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Simple Summary: This research investigates whether a diagnostic technique called ureteroscopy (URS), performed before surgery for removing the kidney and ureter, influences the likelihood of cancer recurrence in the bladder in patients with upper tract urothelial carcinoma (UTUC). Data from a multicentre international registry were analysed to compare patients who underwent URS before their surgery with those who did not. The study found that patients who had URS prior to surgery experienced a higher rate of cancer recurrence in the bladder. These results highlight the need for careful consideration of the use of URS in the diagnostic process for UTUC, as it could affect long-term outcomes. This information is crucial for clinicians in optimizing treatment strategies and improving patient care. (1) Introduction: Diagnostic ureteroscopy (URS) is an important component in the workup of upper tract urothelial carcinoma (UTUC). Whether URS was associated with increased recurrence in the bladder was not fully concluded. The current study aimed to evaluate the implication of URS on the incidences of intravesical recurrence following radical nephroureterectomy (RNU) in non-metastatic UTUC patients without prior history of bladder cancer via multi-institutional data. (2) Patients and Methods: Data were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) registry, a prospective, multicentre database. Patients with non-metastatic UTUC treated with RNU were divided into two groups: those undergoing upfront RNU and those having diagnostic URS prior to RNU. Intravesical recurrence-free survival (IVRS) was the primary endpoint, evaluated through Kaplan–Meier analysis and multivariate Cox regression. Cases with adequate follow-up data were included. (3) Results: The analysis included 269 patients. Of these, 137 (50.9%) received upfront RNU and 132 (49.1%) received pre-RNU URS. The URS group exhibited an inferior 24-month IVRS compared to the upfront RNU group (HR = 1.705, 95% CI = 1.082–2.688; p = 0.020). Multivariate analysis confirmed URS as the only significant predictor of IVR (p = 0.019). Ureteric access sheath usage, flexible ureteroscopy, ureteric biopsy, retrograde contrast studies, and the duration of URS did not significantly affect IVRS. (4) Conclusions: Diagnostic URS prior to RNU was found to be associated with an increased risk of IVR in patients with UTUC. The risk was not significantly influenced by auxiliary procedures during URS. Physicians were advised to meticulously evaluate the necessity of diagnostic URS. [ABSTRACT FROM AUTHOR]

Radical cystectomy (RC) remains a mainstay surgical treatment for non-metastatic muscle-invasive and BCG-unresponsive bladder cancer. Various perioperative scoring tools assess comorbidity burden, complication risks, and cancer-specific mortality (CSM) risk. We investigated the prognostic value of these scores in patients who underwent RC between 2015 and 2021. Cox proportional hazards were used in survival analyses. Risk models' accuracy was assessed with the concordance index (C-index) and area under the curve. Among 215 included RC patients, 63 (29.3%) died, including 53 (24.7%) cancer-specific deaths, with a median follow-up of 39 months. The AJCC system, COBRA score, and Charlson comorbidity index (CCI) predicted CSM with low accuracy (C-index: 0.66, 0.65; 0.59, respectively). Multivariable Cox regression identified the AJCC system and CCI > 5 as significant CSM predictors. Additional factors included the extent of lymph node dissection, histology, smoking, presence of concomitant CIS, and neutrophil-to-lymphocyte ratio, and model accuracy was high (C-index: 0.80). The internal validation of the model with bootstrap samples revealed its slight optimism of 0.06. In conclusion, the accuracy of the AJCC staging system in the prediction of CSM is low and can be improved with the inclusion of other pathological data, CCI, smoking history and inflammatory indices. [ABSTRACT FROM AUTHOR]

Background and Objectives: Renal cell carcinomas and upper tract urothelial carcinomas are types of malignancies that originate in the kidneys. Each of these examples shows an increasing trend in the frequency and the mortality rate. This study aims to comprehensively define carcinomas by analyzing clinical, paraclinical, and histological aspects to predict aggressiveness and mortality. Materials and Methods: We conducted a retrospective investigation on a group of patients suspected of kidney cancers. Results: We identified 188 cases. We observed a higher mortality rate and older age in individuals with urothelial carcinomas. Anemia, acute kidney injury, hematuria, and perineural invasion were the main risk factors that predicted their mortality. Tumor size in renal cell carcinomas correlates with the presence of necrosis and sarcomatoid areas. Factors that indicate a higher rate of death are older age, exceeding the renal capsule, a lesion that includes the entire kidney, lymphovascular invasion, acute kidney injury, and anemia. Conclusions: Even if they originate at the renal level, and the clinical–paraclinical picture is similar, the histopathological characteristics make the difference. In addition, to these are added the previously mentioned common parameters that can represent important prognostic factors. In conclusion, the characteristics commonly identified in one type of cancer may act as risk factors for the other tumor. The detected data include threshold values and risk factors, making a significant contribution to the existing literature. [ABSTRACT FROM AUTHOR]

Background: To conduct a comprehensive systematic review and network meta-analysis of RCTs that compare outcomes of robot-assisted radical cystectomy (RARC) with intra- or extracorporeal urinary diversion (ICUD or ECUD) and the standard open approach (oRC). Methods: A systematic review identified RCTs including patients aged >18 years with non-metastatic bladder cancer treated with RARC (ICUD or ECUD) vs. oRC and reporting peri- and post-operative outcomes and quality of life (QoL) assessment. Standard and network metanalyses were performed. Results: Data from 1024 patients included in eight RCTs were analyzed. The standard meta-analysis found that RARC had longer OT, lower EBL, and a lower transfusion rate compared to oRC (all p < 0.001). No significant differences in terms of LOS between the ICUD vs. ECUD vs. ORC were recorded. RARC patients demonstrated better scores in fatigue, insomnia, pain, physical functioning, and role functioning—according to QoL assessment—compared to ORC at early follow-up, despite no difference at baselines. Finally, at network metanalysis, ICUD (OR = 0.74, p < 0.001) but not ECUD (OR = 0.92, p < 0.08) yielded a lower rate of high-grade 90-day complications compared to ORC despite longer OT (MD = 89.56, p = 0.0351). Conclusions: RARC represents a safe and feasible option to reduce perioperative bleeding with no definitive impact on LOS compared to ORC. Interestingly, ICUD may reduce the burden of 90-day complications to a greater extent than ECUD. Nonetheless, surgeons should be aware of the extended OT and steep learning curve of ICUD. Finally, RARC may provide some short-term benefits in terms of QoL, but more research is needed to determine its long-term effects. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is one of the most prevalent cancers worldwide. Non-muscle invasive bladder cancer (NMIBC), comprising the majority of initial BC presentations, requires accurate risk stratification for optimal management. This review explores the evolving role of programmed cell death ligand 1 (PD-L1) as a prognostic biomarker in NMIBC, with a particular focus on its implications in the context of Bacillus Calmette-Guérin (BCG) immunotherapy. The literature suggests a potential association between elevated PD-L1 status and adverse outcomes, resistance to BCG treatment, and disease progression. However, conflicting findings and methodological issues highlight the heterogeneity of PD-L1 assessment in NMIBC, probably due to the complex biological mechanisms that regulate the interaction between PD-L1 and the tumor microenvironment. The identification of PD-L1 as a prognostic biomarker provides ground for tailored therapeutic interventions, including immune checkpoint inhibitors (ICIs). Nevertheless, challenges such as intratumoral heterogeneity and technical issues underscore the need for standardized protocols and larger, homogeneous trials. This review contributes to the ongoing debate on the personalized management of NMIBC patients, focusing on the advances and perspectives of incorporating PD-L1 as a biomarker in this setting. [ABSTRACT FROM AUTHOR]

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10–15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10–15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of immuno-oncology in various hematologic and solid malignancies offers new targets with tremendous therapeutic potential in UC. Historically, there were no predictive biomarkers to guide the clinical management and treatment of UC, and biomarker development was an unmet need. However, recent and ongoing clinical trials have identified several promising tumor biomarkers that have the potential to serve as predictive or prognostic tools in UC. This review provides a comprehensive summary of emerging biomarkers and molecular tumor targets including programmed death ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor (FGFR), DNA damage response and repair (DDR) mutations, poly (ADP-ribose) polymerase (PARP) expression and circulating tumor DNA (ctDNA), as well as their clinical utility in UC. We also evaluate recent advancements in precision oncology in UC, while illustrating limiting factors and challenges related to the clinical application of these biomarkers in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is the sixth most common cancer in the world. With 73 years, bladder cancer has the highest age-at-diagnosis of all cancers. While the surgical removal of the bladder remains the standard-of-care treatment for advanced muscle-invasive disease, around half of patients still metastasize. Then, platinum-based chemotherapy is recommended as the first-line treatment. However, only about half of those patients are eligible to receive chemotherapy, and novel immune-checkpoint inhibitors are restricted to biomarker (PD-L1)-positive patients. In our study, we demonstrate that PD-L1-positive patients show slower progression. However, there is no benefit in overall survival, emphasizing the need for novel and more reliable biomarkers in the future. Background: Our study endeavors to elucidate the clinical implications of PD-L1 positivity in individuals afflicted with advanced urothelial carcinoma of the bladder (UCB). Methods: Patients with advanced UCB were prospectively enrolled following a radical cystectomy (RC) performed within January 2017 to December 2022 at our tertiary referral center. The clinical outcome, defined as the progression-free survival (PFS) and overall survival (OS) on systemic treatment, was analyzed using an χ2-test, Mann–Whitney U-test, the Kaplan–Meier method, and a log-rank test. Results: A total of 648 patients were included following an RC performed within January 2017 to December 2022. Their PD-L1 status was analyzed with the primary PD-L1-specific antibody (clone SP263, Ventana) and defined both by the CPS and IC-score in 282 patients (43.5%) with a high risk (pT3–pT4 and/or lymph node involvement) or metastatic UCB. While the median PFS was significantly prolonged 5-fold in PD-L1+ patients, we found no difference in OS, regardless of PD-L1 status, or treatment regimen. Conclusions: While PD-L1 positivity indicates prolonged PFS, the presence of PD-L1 does not influence OS rates, suggesting its limited usefulness as a prognostic biomarker in bladder cancer. However, the positive correlation between an PD-L1 status and a sustained response to ICI treatments indicates its potential role as a predictive biomarker. Further research is required to understand how the predictive value of PD-L1 positivity may extend to the use of ICIs in combination with antibody-drug conjugates. [ABSTRACT FROM AUTHOR]

Background: The incidence of upper tract urothelial carcinoma (UTUC) is uniquely high in kidney transplant (KT) recipients in Taiwan. The evidence of adjuvant chemotherapy (AC) in UTUC is contradictory. We have sought to determine whether AC is associated with potential benefits related to locally advanced UTUC after KT. Methods: We retrospectively analyzed 134 patients with locally advanced UTUC (at least stage T2) and patients who were administrated AC after unilateral or bilateral nephroureterectomy with bladder cuff excision. Of these 134 patients, 57 patients fulfilled our inclusion criteria. We used 23 KT and 34 non-KT locally advanced UTUC patients for comparison. Results: The mean follow-up time was 52.35 ± 34.56 and 64.71 ± 42.29 months for the KT and non-KT groups, respectively. The five-year disease-free survival (DFS) and overall survival (OS) rates were 45.7% vs. 70.2% and 62.8% vs. 77.6%, for the KT and non-KT groups. The Kaplan–Meier curve and the log rank test revealed significant differences in the DFS and OS rates between the two groups, p = 0.015 and 0.036. The influence of chemotherapy on graft kidney function was mild. Only three in the KT group and two in the non-KT group developed > grade 2 nephrotoxicity. Conclusions: Our study suggested that KT patients with locally advanced UTUC who had been administered AC after surgery presented worse OS and DFS than non-KT patients. KT patients tolerated the AC course well, and their nephrotoxicity levels were mild and acceptable. [ABSTRACT FROM AUTHOR]

The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: While immunotherapy with checkpoint inhibitors is a standard component of treatment for advanced bladder cancer, its potential in early-stage, non-muscle-invasive bladder cancer (NMIBC) is increasingly being evaluated. Traditionally, NMIBC is managed with Bacillus Calmette–Guérin (BCG), a therapy that activates the immune system. Given that PD-L1 protein expression is an important marker for predicting the response to immunotherapy in advanced stages, and has shown prognostic value, and considering that BCG therapy functions by stimulating the immune system, our aim is to investigate whether PD-L1 levels change over time or with BCG treatment in high-risk NMIBC patients, and the prognostic implications thereof. This research could offer new insights into biomarker expression in early-stage bladder cancer by evaluating its susceptibility to therapies. The capacity of BCG to influence PD-L1 expression might provide hints for a sequential application of therapies. In the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacillus Calmette–Guérin (BCG) therapy in HR NMIBC patients is scarce. This retrospective study analyzed 126 HR NMIBC tissue samples from 63 patients (38× BCG-treated, 25× BCG-naïve) at two time points to assess PD-L1 expression using the 'combined positivity score' (CPS) with the 22C3 DAKO antibody method and correlated it with clinicopathological parameters. A CPS > 10 defined PD-L1 positivity. The impact of initial PD-L1 status and its change over time on time-to-recurrence, progression-free survival, and overall survival (TTR, PFS, OS) was analyzed using Kaplan–Meier and Cox proportional hazard models. BCG treatment significantly increased PD-L1 expression (5.31 vs. 0.22, p = 0.0423), with PD-L1 positive cases rising post-treatment in the BCG group and remaining unchanged in BCG-naïve patients. Multivariate analysis including T-stage, CIS, grading, tumor size, multifocality, age, and sex revealed a significant correlation between PD-L1 status change to positivity and improved TTR (p = 0.03). Our findings demonstrate a potential modulation of the PD-L1 status by an intravesical BCG therapy. However, its prognostic value appears limited. [ABSTRACT FROM AUTHOR]

Simple Summary: The creation of a guideline of guidelines could help physicians apprehend different approaches to malignancies and better-tailoring patients' management. In this context, international guidelines on upper tract urothelial carcinoma (UTUC) have previously never been compared in their similarities and differences. The present effort could guide further researchers to provide more high-quality evidence to homogeneously assess, treat, and follow up patients affected by UTUC worldwide. Moreover, by highlighting similarities and differences, we aim to encourage more conscious and critical use of guidelines and push research to fill knowledge gaps. Background: Upper tract urothelial carcinoma (UTUC) is a rare disease with a potentially dismal prognosis. We systematically compared international guidelines on UTUC to analyze similitudes and differences among them. Methods: We conducted a search on MEDLINE/PubMed for guidelines related to UTUC from 2010 to the present. In addition, we manually explored the websites of urological and oncological societies and journals to identify pertinent guidelines. We also assessed recommendations from the International Bladder Cancer Network, the Canadian Urological Association, the European Society for Medical Oncology, and the International Consultation on Bladder Cancer, considering their expertise and experience in the field. Results: Among all the sources, only the American Urologist Association (AUA), European Association of Urology (EAU), and the National Comprehensive Cancer Network (NCCN) guidelines specifically report data on diagnosis, treatment, and follow-up of UTUC. Current analysis reveals several differences between all three sources on diagnostic work-up, patient management, and follow-up. Among all, AUA and EAU guidelines show more detailed indications. Conclusions: Despite the growing incidence of UTUC, only AUA, EAU, and NCCN guidelines deal with this cancer. Our research depicted high variability in reporting recommendations and opinions. In this regard, we encourage further higher-quality research to gain evidence creating higher grade consensus between guidelines. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is a common diagnosis, of which a notable portion of patients present with an extension into the venous circulation causing an inferior vena cava (IVC) tumor thrombus. Venous extension has significant implications for staging and subsequent treatment planning, with recommendations for more aggressive surgical removal, although associated surgical morbidity and mortality is relatively increased. The methods for surgical removal of RCC with IVC thrombus remain complex, particularly surrounding the use of robot-assisted surgery. Robot assistance for radical nephrectomy in this context is recently emerging. Thrombus level has important implications for surgical technique and prognosis. Other preoperative considerations may include location, laterality, size, and wall invasion. The urology literature on treatment of such tumors is largely limited to case series and institutional studies that describe the feasibility of various surgical options for these complex tumors. Further understanding of the outcomes and patient-specific risk factors would shed increased light on the optimal treatment for such cases. This narrative review provides a thorough overview on the previously reported use of robot-assisted nephrectomy in RCC with IVC thrombus to inform further studies which may optimize outcomes and guide shared decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the efficacy of complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) during the tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) era. Analyzing data from a multi-institutional database with 367 mRCC patients, the CM group exhibited significantly longer overall survival than the non-CM group in unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35–0.69). However, this superiority was not sustained in adjusted cohorts. The median disease-free survival (DFS) after CM was 24 months, with no significant differences noted based on the time of relapse. This study supports CM's potential in mRCC management during the TKI/ICI era, acknowledging limitations such as sample size and selection bias. Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35–0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered. [ABSTRACT FROM AUTHOR]

Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of patients with SUC treated with EV for metastatic disease. We retrospectively evaluated consecutive patients with advanced lower and upper urinary tract cancer who received EV after platinum-based chemotherapy and immune checkpoint blockade therapy at six institutions. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with SUC. We identified 44 and 18 patients with PUC and SUC, respectively. Squamous differentiation was the most common subtype element, followed by glandular differentiation and sarcomatoid subtype. Although patients with SUC had a comparable ORR to those with PUC, the duration of response for SUC was short. Patients with SUC had poorer PFS than those with PUC; however, no significant difference was observed in OS. Multivariate analysis revealed that SUC was significantly associated with shorter PFS. Although the response of metastatic SUC to EV was similar to that of PUC, SUC showed faster progression than PUC. [ABSTRACT FROM AUTHOR]

Background: To investigate the prognostic significance of systemic inflammation score (SIS) in upper tract urothelial carcinoma (UTUC) in patients undergoing radical nephroureterectomy (RNU). Methods: A total of 313 UTUC patients who underwent RNU at West China Hospital from May 2014 to June 2019 were retrospectively analyzed. The predictive value of SIS for relevant endpoints, including overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS), was assessed by Kaplan–Meier curves and the Cox proportional hazards model. Results: According to inclusion and exclusion criteria, 218 UTUC patients were ultimately included in this cohort study. Statistical analysis shows that increased SIS was significantly associated with higher TNM stage (p = 0.017), lower BMI (p = 0.037), absence of hemoglobin (p < 0.001), and pathologic necrosis (p = 0.007). Kaplan–Meier survival curves clearly visually stratified survival for the three outcomes. After adjusting for tumor grade, the multivariate Cox proportional hazards model results showed that SIS was an independent risk factor for poor OS and CSS (HR = 1.89, 95% CI: 1.11–3.21, p = 0.0183, HR = 1.89, 95% CI: 1.07–3.33, p = 0.0285) in the advanced group. Conclusions: SIS was an independent risk factor for OS and CSS after RNU in patients with high-grade UTUC. It may be a novel and conducive tool for preoperative risk stratification and guiding individualized therapy for high-risk UTUC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Upper tract urinary carcinoma (UTUC) is a rare type of cancer affecting the urinary system. Patients with UTUC often undergo surgeries like kidney-sparing surgery or radical nephroureterectomy. However, even after treatment, there remains a risk of the cancer recurring in different parts of the body. This narrative review aims to better understand the frequency and locations of such recurrences, which is crucial for effectively monitoring patients after their initial treatment. Currently, there is limited information on the optimal methods for tracking patients post-surgery, and on how early detection of cancer, before the appearance of symptoms, might improve health outcomes. This article presents the most important current guideline recommendations and elucidates the evidence behind them. Exploring new imaging technologies and improving methods for assessing patient risk, can potentially lead to more personalized and effective monitoring plans in the near future. 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. [ABSTRACT FROM AUTHOR]

Metastatic upper tract urothelial carcinoma (mUTUC) has a poor prognosis. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in patients with metastatic urothelial carcinoma. However, data supporting the use of ICIs in patients with mUTUC are limited. A promising synergy between ICI and concomitant radiotherapy (RT) has been reported in patients with mUTUC. Our research involved a case-based investigation and emphasized the successful integration of different specialists' skills. Observed after partial urethrectomy procedures for muscle-invasive upper tract urothelial carcinoma (UTUC), the radiological detection of lung metastases prompted us to implement cisplatin-based first-line chemotherapy and molecular characterization in the treatment process. We uncovered alterations in the ERBB2 and FGFR3 genes and mismatch repair deficiency at a molecular level. First-line chemotherapy treatment led to a stable disease, and the patient was started on maintenance immunotherapy with Avelumab. Subsequently, an increase in the size of the lung nodules was described, and the patient received radiotherapy for three lung lesions in combination with immunotherapy. After 3 months, a restaging CT scan reported a complete response, which is still ongoing. We discuss the mechanisms driving RT/ICI synergy and the molecular profile of mUTUC as factors that should be considered in therapeutic strategy planning. Molecular insight enhances the originality of our study, providing a nuanced understanding of the genetic landscape of mUTUC and paving the way for targeted therapeutic strategies. The therapeutic armamentarium expansion encourages the design of a multimodal and personalized approach for each mUTUC patient, taking into account tumor heterogeneity and molecular profiling. [ABSTRACT FROM AUTHOR]

Simple Summary: Radical prostatectomy (RP) is a common treatment for prostate cancer but has a risk of side-effects. Urinary incontinence (UI) after RP ranges from 4 to 31%, depending on the method of reporting and definitions used. The aim of this study was to evaluate if healthcare insurance claims data of absorbing pads in the Netherlands provide a valid alternative in the measurement of post-prostatectomy UI (defined as the use of ≥1 pad(s) per day), compared to self-reported pad use. Claims data and self-reported use was available for 416 patients. According to the claims data, patients had a UI rate of 31%, compared to a self-reported UI rate of 45% one year after RP. The agreement between both measures was moderate. Claims data can be considered as a conservative quality indicator for UI after RP. The use of healthcare insurance claims data for urinary incontinence (UI) pads has the potential to serve as an objective measure for assessing post-radical prostatectomy UI rates, but its validity for this purpose has not been established. The aim of this study is to correlate claims data with Patient Reported Outcome Measures (PROMs) for UI pad use. Patients who underwent RP in the Netherlands between September 2019 and February 2020 were included. Incontinence was defined as the daily use of ≥1 pad(s). Claims data for UI pads at 12–15 months after RP were extracted from a nationwide healthcare insurance database in the Netherlands. Participating hospitals provided PROMS data. In total, 1624 patients underwent RP. Corresponding data of 845 patients was provided by nine participating hospitals, of which 416 patients were matched with complete PROMs data. Claims data and PROMs showed 31% and 45% post-RP UI (≥1 pads). UI according to claims data compared with PROMs had a sensitivity of 62%, specificity of 96%, PPV of 92%, NPV of 75% and accuracy of 81%. The agreement between both methods was moderate (κ = 0.60). Claims data for pads moderately align with PROMs in assessing post-prostatectomy urinary incontinence and could be considered as a conservative quality indicator. [ABSTRACT FROM AUTHOR]

Simple Summary: This review examines differences and similarities between upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) with respect to their epidemiological, clinical, pathological, and biological features and discusses the resulting therapeutic consequences. Systemic treatments for invasive and metastatic diseases are considered, and an overview of the expected developments in this field is provided. Upper tract urothelial carcinoma (UTUC) is a rare disease included, along with the much more frequent urothelial bladder cancer (BUC), in the family of urothelial carcinomas (UCs). However, while UTUCs and BUCs share several features, their epidemiological, clinical, pathological, and biological differences must be considered to establish an optimal therapeutic strategy. This review examines the clinical differences between UTUC and BUC, as well as the main results obtained by molecular screening of the two diseases. The findings of clinical trials, performed in peri-operative and metastatic settings and assessing systemic treatments in UC, are summarised. A comparison of the data obtained for UTUC and BUC suggests improved therapeutic approaches, both in regards to routine practice and future drug development. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for the treatment of metastatic urothelial carcinoma (mUC). Methods: A literature search was conducted of PubMed, EMBASE, and the Cochrane Library and was limited to the English literature. Randomized controlled trials (RCTs) published up to July 2022 were considered for inclusion. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade ≥ 3 treatment-related AEs (TRAE). Subgroup analysis was performed based on the PD-L1 expression status, and the differences between first- and second-line PD-1/PD-L1 inhibitors were estimated. Results: We included five RCTs comprising 3584 patients in the analysis. Compared with chemotherapy alone, the use of PD-1/PD-L1 inhibitors as monotherapy did not significantly prolong OS [hazard ratios (HR), 0.90; 95% CI, 0.81–1.00] or PFS (HR, 1.12; 95% CI, 0.95–1.32). However, the PD-1/PD-L1 inhibitor combined with chemotherapy significantly improved both OS (HR, 0.85; 95% CI, 0.74–0.96) and PFS (HR, 0.80; 95% CI, 0.71–0.90). Additionally, subgroup analysis showed that in mUC with PD-L1 expression ≥ 5%, treatment with the PD-1/PD-L1 inhibitor alone did not reduce the risk of death. Safety analysis showed that the PD-1/PD-L1 inhibitor alone did not significantly increase the incidence rates of grade ≥ 3 TRAEs. Conclusions: The results show that use of the PD-1/PD-L1 inhibitor alone as first-line treatment is similar to chemotherapy in terms of both survival and response rates. However, the PD-1/PD-L1 inhibitor plus chemotherapy has a significant benefit in terms of PFS or OS. Nonetheless, more RCTs are warranted to evaluate efficiency and safety in the combination regimen of chemotherapy and PD-1/PD-L1 inhibitors. [ABSTRACT FROM AUTHOR]

Radical cystectomy (RC) is an integral part of the management of patients with advanced-stage bladder cancer. This major oncologic operation is prone to complications resulting in morbidity and mortality. We analyzed the critical steps of open RC, performed an evidence-based review of these steps, and discussed our experience and approach. We conducted a literature review of the open RC technique, identified the critical steps that consistently appeared across different sources, and organized these steps into a framework. PubMed was queried with the critical steps as keywords for relevant articles published from 1 January 2013 to 1 August 2023. We utilized this query to conduct a systematic review of the literature using the outcomes of overall survival and 90-day complication rate. We developed the "Summary for the 10 Critical Operative Steps of Radical Cystectomy", a concise guide to the approach to open RC. When available, an evidence-based analysis of each critical step was performed. We also included additional components of cystectomy optimization such as pre-habilitation in the preoperative phase, standard versus extended lymphadenectomy, the vaginal-sparing approach to female radical cystectomy, patient-reported outcomes following urinary diversion, the use of a mesh for stoma formation, and the use of the ERAS protocol for postoperative care. An evidence-based assessment of RC may help provide valuable information to optimize surgical techniques and patient outcomes. [ABSTRACT FROM AUTHOR]

The 2019 coronavirus disease (COVID-19) pandemic has had a profound influence on different sectors of society, including health. This study hypothesized a significant impact of the pandemic on the quality of life and psychosocial well-being of urothelial cancer patients, specifically anticipating a decrease in anxiety and depression scores as the pandemic progressed. The primary objectives were to assess longitudinal changes in quality of life indexes, evaluate Healthcare Anxiety and Depression Scale (HADS) score trends over three years (2020–2022), and identify any correlational patterns between the progression of the pandemic and anxiety, depression, and stress levels among this cohort. A cross-sectional analysis was conducted on Eastern Cooperative Oncology Group (ECOG) 1 and Tumor Node Metastasis (TNM) stage 1 bladder cancer patients from the Timis County Emergency Clinical Hospital in Romania. Sixty patients were evaluated each year from 2020 to 2022, utilizing a detailed selection process involving the review of both the hospital database and paper records. Key data included demographic information, medical history, and responses to the Patient Health Questionnaire (PHQ-9), Short Form (SF-36), HADS, and Generalized Anxiety Disorder (GAD-7) questionnaires. A total of 163 completed questionnaires were analyzed, providing insight into various aspects of patients' experiences during the pandemic. Notably, the mean hospitalization days ranged from 3.6 ± 2.1 days in 2020 to 4.0 ± 2.4 days in 2022 (p = 0.663). Concerns that current symptoms might be pandemic-related spiked to 63.5% in 2021, but reduced to 50.9% in 2022, with this fluctuation being significant (p = 0.026). The perception of decreased quality of or accessibility to medical care was significant over the years, with a decline to 52.7% in 2022 (p = 0.033). Quality of life assessments demonstrated an upward trend, from an average score of 55.9 ± 8.9 in 2020 to 59.3 ± 8.8 in 2022 (p = 0.049). Interestingly, anxiety levels, as indicated by the HADS survey, revealed a significant decline from a score of 7.8 in 2020 to 6.5 in 2022 (p = 0.008). On the other hand, GAD-7 scores displayed a downward trend over the years, potentially indicative of developed coping strategies (p = 0.034). This study provides a comprehensive insight into the fluctuating dynamics of psychosocial factors and quality of life among urothelial cancer patients during the pandemic years. It underscores a potential adaptive response, as evidenced by the decrease in anxiety levels and an upward trend in the quality of life scores over the period. These findings highlight the resilience and adaptability of this patient cohort amidst the challenges posed by the pandemic, potentially guiding future interventions and supports in similar health crises. [ABSTRACT FROM AUTHOR]

Simple Summary: Upper tract urothelial cancer is an aggressive malignancy that requires prompt treatment in the form of removal of the kidney and ureter with a bladder cuff, especially for invasive disease. The ideal surgical technique should offer a complete cancer clearance, including the ability to remove lymph glands with a short recovery period. The three techniques currently available include open, laparoscopic, and robotic approaches. This review compares the three techniques both on cancer clearance and survival by analyzing the existing literature. We found the robotic technique to be similar or slightly superior to either the open or laparoscopic approach for overall survival, cancer-specific survival, lymph node removal rates, and the rates of risk for residual cancer (positive margins). However, the risk of recurrent tumours in the bladder was identified to be higher in robotic surgery compared to the open approach. The study determines that the robotic approach offers comparable outcomes to the open and laparoscopic approaches, which are well established but for which the overall quality of evidence has been poor. Introduction and Aims: The optimal approach for nephroureterectomy in patients with suspected UTUC remains a point of debate. In this review, we compare the oncological outcomes of robotic nephroureterectomy (RNU) with open (ONU) or laparoscopic nephroureterectomy (LNU). Methods: All randomized trials and observational studies comparing RNU with ONU and/or LNU for suspected non-metastatic UTUC are included in this review. The systematic review was performed in accordance with the Cochrane Guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The primary outcome measures were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IV-RFS). The secondary outcome measures were the lymph node dissection (LND) rates, positive margin rates, and the proportion of patients receiving bladder intravesical chemotherapy. Results: We identified 8172 references through our electronic searches and 8 studies through manual searching. A total of 15 studies met the inclusion criteria. The total number of patients in the review was 18,964. RNU had superior OS compared to LNU (HR: 0.81 (95% CI: 0.71, 0.93), p-0.002 (very low certainty)). RNU and ONU had similar OS (HR: 0.83 (95% CI: 0.52, 1.34), p-0.44 (very low certainty)). One study reported an independent association of RNU as a worse predictor of IV-RFS when compared to ONU (HR-1.73 (95% CI: 1.22, 2.45)). The LND rates were higher in the RNU cohort when compared to the LNU cohort (RR 1.24 (95% CI: 1.03, 1.51), p-0.03 (low certainty)). The positive margin rate was lower in the RNU cohort when compared to the ONU cohort (RR 0.29 (95% CI: 0.08, 0.86), p-0.03 (low certainty)). Conclusion: RNU offers comparable oncological efficacy to ONU, except for intravesical recurrence-free survival (IV-RFS). RNU has fewer positive surgical margin rates compared to ONU in well-balanced studies. RNU appears to outperform LNU for certain oncological parameters, such as OS and the proportion of patients who receive lymph node dissections. The quality of evidence comparing surgical techniques for UTUC has remained poor in the last decade. [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding how effective a treatment is before a major bladder surgery can help doctors to plan better patient care. Our research investigated the survival rates of patients who received neoadjuvant chemotherapy before having their bladders removed due to cancer. We wanted to examine if there were differences in survival for those who had certain signs of cancer in their lymph nodes after the chemotherapy. Our findings suggest that those who showed these signs and had received prior chemotherapy had a more challenging health outlook than those who directly went for surgery. This information is crucial as it may guide doctors to consider additional treatments and closer patient monitoring in certain cases. Our study helps to provide a clearer picture for both doctors and patients when making decisions about bladder cancer treatment. Patients receiving neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) typically show better survival outcomes than those undergoing immediate surgery for muscle-invasive bladder cancer. However, most studies have not considered the lymph node (LN) status when evaluating NAC's survival benefits. This study sought to delineate the impact of NAC on patients based on their pathologically determined LN status at the time of RC. We examined data from 1395 patients treated at two departments between 1991 and 2022. Of them, 481 had positive LNs. A comparison of overall survival (OS) outcomes revealed that patients without LN involvement ((y)pN0) benefited from NAC with a hazard ratio (HR) of 0.692 (95% confidence interval [CI] 0.524–0.915). In contrast, patients with (y)pN+ showed no improvement with NAC (HR 0.927, 95%CI 0.713–1.205). Notably, patients treated with NAC for stage

Simple Summary: As upper tract urothelial carcinoma is a relatively rare disease, much of clinical practice has been extrapolated from urothelial carcinoma data. Here we summarize data, current guidelines, and future directions in the management of upper tract urothelial carcinoma with a particular focus on systemic therapy. Upper tract urothelial carcinoma comprises 5–10% of all urothelial carcinoma cases. This disease tends to have a more aggressive course than its lower urinary tract counterpart, with 60% of patients presenting with invasive disease and 30% of patients presenting with metastatic disease at diagnosis. The diagnostic workup of UTUC involves imaging with CT urogram, urine cytology, and direct visualization and biopsy of suspected lesions via ureteroscopy. Standard treatment of high-grade UTUC involves radical nephroureterectomy (RNU) and excision of the ipsilateral bladder cuff. Both the NCCN and EAU Guidelines include neoadjuvant chemotherapy as a treatment option for select patients with UTUC; however, there are no strict guidelines. Much of the rationale for neoadjuvant chemotherapy is based on extrapolation from data from muscle-invasive bladder cancer, which has demonstrated a 5-year OS benefit of 5–8%. Retrospective studies evaluating the use of NACT in urothelial carcinoma have yielded pathologic objective response rates of 48% in UTUC cohorts. The randomized Phase III POUT study noted a DFS advantage with adjuvant platinum-based chemotherapy, compared with surveillance in UTUC, of 70% vs. 51% at 2 years. Though not the standard of care, multiple studies have explored the use of perioperative immunotherapy or chemoimmunotherapy in the management of invasive urothelial carcinoma. The PURE-02 study explored the use of neoadjuvant pembrolizumab in patients with high-risk UTUC. A small study of 10 patients, it showed no significant signals of activity with neoadjuvant pembrolizumab. Another Phase II study of neoadjuvant ipilimumab and nivolumab in cisplatin-ineligible UTUC yielded more promising findings, with 3/9 patients attaining a pathologic CR and the remaining six pathologically downstaged. The ABACUS trial found a 31% pathologic complete response rate amongst cisplatin-ineligible MIBC patients treated with neoadjuvant atezolizumab. The use of adjuvant immunotherapy has been explored over three phase III trials. The CheckMate-274 trial found a DFS benefit with the addition of one year of adjuvant nivolumab in patients with high-risk urothelial carcinoma. The IMvigor-010 study of adjuvant atezolizumab was a negative study. The AMBASSADOR trial of adjuvant pembrolizumab is pending results. With the FDA approval of erdafitinib in metastatic urothelial carcinoma, similar targets have been explored for use in perioperative use in invasive urothelial carcinoma, as with adjuvant infigratinib in the PROOF-302 trial. As the treatment paradigm for urothelial carcinoma evolves, further prospective studies are needed to expand the perioperative treatment landscape of UTUC. [ABSTRACT FROM AUTHOR]

Urinary tract cancers are considered life-threatening conditions worldwide, and Bladder Cancer is one of the most malignant urinary tract tumors, with an estimated number of more than 1.3 million cases worldwide each year. Bladder Cancer is a heterogeneous disease; the main symptom is painless hematuria. However, patients with Bladder Cancer may initially be misdiagnosed as Cystitis or infection, and cystoscopy alone may sometimes be misdiagnosed as urolithiasis or Cystitis, thereby delaying medical attention. Early diagnosis of Bladder Cancer is the key to successful treatment. This study uses six deep learning methods through different oversampling techniques and feature selection, and then through dimensionality reduction techniques, to establish a set that can effectively distinguish between Bladder Cancer and Cystitis patient's deep learning model. The research results show that based on the laboratory clinical dataset, the deep learning model proposed in this study has an accuracy rate of 89.03% in distinguishing between Bladder Cancer and Cystitis, surpassing the results of previous studies. The research model developed in this study can be provided to clinicians as a reference to differentiate between Bladder Cancer and Cystitis. [ABSTRACT FROM AUTHOR]

Despite the arising interest in three-dimensional (3D) reconstruction models from 2D imaging, their diffusion and perception among urologists have been scarcely explored. The aim of the study is to report the results of an international survey investigating the use of such tools among urologists of different backgrounds and origins. Beyond demographics, the survey explored the degree to which 3D models are perceived to improve surgical outcomes, the procedures mostly making use of them, the settings in which those tools are mostly applied, the surgical steps benefiting from 3D reconstructions and future perspectives of improvement. One hundred responders fully completed the survey. All levels of expertise were allowed; more than half (53%) were first surgeons, and 59% had already completed their training. Their main application was partial nephrectomy (85%), followed by radical nephrectomy and radical prostatectomy. Three-dimensional models are mostly used for preoperative planning (75%), intraoperative consultation and tailoring. More than half recognized that 3D models may highly improve surgical outcomes. Despite their recognized usefulness, 77% of responders use 3D models in less than 25% of their major operations due to costs or the extra time taken to perform the reconstruction. Technical improvements and a higher availability of the 3D models will further increase their role in surgical and clinical daily practice. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnosis and prediction of prognosis for bladder cancer (BC) can be challenging because of the subjective nature of pathological evaluation. Artificial intelligence (AI) has emerged as a promising technology for improving the accuracy of BC diagnosis and prediction of prognosis. We reviewed all available studies that used AI to analyze images from BC tumor tissue that aimed to improve diagnosis or prediction of prognosis. Studies showed that specific tumor characteristics can be used to predict treatment response by analyzing BC tumor tissue images. Combining histopathological images with clinical information enables AI models to perform with high accuracy. In conclusion, AI has the potential to assist physicians in gaining more accurate diagnoses and treatment response predictions. Yet, important challenges should be addressed, such as ensuring reliability, interpretability, and performance—future research should address these caveats. Bladder cancer (BC) diagnosis and prediction of prognosis are hindered by subjective pathological evaluation, which may cause misdiagnosis and under-/over-treatment. Computational pathology (CPATH) can identify clinical outcome predictors, offering an objective approach to improve prognosis. However, a systematic review of CPATH in BC literature is lacking. Therefore, we present a comprehensive overview of studies that used CPATH in BC, analyzing 33 out of 2285 identified studies. Most studies analyzed regions of interest to distinguish normal versus tumor tissue and identify tumor grade/stage and tissue types (e.g., urothelium, stroma, and muscle). The cell's nuclear area, shape irregularity, and roundness were the most promising markers to predict recurrence and survival based on selected regions of interest, with >80% accuracy. CPATH identified molecular subtypes by detecting features, e.g., papillary structures, hyperchromatic, and pleomorphic nuclei. Combining clinicopathological and image-derived features improved recurrence and survival prediction. However, due to the lack of outcome interpretability and independent test datasets, robustness and clinical applicability could not be ensured. The current literature demonstrates that CPATH holds the potential to improve BC diagnosis and prediction of prognosis. However, more robust, interpretable, accurate models and larger datasets—representative of clinical scenarios—are needed to address artificial intelligence's reliability, robustness, and black box challenge. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer originating from renal tubular epithelial cells, with clear cell RCC comprising approximately 80% of cases. The primary treatment modalities for RCC are surgery and targeted therapy, albeit with suboptimal efficacies. Despite progress in RCC research, significant challenges persist, including advanced distant metastasis, delayed diagnosis, and drug resistance. Growing evidence suggests that extracellular vesicles (EVs) play a pivotal role in multiple aspects of RCC, including tumorigenesis, metastasis, immune evasion, and drug response. These membrane-bound vesicles are released into the extracellular environment by nearly all cell types and are capable of transferring various bioactive molecules, including RNA, DNA, proteins, and lipids, aiding intercellular communication. The molecular cargo carried by EVs renders them an attractive resource for biomarker identification, while their multifarious role in the RCC offers opportunities for diagnosis and targeted interventions, including EV-based therapies. As the most versatile type of EVs, exosomes have attracted much attention as nanocarriers of biologicals, with multi-range signaling effects. Despite the growing interest in exosomes, there is currently no widely accepted consensus on their subtypes and properties. The emerging heterogeneity of exosomes presents both methodological challenges and exciting opportunities for diagnostic and clinical interventions. This article reviews the characteristics and functions of exosomes, with a particular reference to the recent advances in their application to the diagnosis and treatment of RCC. [ABSTRACT FROM AUTHOR]

Over the last years, prostate magnetic resonance imaging (MRI) has gained a key role in the primary diagnosis of clinically significant prostate cancer (csPCa). While a negative MRI can avoid unnecessary prostate biopsies and the overdiagnosis of indolent cancers, a positive examination triggers biopsy samples targeted to suspicious imaging findings, thus increasing the diagnosis of csPCa with a sensitivity and negative predictive value of around 90%. The limitations of MRI, including suboptimal positive predictive values, are fueling debate on how to stratify biopsy decisions and management based on patient risk and how to correctly estimate it with clinical and/or imaging findings. In this setting, "next-generation imaging" imaging based on radiolabeled Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is expanding its indications both in the setting of primary staging (intermediate-to-high risk patients) and primary diagnosis (e.g., increasing the sensitivity of MRI or acting as a problem-solving tool for indeterminate MRI cases). This review summarizes the current main evidence on the role of prostate MRI and PSMA-PET as tools for the primary diagnosis of csPCa, and the different possible interaction pathways in this setting. [ABSTRACT FROM AUTHOR]

Simple Summary: In the last years, metastasis-directed treatments of oligometastatic renal cell carcinoma (RCC) have been widely investigated. Metachronous solitary or oligometastasis from RCC are considered the ideal candidates for target treatments, allowing the achievement of "non-evidence of disease" status. To date, there have been no randomized clinical trials demonstrating the absolute survival benefits of surgical metastasectomy (MST) for oligo progression of RCC compared to systemic treatments. The role of complete MST on oncological outcomes, at the time of local or distant disease recurrence, remains poorly addressed. This is the first study presenting the advantage of minimally invasive MST on long-term (ten years) overall survival probability in patients who experienced oligoprogression of RCC treated at a high-volume center, compared to cases who received ST only. Objectives: The role of surgical metastasectomy (MST) in solitary or oligometastasis from renal cell carcinoma (RCC) and its impact on survival outcomes remains poorly addressed. We evaluated the impact of MST on overall survival (OS) in patients with oligometastatic (m)RCC. Materials and methods: The institutional renal cancer prospective database was examined for cases treated with partial or radical nephrectomy who developed metastatic disease during follow-up. Patients with evidence of clinical metastasis at first diagnosis were excluded. Patients considered unfit for MST received systemic treatment (ST); all others received MST. The impact of MST vs. the ST only cohort was assessed with the Kaplan–Meier method. Age, gender, bilaterality, histology, AJCC stage of primary tumor, surgical margins, local vs. distant metastasis and MST were included in univariable and multivariable regression analyses to assess the predictors of OS. Results: Overall, at a median follow-up of 16 months after primary treatment, 168 patients with RCC developed asynchronous metastasis at the adrenal gland, lung, liver, spleen, peritoneal, renal fossa, bone, nodes, brain and thyroid gland. Nine patients unfit for any treatment were excluded. The site of metastasis was treated with surgical MST (77/159, 48.4%), with or without previous or subsequent ST, while 82/159 cases (51.2%) received ST only. The 2-year, 5-year and 10-year OS probabilities were 93.8%, 82.8% and 79.5%, respectively. After multivariable analysis, MST and the primary tumor AJCC stage were independent predictors of OS probabilities (p = 0.019 and p = 0.035, respectively). After Kaplan–Meier analysis, MST significantly improved OS probabilities versus patients receiving ST (p < 0.001). Limitations: The main drawbacks of our research were the small sample size from a single-tertiary referral institution, as well as the absent or different ST lines in the cohort of patients receiving MST. Conclusions: When an NED status is achievable, surgical MST of mRCC significantly impacts OS, delaying and not precluding further subsequent ST. [ABSTRACT FROM AUTHOR]

Upper tract urothelial carcinoma (UTUC) is a rare malignancy, occurring in 5–10% of patients diagnosed with UC, and involves the renal pelvis, calyces, or ureters. UTUC can be sporadic or hereditary as a clinical manifestation of Lynch syndrome. Therapeutic management of these patients is challenging. Following risk stratification of localized disease, patients with low-grade UTUC may undergo kidney-sparing surgery or radical nephroureterectomy (RNU) and/or chemoablation with mitomycin-c instillation to reduce recurrence. In high-grade disease, RNU followed by adjuvant chemotherapy remains the standard of care. For decades, platinum-based chemotherapy has been the cornerstone of treatment for locally advanced and metastatic disease. The aim of the present review is to summarize recent advances in UTUC's therapeutic management through the lens of its genomic and immune landscape. Accumulating knowledge on the genetic and immune aspects of UTUC tumors has increased our understanding of their underlying biology, supporting a luminal papillary, T-cell depleted contexture and enrichment in fibroblast growth factor receptor (FGFR) expression. These advances have fueled successful clinical testing of several precision-based therapeutic approaches, including immune checkpoint inhibitors (ICIs), the antibody–drug conjugates (ADCs) enfortumab vedotin and sacituzumab govitecan, and agents targeting the FGFR axis such as erdafitinib and other kinase inhibitors, allowing their entry into the therapeutic armamentarium and improving the prognosis of these patients. Not all patients respond to these precision-based targeted therapies; thus, validating and expanding the toolkit of potential biomarkers of response or resistance, including molecular subtypes, FGFR pathway gene alterations, DNA repair gene defects, tumor mutational burden (TMB), circulating tumor DNA (ctDNA), nectin-4, TROP2, and programmed death ligand-1 (PD-L1), are key to maximizing the benefit to these particular subgroups of patients. [ABSTRACT FROM AUTHOR]