PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is a rare malignancy posing significant diagnostic and management challenges. This review provides an overview of the evidence supporting various imaging modalities and offers insights into future innovations in UTUC imaging. RECENT FINDINGS: With the growing use of advancements in computed tomography (CT) technologies for both staging and follow-up of UTUC patients, continuous innovations aim to enhance performance and minimize the risk of excessive exposure to ionizing radiation and iodinated contrast medium. In patients unable to undergo CT, magnetic resonance imaging serves as an alternative imaging modality, though its sensitivity is lower than CT. Positron emission tomography, particularly with innovative radiotracers and theranostics, has the potential to significantly advance precision medicine in UTUC. Endoscopic imaging techniques including advanced modalities seem to be promising in improved visualization and diagnostic accuracy, however, evidence remains scarce. Radiomics and radiogenomics present emerging tools for noninvasive tumor characterization and prognosis. SUMMARY: The landscape of imaging for UTUC is rapidly evolving, with significant advancements across various modalities promising improved diagnostic accuracy, patient outcomes, and safety.

• MeSH
• Carcinoma, Transitional Cell * diagnosis   diagnostic imaging   therapy   pathology   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Kidney Neoplasms diagnostic imaging   therapy   diagnosis   pathology   MeSH
• Ureteral Neoplasms diagnostic imaging   diagnosis   therapy   pathology   MeSH
• Tomography, X-Ray Computed methods   MeSH
• Positron-Emission Tomography methods   MeSH
• Neoplasm Staging MeSH
• Urologic Neoplasms diagnosis   diagnostic imaging   therapy   pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Uroteliální karcinom (UC) představuje závažný onkologický problém s vysokou mortalitou, zejména u pokročilých stadií. Adjuvantní terapie, ať už chemoterapie, nebo imunoterapie, hraje klíčovou roli ve snižování rizika relapsu a zlepšení přežití po radikální operaci. Tento přehled shrnuje současné poznatky o využití adjuvantní léčby u UC a uroteliálního karcinomu horních cest močových (UTUC), včetně jeho histologických variant. Nejlépe etablovanou modalitou je chemoterapie na bázi cisplatiny, která prokázala přínos zejména u pacientů s vysokým rizikem relapsu (pT3-4, N+) bez předchozí neoadjuvantní chemoterapie. Významný průlom přinesla imunoterapie, zejména nivolumab, jehož účinnost byla potvrzena v randomizované studii CheckMate 274, přičemž největší benefit byl pozorován u pacientů s vysokou expresí PD-L1. Problematické zůstává postavení adjuvantní terapie u histologických variant UC, kde je potřeba dalšího výzkumu. Budoucí směřování adjuvantní léčby zahrnuje identifikaci prediktivních biomarkerů, včetně ctDNA, a vývoj personalizovaných strategií, které zohlední molekulární a imunitní charakteristiky nádoru. Optimalizace selekce pacientů pomocí tekutých biopsií a dalších biomarkerů je klíčem ke zlepšení dlouhodobých výsledků.

Urothelial carcinoma (UC) represents a significant oncological challenge with high mortality, particularly in advanced stages. Adjuvant therapy, whether chemotherapy or immunotherapy, plays a crucial role in reducing the risk of relapse and improving survival after radical surgery. This review summarises current knowledge on the use of adjuvant treatment in UC and upper tract urothelial carcinoma (UTUC), including its histological variants. The most established modality remains cisplatin-based chemotherapy, which has demonstrated benefits, particularly in patients at high risk of relapse (pT3-4, N+) without prior neoadjuvant chemotherapy. A major breakthrough has been the introduction of immunotherapy, especially nivolumab, whose efficacy was confirmed in the randomised CheckMate 274 trial, with the most significant be­nefit observed in patients with high PD-L1 expression. The role of adjuvant therapy in histological variants of UC remains unclear and requires further research. The future direction of adjuvant treatment involves the identification of predictive biomarkers, including circulating tumour DNA (ctDNA) and developing personalised strategies that consider the molecular and immune characteristics of the tumour. Optimising patient selection using liquid biopsies and other biomarkers is key to improving long-term outcomes.

• MeSH
• Chemotherapy, Adjuvant MeSH
• Immunotherapy methods   MeSH
• Carcinoma, Transitional Cell * drug therapy   MeSH
• Humans MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Randomized Controlled Trials as Topic MeSH
• Urologic Neoplasms drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

BACKGROUND AND OBJECTIVE: We present a summary of the 2025 update for the European Association of Urology (EAU) guidelines for upper urinary tract urothelial carcinoma (UTUC). The aim is to provide practical recommendations on the clinical management of UTUC with a focus on diagnosis, treatment, and follow-up. METHODS: For the 2025 guidelines on UTUC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with UTUC. The guidelines stress the importance of appropriate treatment taking into account patient values and preferences. Key updates in the 2025 UTUC guidelines include: significant changes to the recommendations for UTUC diagnosis; complete revision of the sections addressing risk stratification, ureteroscopy, and the surgical approach for radical nephroureterectomy; addition of four new recommendations, two related to kidney-sparing management of localised low-risk UTUC and a further two related to management of high-risk nonmetastatic UTUC; a review and adaptation of recommendation for UTUC follow-up; and addition of a new section addressing quality indicators for UTUC management. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2025 EAU guidelines on UTUC offers valuable insights into risk factors, diagnosis, classification, treatment, and follow-up for UTUC. The guidelines contain information on the management of individual patients according to the current best evidence and are designed for effective integration in clinical practice.

• MeSH
• Carcinoma, Transitional Cell * therapy   diagnosis   MeSH
• Humans MeSH
• Kidney Neoplasms * therapy   diagnosis   MeSH
• Ureteral Neoplasms * therapy   diagnosis   MeSH
• Societies, Medical MeSH
• Urology standards   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH

BACKGROUND AND OBJECTIVE: Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate. KEY FINDINGS AND LIMITATIONS: Overall, 15 studies evaluated the effectiveness of adding chemotherapy to RNU in the perioperative setting without specifying the exact timing of delivery (n = 1), in the induction setting (n = 14), or in the adjuvant setting (n = 5), while two studies evaluated the effectiveness of adding RNU to chemotherapy. Meta-analyses showed that the use of induction chemotherapy plus RNU versus RNU alone was associated with greater odds of pathological downstaging (risk ratio [RR] = 3.06; 95% confidence interval [CI] = [2.48-3.77]; p < 0.001; I2 = 0%; p = 0.44) and pathological complete nodal response (RR = 2.80; 95% CI = [2.03-3.86]; p < 0.001; I2 = 0%; p = 0.47) as well as prolonged overall survival (HR = 0.52; 95% CI = [0.42-0.64]; p < 0.001; I2 = 14%; p = 0.33) without any significant impact on the risk of overall (RR = 1.14; 95% CI = [0.79-1.64]; p = 0.48; I2 = 0%; p = 0.76) and major (RR = 0.48; 95% CI = [0.18-1.24]; p = 0.13; I2 = 0%; p = 0.87) postoperative complications. In addition, the use of induction chemotherapy plus RNU versus RNU plus adjuvant chemotherapy (HR = 0.58; 95% CI = [0.38-0.89]; p = 0.01) or chemotherapy alone (HR = 0.49; 95% CI = [0.32-0.76]; p = 0.001; I2 = 46%; p = 0.17) was associated with prolonged overall survival. Limitations include the observational design of all included studies. CONCLUSIONS AND CLINICAL IMPLICATIONS: The use of RNU could provide the greatest oncological benefits without any significant harm in selected UTUC patients with fit general condition and resectable cN+ disease responding to induction chemotherapy. PATIENT SUMMARY: In this report, we looked at the outcomes of radical surgery in combination with systemic chemotherapy for upper tract urothelial carcinoma with clinical evidence of dissemination to the surrounding lymph nodes. We observed that the use of radical surgery was associated with the greatest oncological benefits without any increased risk of postoperative complications in patients with fit general condition and resectable disease responding to induction chemotherapy. We conclude that the use of induction chemotherapy plus radical surgery could be the best multimodal treatment strategy for these patients.

• MeSH
• Carcinoma, Transitional Cell * pathology   surgery   therapy   MeSH
• Combined Modality Therapy MeSH
• Humans MeSH
• Lymphatic Metastasis MeSH
• Kidney Neoplasms * pathology   surgery   therapy   MeSH
• Ureteral Neoplasms * pathology   surgery   therapy   MeSH
• Nephroureterectomy * methods   adverse effects   MeSH
• Practice Guidelines as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review 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.

• Publication type
• Journal Article MeSH
• Case Reports MeSH

BACKGROUND: High-level evidence supporting the role of repeat transurethral resection (reTUR) in non-muscle-invasive bladder cancer (NMIBC) is lacking. A randomized controlled trial (RCT) assessing whether immediate reTUR has an impact on patient prognosis is essential. However, since such a RCT will require enrollment of a high number of patients, a preliminary feasibility study is appropriate. OBJECTIVE: To assess the feasibility of an RCT investigating the impact of immediate reTUR + adjuvant bacillus Calmette-Guérin (BCG) versus upfront induction BCG after initial TUR in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Eligible patients were randomly assigned to receive either reTUR + adjuvant BCG or upfront induction BCG after TUR. Patients with macroscopically completely resected high-grade T1 NMIBC, with or without concomitant carcinoma in situ, and with detrusor muscle (DM) present in the initial TUR specimen were considered eligible for inclusion. Exclusion criteria included lymphovascular invasion (LVI), histological subtypes, hydronephrosis, concomitant upper tract urothelial carcinoma (UTUC), or urothelial carcinoma within the prostatic urethra. The aim was to enroll 30 patients in this feasibility study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The patient recruitment rate was the primary outcome. Oncological outcomes (recurrence-free and progression-free survival) were secondary endpoints. RESULTS AND LIMITATIONS: Overall, 30 patients (15 per arm) were randomized over a period of 14 mo (August 2020-October 2021). Two eligible patients refused the randomization, resulting in a patient compliance rate of 93.3% for the study protocol. We excluded 49 ineligible patients before randomization because of histological subtypes (n = 16, 33%), LVI (n = 9, 18%), DM absence in the TUR specimen (n = 12, 24%), metastatic disease (n = 5, 10%), concomitant UTUC (n = 3, 6%), or hydronephrosis (n = 4, 8%). At reTUR, persistent disease was found in four patients (29%) and upstaging to muscle-invasive disease in one (7%). Over median follow-up of 17 mo, disease recurrence was detected in three patients (23%) in the reTUR arm and six patients (40%) in the upfront BCG arm. Progression to muscle-invasive disease was observed in one patient treated with upfront BCG. CONCLUSIONS: The feasibility of conducting an RCT comparing upfront BCG versus reTUR + BCG in high-grade T1 NMIBC has been demonstrated. Our results underline the need to screen a large number of patients owing to characteristics meeting the exclusion criteria in a high percentage of cases. PATIENT SUMMARY: We found that a clinical trial of the role of a repeat surgical procedure to remove bladder tumors through the urethra would be feasible among patients with high-grade non-muscle-invasive bladder cancer. These preliminary results may help in refining the role of this repeat procedure for patients in this category.

• MeSH
• Adjuvants, Immunologic * therapeutic use   MeSH
• BCG Vaccine * therapeutic use   administration & dosage   MeSH
• Cystectomy methods   MeSH
• Neoplasm Invasiveness * MeSH
• Combined Modality Therapy MeSH
• Middle Aged MeSH
• Humans MeSH
• Non-Muscle Invasive Bladder Neoplasms MeSH
• Urinary Bladder Neoplasms * surgery   pathology   drug therapy   MeSH
• Reoperation MeSH
• Aged MeSH
• Feasibility Studies * MeSH
• Urethra MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

Background: Although previous literature shows tumor location as a prognostic factor in upper tract urothelial carcinoma (UTUC), there remains uninvestigated regarding the impact of tumor location on grade concordance and discrepancies between ureteroscopic (URS) biopsy and final radical nephroureterectomy (RNU) pathology. Methods: In this international study, we retrospectively reviewed the records of 1,498 patients with UTUC who underwent diagnostic URS with concomitant biopsy followed by RNU between 2005 and 2020. Tumor location was divided into four sections: the calyceal-pelvic system, proximal ureter, middle ureter, and distal ureter. Patients with multifocal tumors were excluded from the study. We performed multiple comparison tests and logistic regression analyses. Results: Overall, 1,154 patients were included; 54.4% of those with low-grade URS biopsies were upgraded on RNU. In the multiple comparison tests, middle ureter tumors exhibited the highest probability of upgrading, meanwhile pelvicalyceal tumors exhibited the lowest probability of upgrading (73.7% vs 48.5%, p = 0.007). Downgrading was comparable across all tumor locations. On multivariate analyses, middle ureteral location was significantly associated with a low probability of grade concordance (odds ratio [OR] 0.59; 95% confidence interval [CI], 0.35-1.00; p = 0.049) and an increased risk of upgrading (OR 2.80; 95% CI, 1.20-6.52; p = 0.017). The discordance did not vary regardless of caliceal location, including the lower calyx. Conclusions: Middle ureteral tumors diagnosed to be low grade had a high probability to be undergraded. Our data can inform providers and their patients regarding the likelihood of undergrading according to tumor location, facilitating patient counseling and shared decision making regarding the choice of kidney sparing vs RNU.

• MeSH
• Biopsy MeSH
• Carcinoma, Transitional Cell surgery   pathology   MeSH
• Clinical Relevance MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Neoplasms pathology   surgery   MeSH
• Ureteral Neoplasms * pathology   surgery   MeSH
• Nephroureterectomy methods   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Grading * MeSH
• Ureter pathology   surgery   diagnostic imaging   MeSH
• Ureteroscopy * methods   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

CONTEXT: Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC. OBJECTIVE: To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients. EVIDENCE ACQUISITION: Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU. EVIDENCE SYNTHESIS: Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44-0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06-1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51-0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15-2.34, p = 0.006, respectively). CONCLUSIONS: EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy.

• MeSH
• Carcinoma, Transitional Cell * surgery   pathology   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * epidemiology   MeSH
• Kidney Neoplasms * surgery   pathology   MeSH
• Urinary Bladder Neoplasms * surgery   pathology   MeSH
• Ureteral Neoplasms * surgery   MeSH
• Nephroureterectomy * methods   MeSH
• Ureter surgery   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

Upper tract urothelial carcinoma (UTUC) accounts for the 5-10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6-12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9-6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status.

• MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   MeSH
• Carcinoma, Transitional Cell * drug therapy   pathology   mortality   secondary   MeSH
• Middle Aged MeSH
• Humans MeSH
• Antineoplastic Agents, Immunological therapeutic use   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Urologic Neoplasms drug therapy   pathology   mortality   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.

• MeSH
• Risk Assessment methods   MeSH
• Insulin-Like Growth Factor Binding Protein 3 blood   MeSH
• Insulin-Like Growth Factor I * metabolism   MeSH
• Carcinoma, Transitional Cell surgery   blood   pathology   mortality   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor blood   MeSH
• Nephroureterectomy * methods   MeSH
• Insulin-Like Peptides MeSH
• Preoperative Period MeSH
• Prognosis MeSH
• Insulin-Like Growth Factor Binding Protein 2 * blood   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Urologic Neoplasms surgery   blood   pathology   mortality   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH