Tract Urothelial Cancer Research Articles

Oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma: a literature review.

Radical nephroureterectomy (RNU) represents the gold standard treatment for non-metastatic upper tract urothelial cancer. We sought to provide a comprehensive review of reported oncologic outcomes of the RNU procedure and of factors that might impact these outcomes. A non-systematic review of the literature was conducted by performing an electronic literature search using PubMed with "radical nephroureterectomy" and "oncologic outcomes" as free text search terms. Both original articles and systematic reviews were considered. Search was limited to articles in English that were published in the last 20 years. Open and laparoscopic RNU offer comparable oncologic outcomes. In more recent years, the discussion has de facto shifted towards the "oncological safety" of robotic RNU, which also seems to offer comparable oncologic outcomes. Several studies have looked at the impact of different treatment-, patient- and tumor-related factors. Among treatment-related factors, attention has been given to diagnostic ureteroscopy and the risk of intravesical recurrence. Surgical wait time and perioperative blood transfusion have also been studied. Perioperative chemotherapy, specifically adjuvant therapy, was shown to improve survival. Among patient-related factors, baseline chronic kidney disease, diabetes mellitus, body mass index, and systemic inflammation have gained recent attention. Some tumor related factors, such as stage, grade, location, and multifocality may negatively impact survival outcomes. Lymphovascular invasion and histologic variants are clinically significant pathological findings. RNU is a procedure with measured long-term oncologic outcomes. Minimally invasive techniques have gained an established role as they seem to offer comparable oncologic "safety", although special attention is needed in relation to the method of bladder cuff excision. Robotic RNU is gaining popularity, and while evidence remains limited, the current literature supports the oncologic safety of this procedure. Several factors, which can be categorized as treatment-related, patient-related, and tumor-related, might impact the oncologic outcomes of UTUC patients undergoing RNU. These factors can provide crucial information to stratify patients based on their relative risk of disease recurrence and mortality which may guide clinical decision-making.

First analysis of the safety and efficacy of UGN-101 in the treatment of ureteral tumors

ObjectiveUGN-101 has been approved for the chemoablation of low-grade upper tract urothelial cancer (UTUC) involving the renal pelvis and calyces. Herein is the first reported cohort of patients with ureteral tumors treated with UGN-101. Patients and MethodsWe performed a retrospective review of patients treated with UGN-101 for UTUC at 15 high-volume academic and community centers focusing on outcomes of patients treated for ureteral disease. Patients received UGN-101 with either adjuvant or chemo-ablative intent. Response rates are reported for patients receiving chemo-ablative intent. Adverse outcomes were characterized with a focus on the rate of ureteral stenosis. ResultsIn a cohort of 132 patients and 136 renal units, 47 cases had tumor involvement of the ureter, with 12 cases of ureteral tumor only (8.8%) and 35 cases of ureteral plus renal pelvic tumors (25.7%). Of the 23 patients with ureteral involvement who received UGN-101 induction with chemo-ablative intent, the complete response was 47.8%, which did not differ significantly from outcomes in patients without ureteral involvement. Fourteen patients (37.8%) with ureteral tumors had significant ureteral stenosis at first post-treatment evaluation, however, when excluding those with pre-existing hydronephrosis or ureteral stenosis, only 5.4% of patients developed new clinically significant stenosis. ConclusionsUGN-101 appears to be safe and may have similar efficacy in treating low-grade urothelial carcinoma of the ureter as compared to renal pelvic tumors.

Trends and sex-specific incidence of upper urinary tract cancer in Taiwan: A birth cohort study.

Taiwan has one of the highest incidences of upper tract urothelial cancer (UTUC) worldwide, especially in women; however, no nationwide, long-term follow-up study has evaluated this. We investigated the incidence of UTUC in Taiwan using data from the national population-based Taiwan Cancer Registry database (1985-2019). We divided the birth cohort into nine 5-year age groups and calculated the age-specific incidence for these groups according to the corresponding birth years. The average annual percent change in the incidence of renal pelvis cancer from 1985 to 2019 showed sex-specific differences, with 3.5% and 5.3% increases in the incidences in men and women, respectively. The age-specific incidence rate for renal pelvis cancer among women showed a gradual increase in the group with older women as well as an increase over time in each age group. The results of a birth cohort analysis revealed that younger cohorts had higher incidence rates of renal pelvis cancer than older cohorts did. We demonstrated that the incidence of UTUC is unusually high among older Taiwanese women and that younger cohorts have a high risk of UTUC than older cohorts.

Impact of pathological response on oncological outcomes in patients with upper tract urothelial cancer receiving neo-adjuvant chemotherapy

The purpose of this study is to evaluate the rates of pathological complete response (ypT0N0/X) and pathological response (ypT1N0/X or less) in patients with upper tract urothelial cancer who were treated with neo-adjuvant chemotherapy and to examine their impact on oncological outcomes. This study is a multi-institutional retrospective analysis of patients with high-risk upper tract urothelial cancer who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021. Logistic regression analyses were used to investigate all clinical parameters for response after neoadjuvant chemotherapy. Cox proportional hazard models were performed to assess the effect of the response on the oncological outcomes. A total of 84 patients with UTUC who received neo-adjuvant chemotherapy were identified. Among them, 44 (52.4%) patients received cisplatin-based chemotherapy, and 22 (26.2%) patients had a carboplatin-based regimen. The pathological complete response rate was 11.6% (n=10), and the pathological response rate was 42.9% (n=36). Multifocal tumors or tumors larger than 3cm significantly reduced the odds of pathological response. In the multivariable Cox proportional hazard model, pathological response was independently associated with better overall survival (HR 0.38, p=0.024), cancer-specific survival (HR 0.24, p=0.033), and recurrence-free survival (HR 0.17, p=0.001), but it was not associated with bladder recurrence-free survival (HR 0.84, p=0.69). Pathological response after neo-adjuvant chemotherapy and radical nephroureterectomy is strongly associated with patient survival and recurrence, and it might be a good surrogate for evaluating the efficacy of neo-adjuvant chemotherapy in the future.

Stability of Opened Durvalumab (IMFINZI) Vials. The Beginning of the End of Costly Product Wastage?

Durvalumab is a monoclonal antibody approved for the treatment of lung, urothelial and biliary tract cancers. Durvalumab is supplied in vials as a solution containing no preservatives. Monographs recommend single use of durvalumab vials, and that any leftovers be discarded within 24 h. Thus, significant portions of unused product from opened vials are wasted on a daily basis, generating considerable financial losses. The objective of the present study was to assess the physicochemical and microbiological stability of durvalumab vials kept at 4 °C or room temperature, at 7 and 14 days after opening. Following pH and osmolality measurements, turbidity and submicronic aggregation of durvalumab solution were evaluated by spectrophotometry and dynamic light scattering, respectively. Moreover, steric exclusion high performance liquid chromatography (SE-HPLC), ion exchange HPLC (IEX-HPLC) and peptide mapping HPLC were used to respectively assess aggregation/fragmentation, charge distribution and primary structure of durvalumab. Microbiological stability of durvalumab was evaluated by incubation of vial leftovers on blood agar. All experiments showed physicochemical and microbiological stability of durvalumab vial leftovers for at least 14 days when aseptically handled and kept at either 4 °C or at room temperature. These results suggest the possible extension of utilization of durvalumab vial leftovers well beyond 24 h.

Hypertension Linked to Worse Upper Tract Urothelial Cancer Outcomes

Hypertension Linked to Worse Upper Tract Urothelial Cancer Outcomes

Clinical value of cholinesterase in patients treated with radical nephroureterectomy for upper urinary tract carcinoma

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

Effects of treatment and patterns of metastases in upper tract and bladder urothelial cancer and non-urothelial cancer based on the national cancer database (NCDB) analysis.

e16571 Background: Upper tract Urothelial cancer (UTUC) and bladder urothelial and non-urothelial cancers can have varying patterns of metastases and response to treatment. Given worse response of visceral metastases to current immune checkpoint inhibitors (ICI) and worse outcomes of non-urothelial cancers, understanding the incidence, characteristics and survival for different metastatic presentation would be informative. Methods: The primary objective is to describe characteristics, treatment patterns, evaluate trends and differences in metastatic presentation and survival according to NCDB between upper tract urothelial cancers (UTUC) versus non-urothelial (nUTUC) histologies (squamous, sarcomatoid, small cell or neuroendocrine, adenocarcinoma) and bladder urothelial cancer (UC) and bladder non-urothelial cancer (nUC). Results: Extraction of data from diagnosis between year 2004 – 2017 from the NCDB was performed. A total of 649939 cases of whom UC = 630423 and nUC = 19516 for both bladder and upper tract cancers, respectively, were identified. Median age was 71.4 years (UC) and 70.1 years (nUC), with majority made up of men (62% of UTUC and 75% of bladder UC). Stage distribution at diagnosis was higher in nUC with Stage III at 1711 (8.8%, nUC) compared to 15725 (2.5%, UC) and Stage IV the nUC group (21.9%) compared to UC at 4.6%. Overall survival (OS) was worse with nUC for stage IV cancers with median OS (mOS) of 6.14 mos (95% CI 5.78-6.47) for nUC vs 7.92 mos (95% CI 7.75-8.08) for UC; logrank p &lt; 0.001. Metastatic sites evaluated included bone, brain, liver, lung, and distant lymph nodes. mOS of Patients with visceral metastatic sites of disease are as follows: distant lymph nodes: UC: 7.59 mos (95% CI 6.6- 8.8); nUC: 5.62 mos (95% CI 4.1-7); log-rank p = 0.0372; liver: UC: 3.5 mos (95% CI 2.89-4.1); nUC: 4.1 mos (95% CI 2.6-6.83); p = 0.1874; lung: UC: 5.7 mos (95% CI 5.09-6.37); nUC: 4.27 mos (95% CI 2.99-6.74); p = 0.1567; Brain: UC: 3.06 mos (95% CI 2.1-4.24); nUC: 2.34 (95% CI 1.1-5.3), p = 0.5464. Use of chemotherapy resulted in improved OS in the UC group with mOS of 73.53 mos (95% CI 72.61-74.41) compared to nUC at 17.28 mos (95% CI 16.59-17.87), p &lt; 0.0001 and use of ICI similarly yielded improvement in the UC group with mOS of 115.98 mos (95% CI 114.33-117.65) compared to nUC at 64.49 mos (95% CI 45.67-88.51); p &lt; 0.0001 although radiation therapy resulted in less profound treatment effect with UC at 16.39 mos (95% CI 16.07-16.69) and nUC: 13.01 (95% CI 12.32-13.63); p &lt; 0.0001. Conclusions: While treatment using chemotherapy and ICI has led to improvement in OS in higher stages of disease, patterns of metastases reveals visceral presentation portends a poor prognosis in both urothelial and non-urothelial cancers with slightly better mOS in those with distant lymph nodes as main presentation of metastases.

Upper tract urothelial cancer (UTUC): Role of sequencing, molecular subtyping and treatment outcomes.

e16578 Background: Upper tract urothelial cancers (UTUCs) are rare forms of urothelial cancer that behave in a more aggressive manner. Treatment response to immunotherapy may be less impactful in the adjuvant setting. Studies suggest molecular subtyping might predict survival outcomes. We seek to determine whether genomic sequencing, molecular subtype signatures can be used to predict patient response to chemotherapy in upper tract urothelial cancers. Methods: UTUC patients seen consecutively at a single institution during a 4-year period were evaluated with IRB approval. Analyses of NGS (next-generation sequencing) using Foundation Medicine or TEMPUS platforms were compiled. Decipher Bladder assay (research use only for UTUC) using a transcriptome microarray to characterize tumor specimens as luminal vs. non-luminal and 4 non-luminal subtypes. Retrospective and descriptive analyses were used to identify predictors of response and survival and therapeutic options patients (pts) underwent. Additional phenotypic factors such as initial staging, tumor location, response to neoadjuvant chemotherapy (NAC), and responses to treatment for localized or metastatic disease were determined. Results: UTUC patients whose clinical and demographic features were available for 23 patients (Male = 7; Female = 16); locally advanced = 9; metastatic = 14. Tumor samples were obtained with Decipher bladder assay (n=4); next-generation sequencing assay (n = 9). Neoadjuvant chemotherapy (NAC) was given in all pts with localized disease and for metastatic disease (n=11 pts). Platinum-based chemotherapy (PBC) resulted in median overall survival (mOS) of 36.6 mos compared to no chemotherapy 22.8 mos at the time of data cut-off. Decipher bladder assay showed basal subtype and mixed basal/claudin-low in 4 patients of whom one achieved stable disease though residual ypT3 after NAC and the 3 achieved progressive disease as best response, all with metastatic disease. NGS showed LOH - 21.01% and ATM truncation in 2 patients with prolonged responses to avelumab maintenance immunotherapy and 2 patients with CDK2A/2B loss with prolonged survival (mOS = 16.8 mos). Additionally, 5 patients were identified as having a TERT promoter variant, though this does not appear to have a significant relationship with survival or disease progression when compared to those without the variant. Conclusions: Results do not identify a specific NGS signature or subtype signature that predicts response to chemotherapy in the neoadjuvant or metastatic setting though receipt of chemotherapy appears to clinically affect outcomes in this small sample of UTUC patients. Further studies are needed to identify specific molecular signatures that would predict responses to therapy.

A phase 3 multicenter study to evaluate the safety and efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in treatment of low-grade (LG) upper tract urothelial cancer (UTUC).

TPS4613 Background: Padeliporfin VTP is a combination product: drug, padeliporfin is administered IV and a device, a laser light delivery system, includes a source of light (the laser) that emits near-infrared (NIR) light at 753 nm, and optic fiber that delivers the light to the target lesion(s) in the upper tract urothelium. In Phase 1 NCT03617003 study 19 patients(pts) received up to 2 endoscopic VTP treatments with 6 mos follow-up(FU). Pts with residual or recurrent UTUC (high grade(HG)or LG) who failed prior endoscopic treatment/unable/unwilling to undergo surgery were included. Primary endpoint, Maximum tolerated dose (MTD) of laser light fluence, was identified using dose escalation model with a modified continual reassessment method with increasing light fluence (100-200 mW/cm). Secondary endpoint was efficacy, defined by absence of visible tumor and negative urine cytology 30 days post-treatment. 14(74%) pts received the MTD of 200mW/cm, 2 (11%) of whom experienced DLTs (flank pain grade 2 and 3). Response rate at 30 days was 94% (50% CR, 44% partial). 8 pts received 2nd VTP, with a final observed 68% complete response (CR) rate. Most frequent adverse events: transient flank pain (79%) and hematuria (84%). No treatment-associated ureteral strictures were reported. All patients had preserved kidney at the 6-mos FU(Wesley Yip,2022). Methods: Padeliporfin VTP is being evaluated in a phase 3 study in patients with UTUC LG,100 patients are planned to be enrolled. Enrollment started in Mar 2021 and is ongoing in USA, EU&amp;Israel,3 pts are enrolled. Pts are being treated with padeliporfin VTP in two phases: Induction and Maintenance treatment Phases (ITP and MTP). ITP consists of 1-3 VTPs every 28 days. If CR is not achieved after 1st VTP, up to 2 additional VTPs are allowed. If CR is achieved in the ITP, pts are allowed into the MTP (12 mos). In the MTP VTPs can be provided every 3 mos for pts with recurrent tumor that is deemed treatable, defined as LG with the largest tumor (index) 5 -15 mm, in up to 2 locations in the kidney or one ureter location ≤20 mm. Long Term FU Phase: Pts completing the MTP, will be followed for safety for 48 mos with no VTPs. Primary objective is to demonstrate efficacy and durability of effect of padeliporfin VTP treatment. Secondary objective-evaluation of padeliporfin VTP‐related safety and tolerability. Key inclusion criteria: Up to 2 biopsy-proven LG UTUC tumors with the largest tumor (index) 5-15 mm, located in the calyces, renal pelvis or in the ureter, with no HG cells. Ureter involvement in one location ≤ 20 mm. Key exclusion criteria: Current HG or muscle invasive urothelial bladder cancer . CIS current or previous in the upper urinary tract. History of ≥ T2 urothelial cancer in the past 2 years. DSMB last reviewed the trial in Sep 2022 and suggested the trial continue as planned. Clinical trial information: NCT04620239 .

The patient experience with localized upper tract urothelial cancer

ObjectiveTo understand the experiences of patients with low-grade upper tract urothelial carcinoma via in-depth interviews covering the diagnosis, treatment, and follow-up. MethodsA qualitative study was performed using 60 minutes interviews with patients diagnosed with low-grade UTUC. The participants received either endoscopic treatment (ET), radical nephroureterectomy (RNU) or intracavity mitomycin gel for the pyelocaliceal system. Interviews were conducted by trained interviewers via telephone using a semi-structured questionnaire. The raw interviews were coded into discrete phrases that were grouped together based on similarity of meaning. Inductive data analysis methodology was used. Themes were identified and refined to overarching themes striving to encompass the original meaning and intent of participant's words. ResultsTwenty individuals were enrolled; 6 were treated with ET, 8 were treated with a RNU, and 6 were treated with intracavitary mitomycin gel. The median age was 74 years (52–88) and half of participants were women. Most endorsed good, very good, or excellent health. Four unique themes were identified: 1. Misunderstandings of the nature of disease; 2. Importance of physical symptoms during treatment as a proxy for recovery; 3. Competing desires for kidney preservation versus expeditious treatment; and 4. Trust in doctors and minimal perceived shared decision-making. ConclusionsLow grade UTUC is a disease with a diverse clinical presentation and an evolving landscape of available treatments. This study provides insight into patients’ perspective and can help guide counseling and treatment selection.

LC-MS based urine untargeted metabolomic analyses to identify and subdivide urothelial cancer.

Urine metabolomics has been a promising technique in the liquid biopsy of urothelial cancer (UC). The comparison of upper tract urothelial cancer (UTUC), lower tract urothelial cancer (BCa), and healthy controls (HCs) need to be performed to find related biomarkers. In our investigation, urine samples from 35 UTUCs, 44 BCas, and 53 gender- and age-matched HCs were analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS). In different groups, the differential metabolites and the disturbed metabolism pathways were explored. Transcriptomics and urine metabolomics are combined to identify the probably disturbed gene in BCa. With an area under the curve (AUC) of 0.815, the panel consisting of prostaglandin I2, 5-methyldeoxycytidine, 2,6-dimethylheptanoyl carnitine, and deoxyinosine was able to discriminate UC from HCs. With an AUC of 0.845, the validation group also demonstrated strong predictive ability. UTUC and BCa without hematuria could be distinguished using the panel of 5'-methylthioadenosine, L-beta-aspartyl-L-serine, dehydroepiandrosterone sulfate, and N'-formylkynurenine (AUC=0.858). The metabolite panel comprising aspartyl-methionine, 7-methylinosine, and alpha-CEHC glucuronide could discriminate UTUC from BCa with hematuria with an AUC of 0.83. Fatty acid biosynthesis, purine metabolism, tryptophan metabolism, pentose and glucuronate interconversions, and arachidonic acid metabolism were dysregulated when comparing UC with HCs. PTGIS and BCHE, the genes related to the metabolism of prostaglandin I2 and myristic acid respectively, were significantly associated with the survival of BCa. Not only could LC-HRMS urine metabolomic investigations distinguish UC from HCs, but they could also identify UTUC from BCa. Additionally, urine metabolomics combined with transcriptomics can find out the potential aberrant genes in the metabolism.

First Comparison of Retroperitoneal Versus Transperitoneal Robot-Assisted Nephroureterectomy with Bladder Cuff: A Single Center Study.

After recent presentation of the first complete robot-assisted retroperitoneal nephroureterectomy with bladder cuff (RRNU) for patients with upper tract urothelial cancer (UTUC), we aimed to compare this new surgical technique with robot-assisted transperitoneal nephroureterectomy (TRNU) representing the current standard of care. Robot-assisted nephroureterectomies (NUs) were retrospectively analyzed and compared based on two groups: transperitoneal versus retroperitoneal approach. Baseline data were collected for patient demographics, tumor characteristics, intra- (EAUiaiC) and postoperative (Clavien-Dindo) complications, and perioperative variables. Tumor characteristics included grade of malignancy, clinical stage, and surgical margin status.Short-term follow-up data including 30-day readmission rates were collected. Statistical analyses were performed assuming a significant p-valueof < 0.05. The analysis includes perioperative patient data after proven UTUC of 24 TRNU versus 12 RRNU (mean age: 70 versus 71 years; BMI: 25.9 versus 26.1 kg/m2; CCI score ≥ 4: 83% versus 75%;ASA score ≥ 3: 37% vs 33%).Intraoperative (16.4% vs 0%, p = 0.35) and postoperative (25% vs 12.5%, p = 0.64) complications demonstrated no significant discrepancy. Notably, RRNU demonstrated significantly shorter surgery time (p < 0.05) and length of stay (p < 0.05). There was no significant difference in histopathological tumor characteristics, whereas significantly more lymph nodes were removed through RRNU (11.0±3.3vs. 6.4±5.1, p < 0.05). Finally, no statistical difference was shown in short-term follow-up. We report the first head-to-head comparison between RRNU and TRNU. RRNU proves to be a safe and feasible approach which appears to be non-inferior to TRNU. RRNU expands the spectrum of minimally invasive treatment options, particularly for patients with major previous abdominal surgery.

Impact of smoking on urologic cancers: a snapshot of current evidence

PurposeThe purpose of this paper is to present evidence regarding the associations between smoking and the following urologic cancers: prostate, bladder, renal, and upper tract urothelial cancer (UTUC).MethodsThis is a narrative review. PubMed was queried for evidence-based analyses and trials regarding the associations between smoking and prostate, bladder, renal, and UTUC tumors from inception to September 1, 2022. Emphasis was placed on articles referenced in national guidelines and protocols.ResultsProstate—multiple studies associate smoking with higher Gleason score, higher tumor stage, and extracapsular invasion. Though smoking has not yet been linked to tumorigenesis, there is evidence that it plays a role in biochemical recurrence and cancer-specific mortality. Bladder—smoking is strongly associated with bladder cancer, likely due to DNA damage from the release of carcinogenic compounds. Additionally, smoking has been linked to increased cancer-specific mortality and higher risk of tumor recurrence. Renal—smoking tobacco has been associated with tumorigenesis, higher tumor grade and stage, poorer mortality rates, and a greater risk of tumor recurrence. UTUC—tumorigenesis has been associated with smoking tobacco. Additionally, more advanced disease, higher stage, lymph node metastases, poorer survival outcomes, and tumor recurrence have been linked to smoking.ConclusionSmoking has been shown to significantly affect most urologic cancers and has been associated with more aggressive disease, poorer outcomes, and tumor recurrence. The role of smoking cessation is still unclear, but appears to provide some protective effect. Urologists have an opportunity to engage in primary prevention by encouraging cessation practices.

VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity in Upper Urinary Tract Urothelial Carcinoma.

Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application.

Abstract 3349: Discovery and validation of methylated DNA markers of upper tract urothelial tract cancers

Abstract Objective: Upper tract urothelial cancers (UTUC) can be difficult to characterize, and non-invasive surveillance tools are lacking. UTUC are often treated with nephroureterectomy (NU). To address these gaps, we sought to discover and validate methylated DNA markers (MDMs) for detection of UTUC. Methods: Archival formalin fixed paraffin embedded (FFPE) tissue samples from NU were pathologically reviewed and punched prior to DNA extraction. Reduced representation bisulfite sequencing (RRBS) was used to identify candidate MDMs that discriminated between UTUC and age-balanced control urothelial tissues (uninvolved ureter/renal pelvic of renal cell carcinoma at radical nephrectomy). Highest ranked (fold-change and p-value) candidate MDMs were biologically validated by quantitative methylation specific PCR in a 2nd independent set of UTUC and age-balanced controls. DNA from healthy donor urine and buffy coat samples was used to assess MDM background signal. Discrimination between UTUC and controls was assessed as the area under the receiver operator characteristic curve (AUC) with corresponding 95% confidence intervals. Results: RRBS assessed 33 UTUC and 26 ureter/renal pelvis controls. 3.01 x 106 CpGs mapped to the reference genome with at least 10X read depth. From 358 candidates, 20 MDMs were selected for biological validation in independent patient samples which included 20 renal pelvis &amp; 16 ureter UTUC and 17 renal pelvis &amp; 15 ureter control specimens. Of UTUC and control patients, 36% and 65% of were men, respectively. Median AUC for comparison of UTUC vs control tissue was 0.87 (IQR 0.81-0.88); AUCs with corresponding 95% CIs are shown for the 10 most accurate MDMs (Table) across all control types. Conclusion: We report discovery and validation of highly sensitive and specific MDMs with potential for accurate non-invasive screening supported by low background in urine and blood. AUCs (95% CI) for selected methylated DNA markers for UTUC vs control tissue, urine, and blood UTUC vs Marker Control Tissue Control Urine Control Buffy C2orf55 0.92 (0.84-1) 0.93 (0.87-1) 0.96 (0.91-1) ANKRD35 0.91 (0.84-0.99) 0.93 (0.86-1) 0.98 (0.94-1) DLX6 0.91 (0.84-0.98) 0.78 (0.66-0.9) 0.97 (0.93-1) Chr8.9998 0.90 (0.82-0.97) 0.91 (0.84-0.97) 0.98 (0.96-1) SP9 0.88 (0.8-0.97) 0.95 (0.9-1) 0.99 (0.98-1) Chr13.1127 0.88 (0.8-0.97) 0.94 (0.89-1) 0.92 (0.85-1) Septin9.r2 0.88 (0.79-0.97) 0.95 (0.88-1) 0.98 (0.94-1) LBX2 0.88 (0.79-0.97) 0.94 (0.88-1) 0.96 (0.91-1) SIM2.r1 0.88 (0.79-0.97) 0.91 (0.82-1) 0.94 (0.86-1) Chr14.1037 0.88 (0.78-0.97) 0.93 (0.85-1) 0.96 (0.9-1) Citation Format: Ojas Bhagra, William R. Taylor, Benjamin R. Gochanour, Patrick H. Foote, Calise K. Berger, Xiaoming Cao, Douglas W. Mahoney, Sara S. Then, Anna M. Gonser, Karen A. Doering, Kelli N. Burger, John C. Cheville, Matthew T. Gettman, John B. Kisiel. Discovery and validation of methylated DNA markers of upper tract urothelial tract cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3349.

Abstract 2421: WST-11 vascular-targeted photodynamic therapy induced immune modulation in upper tract urothelial cancer

Abstract Introduction: Vascular-targeted photodynamic therapy (VTP) with the photosensitizing agent padeliporfin (WST-11/TOOKAD Soluble; STEBA Biotech) has been approved for treating men with low-risk prostate cancer. A phase 1 trial of VTP evaluating treatment of upper tract urothelial carcinoma (UTUC) showed an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option. These results support a recently initiated multi-center Phase 3 trial (ENLIGHTED). Here we conducted a correlative study to assess immune modulatory activities of VTP and its potential association with treatment response. Methods: 19 patients with UTUC received up to two endoscopic VTP treatments in a phase I trial evaluating the safety of VTP. Treatment was applied by endoscopic illumination for 10 minutes at the involved site in the upper tract with three light fluence doses at 100 mW/cm, 150 mW/cm, or 200 mW/cm after intravenous injection of 4 mg/kg WST-11. Complete response was defined by absence of visible tumor and negative urine cytology at 30 days post treatment. To investigate the impact of VTP on the immune system, patient blood samples were collected and banked at 6 time points (base line, 4-6 hrs, 1 day, 1 week, 2 weeks, and 4 weeks post-treatment). Peripheral blood mononuclear cells (PBMCs) were subjected to flow cytometry analyses for T cell activation status and the abundance of myeloid derived suppressive cell (MDSC). Patient analyses were further stratified by complete responders (CR) and partial responders (PR). Mice bearing a murine bladder cell line MB49 or MB49 expressing ovalbumin (MB49-ova) was utilized for the assessment of efficacy and immune modulation by VTP. Results and Conclusions: An increase of the MDSC population in PBMC was observed immediately after VTP treatment (up to 24 hrs) in both CR and PR. However, the MDSC level returned close to pretreatment level in the majority of cases. The frequency of CD8 T cells among the total (CD3 positive) T cells in PBMC was increased immediately after VTP in both CR and PR. However, this increase was more prominent and durable among CR than PR, suggesting an association of treatment response with CD8 T cell driven immune modulation. Analysis of VTP induced antigen-specific immune responses using ovalbumin (ova) tetramers on MB49-ova model showed an increase in ova specific CD8 T cells in the blood and tumor samples at day 7 post VTP, indicating that VTP might induce tumor antigen specific adaptive response. Future analysis will be focused on the analysis of T cell receptor repertoire and immune correlation with clinical benefit. In summary, our pre-clinical and clinical data suggests that VTP induces antigen-specific CD8 T cell responses that may be durable. Citation Format: Kwanghee Kim, Sadna Budhu, Wesley Yip, Andrew Tracey, Andreas Aulitzky, Jasmine Thomas, Karan Nagar, Laura Alvim, Rebecca Dubrovsky, Caoimhe Ryan, Natalia Kudinova, Phillip Wong, Taha Merghoub, Avigdor Scherz, Jonathan Coleman. WST-11 vascular-targeted photodynamic therapy induced immune modulation in upper tract urothelial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2421.

MP69-17 NECESSITY OF PROPHYLACTIC DRAINAGE TUBE IN RETROPERITONEAL LAPAROSCOPIC NEPHROURETERECTOMY WITH OPEN DISTAL URETERECTOMY: A MATCHED-PAIR ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP69-17 NECESSITY OF PROPHYLACTIC DRAINAGE TUBE IN RETROPERITONEAL LAPAROSCOPIC NEPHROURETERECTOMY WITH OPEN DISTAL URETERECTOMY: A MATCHED-PAIR ANALYSIS Hiroki Hagimoto, Mutsushi Kawakita, and Toshinari Yamasaki Hiroki HagimotoHiroki Hagimoto More articles by this author , Mutsushi KawakitaMutsushi Kawakita More articles by this author , and Toshinari YamasakiToshinari Yamasaki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To assess the necessity of prophylactic drain placement in retroperitoneal laparoscopic nephroureterectomy with open distal ureterectomy for upper tract urothelial cancer. METHODS: Between July 2011 and March 2021, 200 patients with localized clinical Tis-T3 upper urinary tract urothelial carcinoma underwent laparoscopic nephroureterectomy with open distal ureterectomy. After removing the specimen, drainage tubes were placed on the renal beds and/or in the retrovesical spaces. Drain tubes were omitted for most patients after 2017. We compared the postoperative outcomes between the patients with drain placement (D+ group) and without drain placement (D- group) by propensity score matching. RESULTS: A total of 164 patients (90 in the D+ group and 74 in the D- group) were enrolled, and matched pairs of 108 patients were analyzed. There was no significant difference in the incidence of complications according to Clavien–Dindo grade in the two groups after the propensity score matching. There was no significant difference in the incidence of postoperative lymphocele (n=5 vs. 9, p=0.395) and symptomatic lymphocele (n=1 vs. 1, p=1) between the two groups. The length of hospital stay was significantly shorter in the D- group (11 vs. 8 days, p<0.0001). CONCLUSIONS: Omitting the drainage tube after laparoscopic radical nephroureterectomy does not increase postoperative complications or lymphocele and shortens the post-hospital stay. Source of Funding: No funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e971 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroki Hagimoto More articles by this author Mutsushi Kawakita More articles by this author Toshinari Yamasaki More articles by this author Expand All Advertisement PDF downloadLoading ...

MP47-04 HYPERTENSION IS ASSOCIATED WITH WORSENED ONCOLOGICAL SURVIVAL OUTCOMES IN PATIENTS UNDERGOING NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA: ANALYSIS OF THE ROBUUST REGISTRY

MP47-04 HYPERTENSION IS ASSOCIATED WITH WORSENED ONCOLOGICAL SURVIVAL OUTCOMES IN PATIENTS UNDERGOING NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA: ANALYSIS OF THE ROBUUST REGISTRY

MP75-10 SURVIVAL OUTCOMES BY RACE FOLLOWING MINIMALLY INVASIVE SURGICAL TREATMENT FOR UPPER TRACT UROTHELIAL CARCINOMA: AN ANALYSIS OF THE ROBUUST REGISTRY

MP75-10 SURVIVAL OUTCOMES BY RACE FOLLOWING MINIMALLY INVASIVE SURGICAL TREATMENT FOR UPPER TRACT UROTHELIAL CARCINOMA: AN ANALYSIS OF THE ROBUUST REGISTRY