Cancer Of Upper Urinary Tract Research Articles

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.

Diagnostic Performance and Interobserver Agreement of Diuretic 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Upper Urinary Tract Cancer.

Previous reports attempted to evaluate bladder cancer using 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) by washing out the excreted FDG with a diuretic. The purpose of this study was to evaluate the value of diuretic FDG PET/plain CT (drtPET/CT) and diuretic FDG PET/contrast-enhanced CT (drtPET/ceCT) in the assessment of upper urinary tract cancers. A total of 66 patients underwent drtPET/CTfor suspected upper urinary tract cancer (UUTC). The study targeted 29 patients who were strongly suspected of having UUTC and underwent magnetic resonance imaging (MRI) of the upper urinary tract. A total of 29 (24 male, five female) patients, with a mean ± SDage of 73 ± 3 (range, 43-84) years, had a suspected neoplasm in the upper urinary tract. They underwent FDG PET/plain and contrast-enhanced CT before and after a diuretic and MRIincluding diffusion-weighted imaging (DWI). A urologist and a physician board-certified in nuclear medicine and radiology independently interpreted the standard PET/CT (stdPET/CT), drtPET/CT, drtPET/ceCT, ceCT, and MRI with DWI images. Interobserver agreement and the diagnostic performance of each modality were evaluated. The kappa values of stdPET/CT, drtPET/CT, drtPET/ceCT, ceCT, and MRI were 0.381, 0.567, 0.7031, 0.448, and 0.185, respectively, with drtPET/ceCT showing the highest kappa value and the only one with good interobserver agreement (>60%). The area under the curve of drtPET/ceCT was 0.92, which was significantly higher than those of stdPET/CT (P=0.027) and MRI (P=0.047). In the present study, drtPET/ceCT had the best diagnostic performance and the highest interobserver agreement for detecting upper urinary tract urothelial cancers.

Efficacy of avelumab maintenance therapy for advanced urothelial carcinoma with histologic subtype and divergent differentiation: a multicenter retrospective study conducted by the Uro-Oncology Group in Kyushu.

The subtype of urothelial carcinoma (SUC) has been known to possess morphological diversity for histologic subtype or divergent differentiation. However, the efficacy of avelumab against SUC remains unclear. Therefore, the effect of the treatment as well as the survival results of avelumab monotherapy were evaluated as a first-line therapeutic maintenance in patients with advanced SUC. A retrospective analysis was conducted on consecutive patients from the Uro-Oncology Group in Kyushu study population with advanced lower and upper urinary tract cancer who underwent avelumab maintenance therapy without progression after first-line platinum-based chemotherapy. Patients with pure urothelial carcinoma (PUC) and SUC were comparatively analyzed based on objective response rate (ORR), disease control rate, progression-free survival (PFS), and overall survival (OS). Out of 49 recorded patients, 38 and 11 had PUC and SUC, respectively. The most common subtype element was glandular differentiation (n=5), followed by squamous differentiation (n=3), micropapillary (n=1), and plasmacytoid subtypes (n=1). The SUC and PUC groups had comparable ORR (0% vs. 2.6%, P>0.99) and disease control rates (54.5% vs. 44.7%, P=0.73). These patient groups also showed no significant difference in PFS (median 3.9 vs. 3.1 months, P=0.33) or OS (median 16.7 vs. 22.1 months, P=0.47). The response of SUC and PUC to avelumab was comparable in patients with advanced lower and upper urinary tract cancer, indicating that avelumab maintenance therapy is also effective for SUC.

Organ-Specific Tumor Response to Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

IntroductionTo evaluate the organ-specific therapeutic effect of enfortumab vedotin (EV) after chemotherapy and immunotherapy failed for advanced urothelial carcinoma. Materials methodsAt 6 institutions between December 2021 and July 2023, we retrospectively analyzed patients with metastatic upper and lower urinary tract cancer who received EV monotherapy after platinum-based chemotherapy and immune checkpoint blockade therapy. Objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1. ResultsThis study analyzed 58 patients with 210 tumor lesions, of which 24% were females and 48% had upper urinary tract cancer. The ORR and disease control rate were 53.5% and 74.1%. Moreover, we found 15 target lesions in the primary site, 7 in local recurrence, 93 in the lymph nodes, 46 in the lung, 29 in the liver, and 20 in the bone, with OSRRs of 40%, 71.4%, 61.1%, 70.6%, 90.9%, and 18.2%, respectively. Over time from baseline, the reduction rate (median) in tumor burden was 50% or more in the lymph node, lung, and liver metastases. ConclusionThe organ-specific tumor response to EV in patients with metastatic urothelial carcinoma was almost favorable. The antitumor activity of EV monotherapy may be less in bone metastasis than in other organ sites. Conversely, EV showed remarkably high efficacy against liver metastasis.

Incidence and molecular characteristics of deficient mismatch repair conditions across nine different tumors and identification of germline variants involved in Lynch-like syndrome

BackgroundBased on molecular characteristics, deficient DNA mismatch repair (dMMR) solid tumors are largely divided into three categories: somatically MLH1-hypermethylated tumors, Lynch syndrome (LS)-associated tumors, and Lynch-like syndrome (LLS)-associated tumors. The incidence of each of these conditions and the corresponding pathogenic genes related to LLS remain elusive.MethodsWe identified dMMR tumors in 3609 tumors from 9 different solid organs, including colorectal cancer, gastric cancer, small-bowel cancer, endometrial cancer, ovarian cancer, upper urinary tract cancer, urinary bladder cancer, prostate cancer, and sebaceous tumor, and comprehensively summarized the characterization of dMMR tumors. Characterization of dMMR tumors were performed as loss of at least one of MMR proteins (MLH1, MSH2, MSH6, and PMS2), by immunohistochemistry, followed by MLH1 promotor methylation analysis and genetic testing for MMR genes where appropriate. Somatic variant analysis of MMR genes and whole exome sequencing (WES) were performed in patients with LLS.ResultsIn total, the incidence of dMMR tumors was 5.9% (24/3609). The incidence of dMMR tumors and the proportion of the three categorized dMMR tumors varied considerably with different tumor types. One to three likely pathogenic/pathogenic somatic MMR gene variants were detected in 15 out of the 16 available LLS tumors. One patient each from 12 patients who gave consent to WES demonstrated non-MMR germline variants affect function (POLQ or BRCA1).ConclusionsOur data regarding the LS to LLS ratio would be useful for genetic counseling in patients who are suspected to have LS, though the genetic backgrounds for the pathogenesis of LLS need further investigation.

Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy. The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery. Prospective quality assessment of surgeries was performed via central review of intraoperative photographs. Postoperative complications were assessed using the Clavien-Dindo Classification. Data were analysed descriptively. A total of 50 patients received RC and PLND. All patients received neoadjuvant chemo-immunotherapy. The median (interquartile range) number of lymph nodes removed was 29 (23-38). No intraoperative complications were registered. Grade ≥III postoperative complications were reported in 12 patients (24%). Complete nodal dissection (100%) was performed at the level of the obturator fossa (bilaterally) and of the left external iliac region; in 49 patients (98%) at the internal iliac region and at the right external iliac region; in 39 (78%) and 38 (76%) patients at the right and left presacral level, respectively. This study supports the surgical safety of RC and PLND following neoadjuvant chemo-immunotherapy in patients with MIBC. The extent and completeness of protocol-defined PLND varies between patients, highlighting the need to communicate and monitor the surgical template.

Treatment advances improve survival in upper tract urothelial carcinoma

Upper urinary tract cancer is rare among urothelial cancers but its incidence has recently increased. Improved survival is being made possible through advances in surgery and adjuvant treatment.

Efficacy of Platinum-based Chemotherapy in Patients With Metastatic Urothelial Carcinoma With Variant Histology.

Variant urothelial carcinoma (VUC, defined herein as urothelial carcinoma with any histological variant) is frequently observed at an advanced stage. However, the efficacy of systemic chemotherapy against VUC in metastatic disease has rarely been reported. This study assessed the therapeutic response and survival outcomes of platinum-based chemotherapy as first-line treatment in patients with metastatic VUC. We retrospectively analyzed consecutive patients with metastatic bladder and upper urinary tract cancer who received gemcitabine plus cisplatin (or carboplatin) at the University of Occupational and Environmental Health Hospital between November 2008 and November 2022. Progression-free survival and overall survival were evaluated using the Kaplan-Meier method and Cox proportional hazard models. Out of 131 patients recorded, 86 (65.6%) had pure urothelial carcinoma (PUC) and 45 (34.4%) had VUC. The most common variant element was squamous differentiation (44.4%). Compared to those with PUC, patients with VUC showed a comparable objective response rate (33.3% vs. 41.9%, p=0.451) and disease control rate (64.5% vs. 75.6%, p=0.221). They also had poorer progression-free survival (median=4.9 months vs. 7.9 months, p=0.014) and overall survival (median=10.9 months vs. 18.2 months, p=0.037) than those with PUC. On multivariate analysis, VUC was an independent predictor of progression (hazard ratio=1.79; 95% confidence interval=1.19-2.69; p=0.005) and mortality (hazard ratio=1.64; 95% confidence interval=1.08-2.48; p=0.020). Although the response of metastatic VUC to platinum-based chemotherapy was not inferior to that of PUC, VUC had progressed faster than PUC. VUC was significantly associated with a poor prognosis after platinum-based chemotherapy as first-line treatment.

Reproductive factors in the risk of bladder cancer and upper urinary tract cancer: The Japan Public Health Center-based Prospective Study.

Reproductive factors are hypothesized to play a role in the incidence of bladder cancer (BC) and upper urinary tract cancer (together, urothelial cancer (UC)). However, evidence regarding these associations is limited, particularly in Asian populations. We analyzed data from 55,882 females aged 40-69 years, and performed Cox proportional hazards regression analyses with three types of adjustment, namely age; reproductive factor of interest and covariates in addition to age (conventional model); and other reproductive factors in addition to the multivariable adjusted model (reproductive model). During an average of 20.2 years of follow-up, 194 UC cases (145 BC cases and 49 UUTC cases) were identified. Early age at natural menopause (<44 years, compared to 49-51 years) increased BC risk in the reproductive model (HR=2.09 (95% CI=1.04-4.20)). An association between UC/BC and age at menopause, including both natural and surgical/induced, was significant in the reproductive model [HR=1.74 (95% CI=1.09-2.77), and HR=1.94 (95% CI=1.15-3.28), respectively]. Early age at natural menopause was suggested to increase UC risk in the reproductive model (HR=1.78 (95% CI=0.93-3.42)). Our findings suggest a significant association between age at menopause and incidence of UC/BC among Asian populations. This study aids understanding the role of reproductive factors in UC/BC incidence. In Japanese populations, age at menopause is suggested to be associated with UC/BC incidence, especially regarding early natural menopause.

Efficacy of Pembrolizumab in Patients With Variant Urothelial Carcinoma: A Multicenter Retrospective Study.

Although variant urothelial carcinoma (VUC, defined here as urothelial carcinoma with any histological variant) is a clinically aggressive disease, the efficacy of pembrolizumab against VUC is not well characterized. This study assessed the therapeutic response and survival outcomes in patients with advanced VUC treated with pembrolizumab for unresectable recurrent or metastatic disease. We retrospectively evaluated 103 patients with advanced bladder and upper urinary tract cancer who received pembrolizumab after failure of platinum-based chemotherapy at 6 institutions between January 2018 and June 2021. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with VUC. We identified 81 and 22 patients with PUC and VUC, respectively. Squamous differentiation (n=14) was the most common variant element, followed by glandular differentiation (n=3) and micropapillary variant (n=3). Baseline characteristics were comparable between the groups. Patients with VUC showed significantly better ORR (59.1% vs. 29.6%, P=.014) and comparable DCR (68.2% vs. 49.4%, P=.150) compared to those with PUC. There were no significant differences between the PUC and VUC groups with respect to PFS (median 5.0 months vs. 10.4 months, P=.222) or OS (median 13.5 months vs. 23.8 months, P=.497). Response of VUC to pembrolizumab was not inferior to that of PUC in patients with advanced-stage bladder and upper urinary tract cancer.

Pathological Significance and Prognostic Role of WWC1 in Upper Urinary Tract Urothelial Cancer.

WW and C2 domain-containing 1 (WWC1) protein is a suppressor of malignancies. However, there is no information on the pathological significance of WWC1 in upper urinary tract cancer (UTUC). In this study, WWC1 immunoreactivity was investigated in 152 non-metastatic UTUC samples. The relationships between WWC1 expression and grade, pT stage, proliferative index (using an antibody to Ki-67), and the immunohistochemical expression of matrix metalloproteinase (MMP)-2 and -9 were evaluated. WWC1 expression was negatively associated with tumor grade and pT stage (p<0.001). Positive expression of WWC1 was a better predictor of the UTUC recurrence and subsequent metastasis, and the multivariate analysis showed that WWC1 expression was a significant predictor of subsequent metastasis (hazard ratio=0.29, p=0.020). WWC1 expression inversely correlated with the proliferative index (odds ratio=2.59, p=0.023) and expression of MMP9 (odds ratio=2.19, p=0.040) but not with MMP2 expression, by multivariate analyses. WWC1 expression was negatively associated with malignant aggressiveness via the suppression of cancer cell proliferation and MMP9 expression in patients with UTUC. This suggests WWC1 to be a useful predictor and novel therapeutic target in patients with UTUC.

Influence of the Coronavirus Disease 2019 Vaccine on Drug Therapy for Urological Cancer.

We investigated whether coronavirus disease 2019 (COVID-19) vaccination and its adverse events would cause cancer treatment of patients with urological cancer to be postponed or changed. We collected COVID-19 vaccination information including adverse events from the medical records of 214 patients with urological cancer receiving cancer drug therapy. The cancer types were renal cancer in 40 cases (18.7%), upper urinary tract cancer in 10 cases (4.7%), bladder cancer in 21 cases (9.8%), prostate cancer in 140 cases (65.4%), and others in 3 cases (1.4%). Of the 214 patients, 178 (83.2%) had received the second dose of the vaccine. Out of 180 vaccinated patients, some adverse events were observed in 69 (38.3%). Vaccination rates for males and females were 85.4% (169/198) and 68.8% (11/16), respectively, and were not significantly different (p=0.081). The incidence of adverse events was significantly higher in females [72.7% (8/11)] than in males [36.1% (61/169)]; p=0.015. Treatment was modified in 11 vaccinated patients; postponed or changed at the discretion of the attending physician in 8 cases, skipped at the discretion of the patient in 1 case, and postponed due to side effects of the immune checkpoint inhibitor in 1 case. Treatment for one patient with upper urinary tract cancer on pembrolizumab was postponed for three weeks due to adverse events of the vaccine. Only 0.6% of the adverse events of the vaccine required postponement of treatment, suggesting that vaccination is safe even during cancer drug therapy.

A0288 - Clinical performance of Xpert Bladder Cancer test in patients with upper urinary tract cancer: Results and possibilities for future use

A0288 - Clinical performance of Xpert Bladder Cancer test in patients with upper urinary tract cancer: Results and possibilities for future use

The Impact of Socioeconomic Inequality on Urological Cancer

Purpose: Socioeconomic inequality may contribute to different risk factors for cancers. This study aims to analyze the socioeconomic patterns of urological cancer incidence and mortality in Taiwan. Materials and Methods: Using data from the National Health Insurance, we designed a retrospective longitudinal cohort study of 3686 subjects who were newly diagnosed with bladder cancer (BC), kidney cancer (KC), and upper urinary tract cancer (UTUC) between 2000 and 2010. We analyzed patients' characteristics and mortality among the three cancers. Results: The average age of KC diagnosis was the youngest among the cancers. Moreover, KC tends to occur in patients with higher-income occupations who reside in urban areas. Both BC and UTUC were much more prevalent in patients with less socioeconomic means and those living in rural areas. Varied comorbidities showed different distributions among urological cancers. Although the extent was most prominent in KC, both overall mortality and cancer-specific mortality of the three cancers increased every year during the follow-up period. Conclusion: Our results demonstrate different patient characteristics and mortality among BC, KC, and UTUC in Taiwan.

A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2\u2032-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients

BackgroundDNA adducts, covalent modifications to DNA due to exposure to specific carcinogens, cause the mispairing of DNA bases, which ultimately results in DNA mutations. DNA methylation in the promoter region, another type of DNA base modification, alters the DNA transcription process, and has been implicated in carcinogenesis in humans due to the down-regulation of tumor suppressor genes. Difficulties are associated with demonstrating the existence of DNA adducts or chemically modified bases in the human urological system. Apart from aristolochic acid-DNA adducts, which cause urothelial carcinoma and endemic nephropathy in a particular geographical area (Balkan), limited information is currently available on DNA adduct profiles in renal cell carcinoma and upper urinary tract urothelial carcinoma, including renal pelvic cancer and ureteral cancer.MethodTo elucidate the significance of DNA adducts in carcinogenesis in the urothelial system, we investigated 53 DNA adducts in the non-tumoral renal parenchyma and non-tumoral renal pelvis of patients with renal cell carcinoma, upper urinary tract urothelial carcinoma, and other diseases using liquid chromatography coupled with tandem mass spectrometry. A comparative analysis of tissue types, the status of malignancy, and clinical characteristics, including lifestyle factors, was performed.ResultsC5-Methyl-2′-deoxycytidine, C5-hydroxymethyl-2′-deoxycytidine (5hmdC), C5-formyl-2′-deoxycytidine, 2′-deoxyinosine, C8-oxo-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine (8-OHdG) were detected in the renal parenchyma and renal pelvis. 8-OHdG was more frequently detected in the renal pelvis than in the renal cortex and medulla (p = 0.048 and p = 0.038, respectively). 5hmdC levels were significantly lower in the renal pelvis of urothelial carcinoma patients (n = 10) than in the urothelium of patients without urothelial carcinoma (n = 15) (p = 0.010). Regarding 5hmdC levels in the renal cortex and medulla, Spearman’s rank correlation test revealed a negative correlation between age and 5hmdC levels (r = − 0.46, p = 0.018 and r = − 0.45, p = 0.042, respectively).ConclusionsThe present results revealed a reduction of 5hmdC levels in the non-tumoral urinary tract mucosa of patients with upper urinary tract urothelial carcinoma. Therefore, the urothelial cell epithelia of patients with upper urinary tract cancer, even in non-cancerous areas, may be predisposed to urothelial cancer.

Extracorporeal Shock Wave Enhances the Cisplatin Efficacy by Improving Tissue Infiltration and Cellular Uptake in an Upper Urinary Tract Cancer Animal and Human-Derived Organoid Model.

Simple SummaryChemotherapy is the standard treatment for advanced upper urinary tract urothelial carcinoma (UTUC), and shock wave treatment is a common strategy for upper urinary tract stones. We explored the mechanism of the combination therapy of low-energy shock waves (LESWs) and cisplatin for UTUC in vitro, in vivo, and in patient-derived organoid (PDO) models. Histopathological examination showed more deteriorated cell arrangement and oedema in the combination treatment group than in the cisplatin only group. Immunohistochemical analysis revealed reduced expression of proliferation markers, increased expression of apoptosis markers, and increased cisplatin infiltration in the combination treatment group. Western blotting revealed decreased cisplatin efflux and membranous protein levels after shock wave application. Moreover, LESW improved the cytotoxicity of cisplatin in the preclinical PDO model of UTUC. Our findings showed that LESW enhanced the antitumour efficacy of cisplatin in UTUC. Hence, combination therapy could have promising applications for locally advanced UTUC in clinical settings.Upper urinary tract urothelial carcinoma (UTUC) is a relatively rare cancer with a poor prognosis if diagnosed at an advanced stage. Although cisplatin-based chemotherapy is a common treatment strategy, it has a limited response rate. Shock wave lithotripsy is a common treatment for upper urinary tract stones. Low-energy shock waves (LESWs) temporarily increase tissue permeability and enhance drug penetration to the targeted tissue. However, no study has investigated the efficacy of the combination of shock wave lithotripsy and chemotherapy in UTUC. Hence, in this study, we aimed to identify the potential application of the combination of LESW and chemotherapy in UTUC. We evaluated the synergistic effects of LESW and cisplatin in vitro, in vivo, and in patient-derived organoid (PDO) models. Compared with cisplatin alone, the combination treatment caused more significant tumour suppression in vitro and in animal models, without increased toxicity. Histological examination showed that compared with animals treated with cisplatin alone, those who received the combination treatment showed more deteriorated cell arrangement and cell oedema. Moreover, LESW improved the cytotoxicity of cisplatin in the preclinical PDO model of UTUC. Thus, LESW combined with cisplatin is a potential new antitumour strategy for improving the treatment response in locally advanced UTUC.

A Cohort Study on the Prognosis of Patients with Urothelial Carcinoma Using the Miyazaki Urological Cancer Database (MUCD)

Miyazaki Urological Cancer Database (MUCD) is a web-based database containing background, treatment, and prognosis of patients with prostate, renal, and urothelial cancers diagnosed in Miyazaki. We entered information on patients diagnosed with urothelial carcinoma from 2014 to 2018 at 4 of the 17 facilities that diagnose urothelial carcinoma in Miyazaki Prefecture. We analyzed the overall survival for bladder cancer and upper urinary tract cancer, and examined its correlation with the presence of symptoms, urine cytology, and clinical TNM classification. There were 487 patients with urothelial carcinoma, comprising 372 (76%) with bladder cancer and 115 (24%) with upper tract urinary cancer. In the bladder cancer group, 301 (81%) patients had symptomatic disease and 119 (32%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 248 (67%), 94 (26%), 19 (5%) and 11 (3%) patients, respectively. In the upper urinary tract cancers group, 89 (76%) had symptomatic disease and 41 (36%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 45 (39%), 37 (32%), 11 (10%) and 22 (19%) patients, respectively. The 3-year survival rates for bladder and upper urinary tract cancer were 83.4% and 67.8%, respectively. TNM classification (≤T1 vs ≥T2≥) was significantly associated with overall survival (bladder cancer : HR＝7.07, 95% CI＝3.13-16.0, p＜0.0001 ; upper tract urinary cancer : HR＝6.33, 95% CI＝2.13-18.8, p＝0.0009). The prognosis of patients with urothelial carcinoma diagnosed in multiple institutions could be evaluated using MUCD. The clinical T stage was significantly associated with overall survival in patients with bladder cancer and patients with upper urinary tract cancer.

MP20-15 DIGITAL UROLOGIC EDUCATION DURING COVID-19

INTRODUCTION AND OBJECTIVE: COVID-19 has drastically changed didactic residency education. The urologic community displayed its resilience and adaptability by swiftly converting in-person education to webinar events in response to the pandemic. The goal of this study was to analyze the trends of urology webinars since the declaration of the COVID-19 pandemic. METHODS: The official social media accounts for all AUAregistered urology residency and urologic-oncology fellowship programs were systematically searched for webinar listings. All of the free webinars available to the greater urologic community posted between January 1, 2020 and June 1, 2020 were included in this study. Data was abstracted from each webinar including the date of delivery, topic of discussion, and number of speakers. Temporal trends were analyzed via join-point regression modelling. RESULTS: A total of 450 webinars were offered in the initial 18 weeks following the pandemic declaration. A total of 629 speakers from 96 academic institutions were involved in at least one webinar. The mean webinar duration was 58.7 minutes. At the peak of the “webinar frenzy,” a mean of 7.1 webinars/day were offered with 12.7 speakers/day involved. Urologic webinars increased in availability significantly from weeks 1 to 9 and decreased in availability non-significantly from weeks 10 to 18. Urologic-oncology was the most commonly discussed sub-specialty, representing 113 (25.1%) separate lectures with 151 speakers. Urologic-oncology increased in interest significantly over weeks 1 to 9 (AWPC: 110.7%;p<0.001) with a stable trend (AWPC -5.5, p=0.3) from weeks 10 to 18. Prostate cancer (33.9%) was the most discussed subject, followed by bladder cancer (29.5%), kidney cancer (12.5%), testis cancer (8%), upper urinary tract cancer (7.2%) and penile cancer (3.5%). CONCLUSIONS: In conclusion, our analysis demonstrates impressive and immediate reaction of the academic urologic community and specifically, the urologic-oncologic community, to continuing medical education amidst a pandemic. While webinars have some limitations, they have the opportunity to increase educational access across geographical and financial barriers. Time will show if webinars have a permanent role in the future of medical education or if we have witnessed the rise and fall of a “webin-era.”. (Table Presented).

MP38-13 PATHOLOGICAL SIGNIFICANCE OF PERIODONTAL DISEASE IN PATIENTS WITH UROTHELIAL CANCERS: CORRELATION WITH URINARY TRACT RECURRENCE AND OXIDATIVE STRESS

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I (MP38)1 Sep 2021MP38-13 PATHOLOGICAL SIGNIFICANCE OF PERIODONTAL DISEASE IN PATIENTS WITH UROTHELIAL CANCERS: CORRELATION WITH URINARY TRACT RECURRENCE AND OXIDATIVE STRESS Yasuyoshi Miyata, Tomohiro Matsuo, Tsuyoshi Matsuda, Junki Harada, Yuta Mukae, Asato Otsubo, Tsubasa Kondo, Kensuke Mitsunari, Kojiro Ohba, and Hideki Sakai Yasuyoshi MiyataYasuyoshi Miyata More articles by this author , Tomohiro MatsuoTomohiro Matsuo More articles by this author , Tsuyoshi MatsudaTsuyoshi Matsuda More articles by this author , Junki HaradaJunki Harada More articles by this author , Yuta MukaeYuta Mukae More articles by this author , Asato OtsuboAsato Otsubo More articles by this author , Tsubasa KondoTsubasa Kondo More articles by this author , Kensuke MitsunariKensuke Mitsunari More articles by this author , Kojiro OhbaKojiro Ohba More articles by this author , and Hideki SakaiHideki Sakai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002053.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Periodontal disease (PD) involves chronic oral infection and inflammation. In recent years, there is general agreement that PD can affect the pathogenesis and progression of various systemic diseases including malignancies. Moreover, PD leads to the stimulation of oxidative stress in distant organs. The aim of this study was to clarify the pathological roles of PD in patients with urothelial cancer (UC). METHODS: We investigated the relationship between PD and clinicopathological features, outcomes, and oxidative stress in 311 patients with UC (bladder=257, upper urinary tract=54). Patients were divided into the following 3 groups based on the severity of PD: none (n=102), mild (without tooth loss, n=93), and severe (with tooth loss due to PD, n=116). The oxidative stress markers, 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), were analyzed by immunohistochemistry in UC tissues. RESULTS: In the entire cohort, the severity of PD was positively associated with tumor grade (p=0.039), but not with pT stage or metastasis. Kaplan-Meier survival curves showed that patients with severe PD had a significantly higher incidence of urinary tract recurrence (p<0.001), but not of subsequent metastasis or survival. Furthermore, such a significant relationship between PD and urinary tract recurrence was detected in bladder cancer (p<0.001), but not in upper urinary tract cancer (p=0.570). Therefore, when further analyses were performed in non-muscle invasive bladder cancer (NMIBC, n=190), PD was significantly associated with grade, pT stage, and concomitant carcinoma in situ (p=0.473, 0.002, and <0.001, respectively). Univariate analysis showed that severe PD was a significant predictor of urinary tract recurrence and a multivariate analysis model that included all clinicopathological features, supported these findings (hazard ratio=1.55, 95% confidential interval=1.85–5.60, p<0.001). Moreover, the percentage of cells positive for 8-OHdG and MDA expression in NMIBC tissues with severe PD was significantly higher (p<0.001) compared to those with no or mild PD. CONCLUSIONS: Our results showed that severe PD was associated with the malignant potential of bladder cancer. In particular, PD played important roles in malignant aggressiveness, including urinary tract recurrence in NMIBC. In addition, we propose that the increase in oxidative stress in bladder cancer tissues caused by PD is associated with such pathological mechanisms. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e699-e699 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuyoshi Miyata More articles by this author Tomohiro Matsuo More articles by this author Tsuyoshi Matsuda More articles by this author Junki Harada More articles by this author Yuta Mukae More articles by this author Asato Otsubo More articles by this author Tsubasa Kondo More articles by this author Kensuke Mitsunari More articles by this author Kojiro Ohba More articles by this author Hideki Sakai More articles by this author Expand All Advertisement Loading ...

The prognostic role of steroid hormone receptor signaling pathways in urothelial carcinoma.

Emerging preclinical or clinical evidence suggests a vital role of nuclear receptor-mediated signals in modulating urothelial carcinogenesis and cancer growth. These include, but are not limited to, androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, and peroxisome proliferator-activated receptors, as well as orphan receptors. In particular, immunohistochemical studies in surgical specimens have demonstrated that increased or decreased expression of steroid hormone receptors, as well as alterations of their upstream or downstream signaling pathways, is often associated with oncologic outcomes in patients with bladder or upper urinary tract cancer. This review article summarizes and discusses available data indicating that steroid hormone receptors and related signals serve as biomarkers for urothelial tumors which further predict their recurrence and/or progression.