectomy (LAD) for bladder cancer to assess the differential association of the extent of LAD with perioperative complications and re-hospitalization. MATERIALS AND METHODS: LAD templates were defined as limited (lLAD = external, internal iliac and obturator), extended (eLAD = up to crossing of ureter and presacral lymph nodes), and super-extended (sLAD = up to the inferior mesenteric artery). Logistic regression models investigated the association of LAD templates with intraoperative, 30- and 30-90-day postoperative complications, as well as re-hospitalizations within 30 and 30-90 days. RESULTS: A total of 284 patients were available for analysis. sLAD led to a higher lymph-node yield (median 39 vs 13 for lLAD and 31 for eLAD, p < 0.05) and N2/N3 status compared to lLAD and eLAD (p = 0.04). sLAD was associated with a blood loss of > 500 ml (OR 1.3, 95% CI 1.08-1.49, p = 0.003) but not with intraoperative transfusion, operation time, or length of hospital stay (p > 0.05). Overall, 11 (4%) patients were readmitted within 30 days and 50 (17.6%) within 30-90 days. The 30- and 30-90-day mortality rates were 2.8% and 1.4%, respectively. On logistic regression, LAD template was not associated with postoperative complications or re-hospitalization rates. CONCLUSIONS: sLAD leads to higher lymph-node yield and N2/N3 rate but not to higher complication rate compared to lLAD and eLAD. With the advent of novel adjuvant systemic therapies, precise nodal staging will have a crucial role in patients counseling and clinical decision making.