Sarcomatoid Urothelial Carcinoma Arising in Autosomal Dominant Polycystic Kidney Disease: A Case Report and Literature Review.

Autosomal dominant polycystic kidney disease (ADPKD) may be associated with various epithelial malignancies. The most reported ones are papillary renal cell carcinoma (RCC) and clear cell RCC. Only one noninvasive urothelial carcinoma arising in the renal pelvis has been previously reported in the setting of ADPKD in the English literature. A 52-year-old patient with ADPKD and a history of renal transplant presented with a poorly differentiated sarcomatoid neoplasm in his native left polycystic kidney. A recognizable urothelial or renal cell carcinoma differentiation was not identified in the resected neoplasm microscopically. The initial diagnosis for this specimen was challenging on morphology and immunohistochemistry, but targeted next-generation sequencing provided molecular evidence in support of urothelial origin, indicating a hotspot mutation -124 C > T in the TERT promoter (C228 T) and loss of heterozygosity on chromosomes 9p and 8p. This tumor is unique because, to our knowledge, this is the first report of upper tract sarcomatoid urothelial carcinoma in a patient with ADPKD.

A new surgical technique of robotic-assisted laparoscopic nephroureterectomy without re-docking in a single position: a single center experience.

A nephroureterectomy conventionally consists of two independent section, which will considerably prolong the operation time. We developed a novel surgical technique for robotic-assisted laparoscopic nephroureterectomy without re-docking in a single position and aimed to access the safety, feasibility, and efficiency of our novel surgical technique. From August 2021 to October 2023, 53 patients who received robotic-assisted laparoscopic nephroureterectomy were retrospectively enrolled in this study. 25 patients underwent traditional nephroureterectomy and 28 patients underwent single-position nephroureterectomy. The basic characteristics of the enroll patients, perioperative parameters, and oncological outcomes were gathered and compared between novel technique robotic surgery group and traditional surgery group. The basic characteristics between two groups had no significantly difference except for the proportion of anticoagulation therapy. The operation time in novel technique robotic surgery group was shorter than that in traditional robotic surgery group, although there was no significant difference (p = 0.403). Lymph-node dissection in novel technique robotic surgery group was obvious more common than that in traditional robotic surgery group (p = 0.037), while the incision length in novel technique robotic surgery group was obviously shorter than that in traditional robotic surgery group (p < 0.001). The oncological outcomes showed no difference between two groups. Compared with traditional robotic-assisted laparoscopic nephroureterectomy, the innovative surgical technique of robotic-assisted laparoscopic nephroureterectomy in a single position showed the advantages of less surgical time, streamlined lymph-node dissection, less trauma, and expedited postoperative recovery, which is worth promoting in clinical practice.

Case report: Toripalimab plus anlotinib in postoperative recurrent renal pelvic sarcomatoid urothelial carcinoma.

Background: Sarcomatoid urothelial carcinoma (SUC) is a rare renal malignancy. Its biological malignancy is high, the prognosis is poor, diagnostic and treatment options are few, and there is no standard treatment plan. Case presentation: In this case, a 64-year-old woman was hospitalized with fever and lower back pain one week previously. The preliminary diagnosis was a right kidney stone with a urinary tract infection. After the anti-infection treatment, a percutaneous right nephrostomy was performed. The intraoperative biopsy (renal pelvis) finding was infiltrating urothelial carcinoma with a sarcomatoid variation. Subsequently, radical surgery was performed for cancer of the right renal pelvis. Implant metastasis of the abdominal wall and adjacent abdominal cavity occurred half a month after the surgery. The lesion was resected again, and two cycles of doxorubicin plus carboplatin chemotherapy were administered. However, the disease progressed more rapidly after the chemotherapy. With the written consent of the patient, the treatment was altered to targeted immune therapy with toripalimab plus anlotinib. A clinical cure was achieved after nine cycles of treatment with no obvious lesions on imaging. The maintenance therapy was administered consecutively for over a year, and the patient is at present still in good condition with a disease-free survival exceeding two years. Conclusion: This case proves that the combination of toripalimab and anlotinib is effective in the treatment of recurrent renal SUC. To the best of our knowledge, this is the first reported case of a patient with advanced recurrent urothelial carcinoma of the renal pelvis sarcomatoid cured with this therapy.

Survival Outcomes by Race Following Surgical Treatment for Upper Tract Urothelial Carcinoma.

OBJECTIVE: Discrepancies in survival outcomes of various genitourinary tract malignancies have been documented across different racial and ethnic groups. Here we sought to examine long-term survival outcomes of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU) when stratified by race. METHODS: A multicenter retrospective analysis using the ROBUUST (ROBotic surgery for Upper tract Urothelial cancer Study) registry identified patients undergoing RNU for UTUC between 2015 and 2022 at 12 centers across the United States, Europe, and Asia. Patients were stratified by race (white, black, Hispanic, and Asian) and primary outcomes of interest-including recurrence-free survival (RFS), metastasis free survival (MFS) and overall survival (OS) - were assessed using univariate analysis, multivariate Cox regression modeling, and Kaplan-Meier analysis. RESULTS: 1446 patients (white n = 652, black n = 70, Hispanic n = 87, and Asian n = 637) who underwent RNU for treatment of the UTUC were included in our analysis. Cox regression modeling demonstrated pathologic nodal staging to be a significant predictor of RFS (HR 2.25; P = .0010), MFS (HR 2.50; P = .0028), and OS (HR 5.11; P < .0001). When using whites as the reference group, there were no significant differences in RFS, MFS, or OS across racial groups. CONCLUSIONS: Unlike other genitourinary tract malignancies, our study failed to demonstrate a survival disadvantage among minority racial groups with UTUC who underwent RNU. Furthermore, a significant difference in RFS, MFS, and OS was not identified across whites, blacks, Asians, or Hispanics with UTUC who underwent RNU.

Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer.

BACKGROUND: Molecular profiling in upper tract urothelial carcinoma (UTUC) with synchronous or metachronous urothelial bladder cancer (UBC) is scarce. We intended to assess immunohistochemical (IHC) and genetic differences between UTUC-only and UTUC with synchronous or metachronous UBC (UTUC + UBC) and evaluate the effect of subsequent UBC on the outcome of UTUC patients stratified by luminal-basal subtypes. METHODS: A retrospective cohort of UTUC was divided into UTUC-only (n = 71) and UTUC + UBC (n = 43). IHC expression of cytokeratin 5/6 (CK5/6), CK20, GATA3, and p53 was evaluated to assess relevant subtypes. Genetic characterization comprised TERTp, FGFR3, RAS, and TP53 status. Kaplan-Meier and Cox regression analyses estimated the effect of clinicopathological variables and molecular profiles on progression-free survival (PFS) and overall survival (OS) of UTUC patients. RESULTS: No meaningful differences were detected among both subgroups according to luminal-basal stratification and genetic analysis. UTUC + UBC was independently associated with a worse PFS when stratified by luminal-basal phenotype (HR 3.570, CI 95% 1.508-8.453, p = 0.004) but with no impact in OS (HR 1.279, CI 95% 0.513-3.190, p = 0.597). CONCLUSIONS: This study reveals that both subgroups exhibited equivalent genomic features and luminal-basal subtypes. The involvement of the bladder relates to shorter PFS but does not seem to influence the survival outcome of UTUC, independently of the IHC phenotype.

Disitamab vedotin (RC48) long-term regimen in a post-nephroureterectomy patient with metastases: a case report.

Background: For patients with metastatic upper tract urothelial carcinoma (UTUC), the preferred first-line treatment is platinum-based chemotherapy. Immunotherapy can be considered a subsequent treatment if the chemotherapy is ineffective or the disease progresses. However, how should treatment be administered if immunotherapy is useless and the patient cannot take chemotherapy? Especially in patients who have metastasized after radical nephroureterectomy (RNU). Case presentation: A 68-year-old woman was admitted to the hospital due to left flank pain for two weeks and was diagnosed with metastatic UTUC after RNU. The patient underwent systemic chemotherapy with gemcitabine and cisplatin (GC), as well as reduced-dose GC, but developed myelosuppression. Immunotherapy was ineffective, so Disitamab vedotin (RC48) was chosen. Results: Disitamab vedotin (RC48) monotherapy was administered for 13 cycles, during which thyroid function remained normal, the patient responded well to the treatment, and the disease was controlled well. In the subsequent two years of follow-up, there was no disease recurrence. Conclusion: The long-term treatment regimen with RC48 is feasible for metastatic UTUC after RNU, and RC48 monotherapy is suitable as first-line therapy for selected patients.

Statin therapy and upper tract urothelial carcinoma risk in hyperlipidemic patients with chronic kidney disease and end-stage kidney disease, a population-based 17-year follow-up study.

BACKGROUND: The upper tract urothelial carcinoma (UTUC) risk associated with statin therapy in hyperlipidemic patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) remains obscure. AIM: This retrospective cohort study investigated the UTUC risk for hyperlipidemic patients with CKD or ESKD associated with statin therapy. METHODS: From the national insurance claims data of Taiwan, we identified hyperlipidemic patients and established three pairs of statin users and non-users sub-cohorts matched by propensity scores: 401,490 pairs with normal kidney function, 37,734 pairs with CKD, and 6271 pairs with ESKD. Incidence rates and hazard ratio (HR) of UTUC were estimated, by the end of 2016, between statin and non-statin cohorts, and between hydrophilic statins users and lipophilic statins users. Time-dependent model estimated adjusted HR, and sub-distribution HR (sHR) accounting for the competing risk of deaths. RESULTS: The statin-users with ESKD were at increased UTUC risk (sHR 1.98; 95% confidence interval (CI), 1.28-3.06), significant for younger patients (40-64 years). The incidence was twofold greater in women than in men (31.8 versus 15.9 per 10,000 person-years). Receiving lipophilic statins was associated with increased UTUC risk in CKD and ESKD patients, while receiving hydrophilic statins was associated with increased UTUC risk in ESKD patients. CONCLUSIONS: Patients with ESKD receiving statin were at an increased UTUC risk, significant for younger group (<65 y/o). The positive associations between UTUC and statin persisted in both genders with ESKD, and in therapy with either lipophilic statins or hydrophilic statins. Statin users with ESKD deserve attention for UTUC prevention.

A nomogram for overall survival of second primary cancers following upper-tract urothelial carcinoma: a SEER population-based study.

Background: With improving prognosis in upper-tract urothelial carcinoma (UTUC), an increasing number of second primary malignancies (SPMs) are being identified. However, there is limited research on SPMs following UTUC. This study aims to evaluate the risk of SPMs in UTUC patients and create a nomogram to predict their survival rates. Methods: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database, we assessed the risk of SPMs among UTUC patients. Additionally, we developed and validated an overall survival (OS) nomogram for SPM patients post-UTUC diagnosis. Results: The prevalence of SPMs among UTUC patients was 30.23%, with solid tumors being the most prevalent type of second malignancy, constituting 95.30% of all SPMs. The overall risk of SPMs was significantly elevated across all subgroups. Univariate and multivariate Cox regression analyses identified age, race, gender, UTUC SEER historic stage, surgery, SPM site, histologic type, grade, and SEER historic stage as independent prognostic factors for SPM OS. Subsequently, we developed a nomogram for predicting SPM OS. The C-index for the training and validation sets were 0.72 [95% confidence interval (CI): 0.70-0.74] and 0.71 (95% CI: 0.67-0.75), respectively. The area under the curve (AUC) demonstrated good performance of our model in predicting the 3-year (0.73 and 0.737) and 5-year (0.723 and 0.733) OS of SPMs in both sets. Conclusions: This study represents the first comprehensive analysis of SPM incidence in UTUC patients and introduces a nomogram for predicting SPM prognosis.

Urothelial cancer: state of art in Ukraine and improvement pathways.

Aim: This study aims to assess the effectiveness of urothelial cancer treatment in Ukraine, utilizing population-based data from the National Cancer Registry. The primary goal is to evaluate trends and approaches to therapy, with a focus on overall survival rates in patients with urothelial tumors. Materials and methods: A retrospective cross-sectional analysis was conducted based on the National Cancer Registry, involving 12 698 patients (2008-2020) with urothelial tumors of the upper urinary tract (UTUC) and bladder cancer (BC) who underwent surgical treatment. Demographic indicators, surgical interventions, complications, and survival rates were analyzed. Results: The average age for all patients was 70 years. The number of patients undergoing radical treatment was 1820 (15%) among BC and 573 (59%) among UTUC. The 30-day readmission rate was low for both, with a slightly higher preference for UTUC (2.3 vs. 4.6%). Whereas grade III or higher Cl-Dindo complications were seen in only 0.2% of cases. Notable findings include low frequency of neoadjuvant (7%) and adjuvant chemotherapy (28%) among patients with invasive urothelial carcinomas. Median eGFR for invasive UTUC before and after surgery was 63.2 and 51.4 ml/min, respectively (P=0.00054). The directly opposite trend was seen in BC-61.2 and 68.7 ml/min, respectively (P=0.0026).For BC, the overall survival rates by stages were: I-73%, II-49%, III-18%, and IV-11% (χ2=1807.207; P=0.000001). As for UTUC, the 5-year overall survival rates corresponded to the literature data, but there was a pronounced negative trend towards a decrease in this indicator after a 10-year period for all stages (χ2=146.298; P=0.000003). Conclusion: The study emphasizes the importance of effective systemic treatments, adherence to treatment guidelines, and the need for multidisciplinary consultations among Ukrainian patients with urothelial cancer.

Blood-, Tissue- and Urine-Based Prognostic Biomarkers of Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) is a rare but aggressive neoplasm. Currently, there are few reliable and widely used prognostic biomarkers of this disease. The purpose of this study was to assess the prognostic value of blood-, tissue- and urine-based biomarkers in patients with UTUC. A comprehensive literature search was conducted using the PubMed, Cochrane and Embase databases. Case reports, editorials and non-peer-reviewed literature were excluded from the analysis. As a result, 94 articles were included in this review. We evaluated the impact of 22 blood-based, 13 tissue-based and 4 urine-based biomarkers and their influence on survival outcomes. The neutrophil-lymphocyte ratio, albumin, C-reactive protein, De Ritis ratio, renal function and fibrinogen, which are currently mentioned in the European Association of Urology (EAU) guidelines, are well researched and most probably allow for a reliable prognosis estimate. However, our review highlights a number of other promising biomarkers that could potentially predict oncological outcomes in patients with UTUC. Nonetheless, the clinical value of some prognostic factors remains uncertain due to the lack of comprehensive studies.

Exploring Radiotherapy as a Promising Alternative for Managing Advanced Upper Tract Urothelial Carcinoma: Rescuing Chemotherapy-Intolerant Patients.

PURPOSE: To investigate the safety and effectiveness of radiotherapy for advanced upper tract urothelial carcinoma (UTUC) patients intolerant to chemotherapy. METHODS: Data for 21 patients with advanced UTUC intolerant to chemotherapy were retrospectively collected. All patients were treated with conventionally fractionated radiotherapy (50-70 Gy/20-33 f) or partial-SABR boost to the lesions (50-60 Gy/20-25 f with tumor center boosted with 6-8 Gy/f, 3-5 f) for bulky tumors. RESULTS: The median age was 75 years (range, 58-87 years). Primary tumor resection was performed for all patients and none underwent metastatic resection. Seventeen (81%) patients had oligometastasis (1-5 metastases) at diagnosis. Eighteen (85.7%) received irradiation to all tumor lesions. Lymph node metastasis was predominant in the whole group (17/21). Other lesions were distributed as local recurrence (7/21), bone metastases (2/21) and abdominal wall/muscle (2/21). The median follow-up time was 38.5 months (interquartile range, 15.2-48.7 months). Rate of local control (LC), progression-free survival (PFS) and overall survival (OS) of the whole group at 1 year were 90%, 46.6%, and 80.4%, respectively. At 3 years, LC, PFS and OS were 65.6%, 26.6%, and 40.9%, respectively. Fourteen patients developed acute mild gastrointestinal toxicity, generally of grade 1-2; 8 patients developed acute grade 1-2 hematological toxicity, consisting mainly of anemia and leukopenia. No grade 3 or higher acute or late toxicities were observed. CONCLUSION: For patients with advanced UTUC who are not able to tolerate chemotherapy, radiotherapy is a safe treatment and can achieve good local tumor control.

5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data.

BACKGROUND: Increasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. METHODS: The MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. RESULTS: Overall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58-1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87-1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. CONCLUSIONS: The use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

Clinical Significance of Tumor Location for Ureteroscopic Tumor Grading in Upper Tract Urothelial Carcinoma.

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.

Bilateral nephrolithiasis and upper tract transitional cell carcinoma in horseshoe kidney.

Nephroureterectomy is currently the criterion-standard treatment for high-grade upper tract urothelial carcinoma (UTUC). Current guidelines and expert opinions propose some exceptions to this approach based on patient characteristics, disease status, and function of the contralateral kidney. We present a rare case of a patient with horseshoe kidney, bilateral large nephrolithiasis, high-grade UTUC in one moiety, and relative parenchymal thinning of the contralateral side. The patient was treated with a percutaneous, minimally invasive, nephron sparing approach. The patient also had intracollecting system instillations of gemcitabine and docetaxel. Minimally invasive percutaneous resection of high-grade UTUC is a safe procedure in select cases. Current guidelines may not apply to all patients; unique scenarios with UTUC may require personalized decision-making and treatment at specialized centers.

Impact of surgical management of upper tract urothelial cancer in octogenarians: A population-based study.

Background: Upper tract urothelial carcinoma (UTUC) is an aggressive disease with a high progression rate. The standardmanagement for this disease is nephroureterectomy. Nephron sparing nonradical surgery is an alternative therapeutic approach. In men with limited life expectancy, the potential harm of UTUC progression must be weighed against surgical morbidity and mortality, and thus, more conservative approaches may be selected. This study aims to investigate the comparative benefits of radical and conservative surgical management in patients older than 80 years with localized UTUC. Materials and methods: A search was conducted in the Surveillance, Epidemiology, and End Results database for patients older than 80 years who were diagnosed with localized (T1-2N0M0) cancer in the renal pelvis or ureter as the only malignancy from 2004 to 2015. Patients were divided into 3 therapeutic groups: no surgery, local intervention (ie, local tumor excision or segmented ureterectomy), and radical surgery (nephroureterectomy). Demographic and cancer-related parameter data were collected. Logistic regression analysis was conducted to investigate predictors for surgical treatment. Kaplan-Meier curves and Cox regression were used to analyze survival outcomes. Results: Data from 774 patients were analyzed, including 205 in the no-surgery group, 181 in the local intervention group, and 388 in the radical surgery group. Older, African American patients with T1 stage disease were less likely to receive surgical treatment. Among surgically treated patients, renal pelvic tumors, and high-grade and T2 stage disease were associated with radical resection. Surgically treated patients had a longer median overall survival (OS) than in those treated nonsurgically (13, 35, and 47 months in no-surgery, local intervention, and radical surgery groups, respectively; p < 0.001). Although surgically treated patients demonstrated higher 5-year OS (8.8% [no surgery], 23.2% [local intervention], and 23.5% [radical surgery], p < 0.001) and 5-year disease-specific survival (DSS) (41.0%[no surgery], 69.1%[local intervention], and 72.9%[radical surgery]; p < 0.001) than in those treated nonsurgically, no significant differences were found between the local intervention and radical surgery groups (p > 0.05). Based on multivariate Cox regression analysis, surgical treatments, including both nonradical and radical resection, were independently associated with improved OS and DSS after controlling for age, marital status, tumor grade, and radiation status. Conclusions: Patients older than 80 years with localized UTUC who undergo surgery demonstrate longer survival. Radical and nonradical resections seemto have similar OS and DSS outcomes. Thus, when clinically indicated in this population, a more conservative surgical approach may be reasonable.

A urine-based liquid biopsy for detection of upper tract urothelial carcinoma: a self-matched study.

BACKGROUND: To establish the pathological diagnosis of UTUC before treatment is profitable. At present, the conventional pathological diagnostic methods have certain problems. Besides, the urine-based DNA methylation test have been already utilized to detect bladder cancer. OBJECTIVE: To evaluate the sensitivity and specificity of DNA methylation plus 17 genes mutation test and compare the combined test with cytology. MATERIALS AND METHODS: We included 45 patients from April 2019 to May 2022, all of whom underwent radical nephroureterectomy (RNU), nephrectomy, diagnostic ureteroscopy or tissue biopsy. Before surgery, the urine samples were collected for DNA methylation plus 17 genes mutation test and cytology. The test performance was calculated, and comparative ROC curves were drawn. RESULTS: The median age of the patients was 67 years. The Kappa value of the DNA methylation plus 17 genes mutation test and tissue pathology was 0.59 (p<0.001). The sensitivity/specificity/PPV/NPV of DNA methylation plus 17 genes mutation test was 86/80/94/62% compared with 29/100/100/29% for cytology. The AUC of DNA methylation plus 17 genes mutation test was 0.829 (p<0.001).The mutated gene proportion of UTUC patients was 51.43% for TERT and 25.71% for TP53. CONCLUSION: The test performance of DNA methylation plus 17 genes mutation test was satisfactory, which may replace cytology in the future. Further multicenter studies with larger samples are needed to confirm the clinical value of this promising method. NOVELTY & IMPACT STATEMENTS: We evaluated the diagnostic efficacy of a urine-based liquid biopsy for the detection of UTUC and compared the combined test with cytology. We found satisfactory results and concluded that the test could partly replace cytology. Further studies are needed.

The impact of bladder cuff excision on outcomes after nephroureterectomy for upper tract urothelial carcinoma: An analysis of the ROBUUST 2.0 registry.

OBJECTIVES: We sought to determine whether bladder cuff excision and its technique influence outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS AND MATERIALS: A multicenter, international, retrospective analysis using the ROBotic surgery for Upper tract Urothelial cancer Study (ROBUUST) 2.0 registry identified 1,718 patients undergoing RNU for UTUC between 2015 and 2023 at 17 centers across the United States, Europe, and Asia. Data was gathered on (1) whether bladder cuff excision was performed and (2) what technique was used, including formal excision or other techniques (pluck technique, stripping/intussusception technique) and outcomes. Multivariate and survival analyses were performed to compare the groups. RESULTS: Most patients (90%, 1,540/1,718) underwent formal bladder cuff excision in accordance with EAU and AUA guidelines. Only 4% (68/1,718) underwent resection using other techniques, and 6% (110/1,718) did not have a bladder cuff excised. Median follow up for the cohort was 24 months (IQR 9-44). When comparing formal bladder cuff excision to other excision techniques, there were no differences in oncologic or survival outcomes including bladder recurrence-free survival (BRFS), recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), or cancer-specific survival (CSS). However, excision of any kind conferred a decreased risk of bladder-specific recurrence compared to no excision. There was no difference in RFS, MFS, OS, or CSS when comparing bladder cuff excision, other techniques, and no excision. CONCLUSIONS: Bladder cuff excision improves recurrence-free survival, particularly when considering bladder recurrence. This benefit is conferred regardless of technique, as long as the intramural ureter and ureteral orifice are excised. However, the benefit of bladder cuff excision on metastasis-free, overall, and cancer-specific survival is unclear.

Differential effect of surgical technique on intravesical recurrence after radical nephroureterectomy in patients with upper tract urothelial cancer: a systematic review and Meta-analysis.

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.

Central pathology review and its prognostic value in upper tract urothelial carcinoma patients: a nationwide multi-institutional study.

The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.

Effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk upper tract urothelial carcinoma: a retrospective, real-world study.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare subset of urothelial cancers with poor prognosis. No consensus exists on the benefit of adjuvant immunotherapy for patients with UTUCs after nephroureterectomy with curative intent and the existing studies are limited. Herein, this study aimed to evaluate the effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk UTUC. METHODS: A retrospective study was conducted on 63 patients with high-risk UTUC who received tislelizumab with or without gemcitabine-cisplatin (GC) chemotherapy regimen after surgery between January 2020 and December 2022. Data on demographic and clinical characteristics, surgical, outcomes, prognostic factors, and safety were collected and analyzed. RESULTS: Among the 63 patients with high-risk UTUC, the median age was 66 years (interquartile range 57-72), with 33 (52%) being male. The majority of patients with staged pT3 (44%) and pN0 (78%) disease. Fifty-one patients (81%) received tislelizumab plus GC chemotherapy, and 12 (19%) were treated with tislelizumab monotherapy. After the median follow-up of 26 months (range 1-47), 49 (78%) patients achieved stable disease. The 2-year disease-free survival (DFS) and 2-year overall survival were 78.68% (95% CI: 60.02-87.07%) and 81.40% (95% CI: 68.76-89.31%), respectively. The cycles of GC chemotherapy were independent prognostic factors for survival, with higher DFS (hazard ratio = 0.68, 95% CI, 0.50-0.93; p = 0.016) observed in the subgroup undergoing ≥ 3 cycles versus < 3 cycles of GC chemotherapy. Fifty-eight patients (92%) experienced at least one treatment-related adverse event (TRAE), with grade 3-4 TRAEs occurring in 13%. The most common grade 3-4 TRAEs were decreased white blood cells, thrombocytopenia, and ulcers. CONCLUSIONS: The study demonstrates promising clinical benefits and a manageable safety profile of the tislelizumab-based adjuvant regimen for patients with high-risk UTUC. This suggests that adjuvant immunotherapy represents a potential therapeutic strategy for this population.