INTRODUCTION & OBJECTIVES: It is currently recommended to perform open radical nephroureterectomy (oRNU) with bladder cuff excision in patients with locally advanced (cT3-4 or cN1-2) upper tract urothelial carcinoma (laUTUC). We tested the hypothesis that bladder recurrence-free survival (BRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) are not influenced by the surgical approach in patients with laUTUC using a large multicenter series. MATERIAL & METHODS: This was a multicenter retrospective cohort study including 361 patients with preoperative cT3-4 cM0 or cN1-2 cM0 laUTUC treated with open or minimally invasive RNU from 1999 to 2019 at 21 academic centers in Europe, Asia, and the United States. Missing values of relevant baseline characteristics were estimated through multiple imputation of chained equations. Baseline patients' heterogeneity was balanced using a 1:1 propensity score matching estimated using logistic regression. Uni- and multivariable Cox regression analyses for bladder recurrence, metastasis, cancer-specific death and overall death were performed according to clinical and pathological characteristics. Kaplan Meier (KM) estimates and log-rank test were used to compare BRFS, MFS, CSS and OS according to clinical and pathological features. RESULTS: Median follow-up was 28 months. After propensity score matching, two cohorts of 115 laUTUC patients each with similar baseline and preoperative tumor characteristics were obtained. In the matched cohort, pT ≥ 3 stage was found in 84 (73%) and 67 (58.3%) patients in the oRNU and miRNU groups, respectively. Positive lymph nodes were detected in 27 (23.5%) and 32 (27.8%) patients in the oRNU and miRNU groups, respectively. In the multivariable regression analysis, pT ≥ 3 and positive lymph nodes were associated with an increased risk of metastasis (HR 3.22, 95% CI 1.26-8.23, and HR 4.03, 95% CI 2.05-7.89, respectively). The surgical approach (oRNU vs. mi RNU) did not influence oncological outcomes as shown by uni- and multivariable analyses as well as Kaplan-Meier estimates, regardless of pT stage. CONCLUSIONS: The oncological outcomes of laUTUC for cT3-4 cM0 or cN1-2 cM0 disease are comparable whether RNU is performed via an open or minimally invasive approach. Therefore, the decision to opt for oRNU or miRNU should be guided by the surgeon's expertise and the patient's comorbidities, rather than concerns over long-term oncological outcomes associated with either surgical technique.

• Klíčová slova
• Locally advanced Utuc, Minimally-invasive nephroureterectomy, Open nephroureterectomy, Upper tract urothelial cancer, Utuc,
• MeSH
• karcinom z přechodných buněk * chirurgie   patologie   mortalita   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• miniinvazivní chirurgické výkony metody   MeSH
• míra přežití MeSH
• nádory ledvin * chirurgie   patologie   mortalita   MeSH
• nádory močovodu * chirurgie   patologie   mortalita   MeSH
• nefroureterektomie * metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH

INTRODUCTION: Platinum-based chemotherapy followed by the immune checkpoint inhibitor avelumab represents an intensified upfront therapy regimen that may result in significant downstaging and, subsequently, potentially radical robotic nephroureterectomy with a lymph node dissection, an uncommon approach with an unexpectedly favorable outcome. CASE PRESENTATION: We report a case of a 70-year-old female presented with a sizeable cN2+ tumor of the left renal pelvis and achieved deep partial radiologic response after systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance therapy and subsequent robotic resection of the tumor. The patient continued with adjuvant nivolumab therapy once recovered after surgery and remained tumor-free on the subsequent follow-up. The systemic treatment was without any severe adverse reaction. CONCLUSION: We highlight the feasibility of the upfront systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance, robotic-assisted removal of the tumor, and adjuvant immunotherapy with nivolumab. This intensification of the upfront systemic therapy, and the actual treatment sequence significantly increase the chances of prolonged survival or even a cure. This type of personalized therapeutic approach can accelerate future advanced immunotherapeutic strategies.

• Klíčová slova
• UTUC, cancer-specific survival, immune checkpoint inhibitors, immunotherapy, neoadjuvant chemotherapy, radical nephroureterectomy, upper urinary tract carcinoma,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

UNLABELLED: Early recognition of hereditary urological cancers may influence diagnostic and therapeutic decision-making, and potentially alter the fate of patients and family members. Here, we introduce readers to the current knowledge on germline genetic testing and clinical practice in prostate, bladder, renal, and testicular carcinoma. Considering all urological cancer patients, routine inquiries about familial cancer history should become a standard practice in clinical settings. If suspicion arises, patients can opt for two avenues: referral to genetic counseling or undergoing genetic tests after consultation with the treating urologist. PATIENT SUMMARY: Tumors of the urogenital tract (prostate, kidney, bladder, and testes) can sometimes be related to genetic mutations that are present in all the cells of the body. Such mutations can be inherited and run in families. Therefore, it is relevant to obtain information on the incidence of all cancers in the family history. The information obtained may initiate genetic testing, leading to the identification of mutations that are related to cancer in the current or next generation. In addition, these mutations may offer alternative treatment options for patients.

• Klíčová slova
• Genetic, Germline testing, Hereditary cancer, Prostate cancer, Renal cancer, Syndromes, Testicular cancer, Urothelial tract cancer,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care. OBJECTIVE: This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy. METHODS: The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. RESULTS: Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9-71.3) versus 20.8 (95% CI 12.6-24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31-0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1-40.5) and 13.0 months (95% CI 6.6-23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3-22.4) and 4.9 months (95% CI 3.0-8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively). CONCLUSIONS: Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management.

• MeSH
• cytoredukční chirurgie * metody   MeSH
• dospělí MeSH
• imunoterapie * metody   MeSH
• inhibitory proteinkinas * terapeutické užití   farmakologie   MeSH
• inhibitory tyrosinkinasy MeSH
• karcinom z renálních buněk * farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory ledvin * farmakoterapie   patologie   MeSH
• nefrektomie * metody   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory proteinkinas * MeSH
• inhibitory tyrosinkinasy MeSH

Non-metastatic upper urinary tract carcinoma (UTUC) is a comparatively rare condition, typically managed with either kidney-sparing surgery (KSS) or radical nephroureterectomy (RNU). Irrespective of the chosen therapeutic modality, patients with UTUC remain at risk of recurrence in the bladder; in patients treated with KSS, the risk of recurrence is high in the remnant ipsilateral upper tract system but there is a low but existent risk in the contralateral system as well as in the chest and in the abdomen/pelvis. For patients treated with RNU for high-risk UTUC, the risk of recurrence in the chest, abdomen, and pelvis, as well as the contralateral UT, depends on the tumor stage, grade, and nodal status. Hence, implementing a risk-stratified, location-specific follow-up is indicated to ensure timely detection of cancer recurrence. However, there are no data on the type and frequency/schedule of follow-up or on the impact of the recurrence type and site on outcomes; indeed, it is not well known whether imaging-detected asymptomatic recurrences confer a better outcome than recurrences detected due to symptoms/signs. Novel imaging techniques and more precise risk stratification methods based on time-dependent probabilistic events hold significant promise for making a cost-efficient individualized, patient-centered, outcomes-oriented follow-up strategy possible. We show and discuss the follow-up protocols of the major urologic societies.

• Klíčová slova
• follow-up, surveillance, upper tract urothelial carcinoma, urothelial carcinoma,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Upper tract urothelial carcinoma (UTUC) is the third most common malignancy associated with Lynch syndrome (LS). The current European urology guidelines recommend screening for LS in patients with UTUC up to the age of 60 years. In this study, we examined a cohort of patients with UTUC for potential association with LS in order to establish the sensitivity of current guidelines in detecting LS. A total of 180 patients with confirmed diagnosis of UTUC were enrolled in the study during a 12-year period (2010-2022). Loss of DNA-mismatch repair proteins (MMRp) expression was identified in 15/180 patients (8.3%). Germline analysis was eventually performed in 8 patients confirming LS in 5 patients (2.8%), including 4 germline mutations in MSH6 and 1 germline mutation in MSH2. LS-related UTUC included 3 females and 2 males, with a mean age of 66.2 years (median 71 years, range 46-75 years). Four of five LS patients (all with MSH6 mutation) were older than 65 years (mean age 71.3, median 72 years). Our findings indicate that LS-associated UTUCs can occur in patients with LS older than 60 years. In contrast to previous studies which used mainly highly pre-selected populations with already diagnosed LS, the most frequent mutation in our cohort involved MSH6 gene. All MSH6 mutation carriers were > 65 years, and UTUC was the first LS manifestation in 2/4 patients. Using current screening guidelines, a significant proportion of patients with LS-associated UTUC may be missed. We suggest universal immunohistochemical MMRp screening for all UTUCs, regardless of age and clinical history.

• Klíčová slova
• Immunohistochemistry, Lynch syndrome, MMR, Screening algorithm, Upper urinary tract, Urothelial carcinoma,
• MeSH
• dědičné nepolypózní kolorektální nádory * diagnóza   genetika   patologie   MeSH
• karcinom z přechodných buněk * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mismatch repair endonukleáza PMS2 genetika   MeSH
• MutL homolog 1 genetika   MeSH
• nádory močového měchýře * MeSH
• oprava chybného párování bází DNA MeSH
• senioři MeSH
• urologie * MeSH
• zárodečné mutace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mismatch repair endonukleáza PMS2 MeSH
• MutL homolog 1 MeSH

PURPOSE: To evaluate the prognostic value and the clinical impact of preoperative serum cholinesterase (ChoE) levels on decision-making in patients treated with radical nephroureterectomy (RNU) for clinically non-metastatic upper tract urothelial cancer (UTUC). METHODS: A retrospective review of an established multi-institutional UTUC database was performed. We evaluated preoperative ChoE as a continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with cancer-specific survival (CSS). We used univariable and multivariable Cox regression models to establish its association with recurrence-free survival (RFS), CSS, and overall survival (OS). Discrimination was evaluated using Harrell's concordance index. Decision curve analysis (DCA) was used to assess the impact on clinical decision-making of preoperative ChoE. RESULTS: A total of 748 patients were available for analysis. Within a median follow-up of 34 months (IQR 15-64), 191 patients experienced disease recurrence, and 257 died, with 165 dying of UTUC. The optimal ChoE cutoff identified was 5.8 U/l. ChoE as continuous variable was significantly associated with RFS (p < 0.001), OS (p < 0.001), and CSS (p < 0.001) on univariable and multivariable analyses. The concordance index improved by 8%, 4.4%, and 7% for RFS, OS, and CSS, respectively. On DCA, including ChoE did not improve the net benefit of standard prognostic models. CONCLUSION: Despite its independent association with RFS, OS, and CSS, preoperative serum ChoE has no impact on clinical decision-making. In future studies, ChoE should be investigated as part of the tumor microenvironment and assessed as part of predictive and prognostic models, specifically in the setting of immune checkpoint-inhibitor therapy.

• Klíčová slova
• Biomarker, Cholinesterase, Decision curve analysis, Upper urinary tract urothelial carcinoma, Urothelial neoplasm,
• MeSH
• cholinesterasy MeSH
• karcinom z přechodných buněk * patologie   MeSH
• lidé MeSH
• lokální recidiva nádoru chirurgie   MeSH
• močové ústrojí * MeSH
• nádorové mikroprostředí MeSH
• nefroureterektomie MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• urologické nádory * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholinesterasy MeSH