Perioperative systemic chemo‐immunotherapy for upper urinary tract urothelial carcinoma
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ABSTRACT:
SUBMITTER: Hwang E
PROVIDER: S-EPMC7161362 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:TP53 mutation patterns are associated with prognosis of various cancers. This study was designed to investigate the association between TP53 mutation patterns and recurrence patterns in upper urinary tract urothelial carcinoma (UTUC) patients. A total of 165 consecutive UTUC patients who underwent nephroureterectomies were enrolled for measuring mutation patterns of TP53 gene from exome 2 to 11. Bladder recurrence, contralateral UTUC recurrence, and metastases were compared among groups by using log-rank test and Cox proportional hazard model. Single base substitution as an A:T to T:A transversion was noted in 55 (33.3%) patients (AT group). Forty-two (25.5%) patients had TP53 mutations with only other than A:T to T:A transversion (NAT group), and 68 patients (41.2%) had wide-type TP53 (WT group). AT group was predominately female (64%, 52%, 29%, respectively), had a higher incidence of end-stage renal disease (24%, 14%, 10%, respectively), and had more high-grade tumors (82%, 74%, 62%, respectively) compared to NAT and WT groups. With adjustment of tumor grade/stages, bladder and contralateral UTUC recurrence-free survival duration was shortest in NAT (p < 0.001) and AT group (p < 0.001), respectively. NAT group had a shorter metastasis-free survival duration than the other two groups combined (p = 0.018). As a result, A:T to T:A transversion increased contralateral UTUC recurrence risk, but other mutations in TP53 raised the hazard of bladder recurrence and metastases. Therefore, TP53 mutation pattern may be a useful biomarker to predict recurrence patterns of UTUC patients.
| S-EPMC5216718 | biostudies-literature
Project description:DNA sequencing of 9 Taiwanese patients with upper-urinary tract urothelial cell carcinoma who are suspected of exposure to aristolochic acid
| PRJEB4138 | ENA
Project description:The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities.
| S-EPMC7821318 | biostudies-literature
Project description:PURPOSE:A better understanding of the molecular basis of urothelial carcinoma (UC) is needed to refine the clinical decision-making process. METHODS AND MATERIALS:We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs) were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC) and urinary bladder UC (UBUC) were compared. RESULTS:Tumor samples from 31 UTUC and 61 UBUC patients were included in analysis. The two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was longer in UTUC than UBUC patients, though this was statistically nonsignificant (59 vs 41 months, P=.137). In total, we found 982 genetic alterations from 92 samples: single nucleotide variants were the most common type of somatic mutation (479/508, 94.3%). Frequently detected somatic mutations included TP53 (68.5%), KDR (41.3%), and PIK3CA (17.4%). Notably, RB1 mutations were the only mutations significantly different between the UBUC and UTUC groups (19.7% vs. 0%, P=.020). The most common types of CNVs included amplifications (56/62, 90.3%): 17.7% of patients identified amplifications in NOTCH1. We also identified five translocations in the entire study population, including one case with FGFR3-TACC3 (Chr4) fusion. CONCLUSION:Within a small study population, we identified similar genetic alterations in both UTUC and UBUC patients, indicating a basis for similar management strategies.
| S-EPMC5699894 | biostudies-literature
Project description:Signal transducer and activator of transcription 3 (STAT3) plays a prominent role in the growth and invasion of several types of solid tumors. In this study, to assess the expression status and prognostic significance of the STAT3 pathway in upper urinary tract urothelial carcinoma (UTUC), we immunohistochemically stained for STAT3 and STAT3 pathway proteins, sphingosine-1-phosphate receptor 1 (S1PR1) and interleukin-6 (IL-6), in a tissue microarray containing 99 UTUC specimens. There were no significant associations between STAT3, S1PR1, or IL-6 expression pattern and tumor grade or pT stage. However, the patients with high STAT3 tumor had a significantly higher risk of both disease progression (p = 0.009) and cancer-specific mortality (p = 0.009), but not with tumors expressing S1PR1 or IL-6. High STAT3 expression in the nucleus was also associated with a significantly higher risk of both disease progression (p = 0.003) and cancer-specific mortality (p = 0.034). Multivariate analysis revealed that high STAT3 expression in the nucleus was significantly associated with cancer-specific survival after adjustment for pathological stage, lymph node involvement, lymphovascular invasion, and tumor grade (HR = 2.136, 95% CI = 1.009-4.767, p = 0.047). Our findings indicated that STAT3 could be a cancer-promoting factor and potentially a significant prognostic factor in UTUC.
| S-EPMC6084864 | biostudies-literature
Project description:Though radical nephroureterectomy remains the gold standard treatment for high grade or invasive disease in upper tract urothelial cancer (UTUC), kidney-sparing surgery has become preferred for low risk disease, in order to minimize morbidity and preserve renal function. Many methods exist for endoscopic management, whether via an antegrade percutaneous or retrograde ureteroscopic approach, including electroresection, laser ablation, and fulguration. There has been an increase in use of adjuvant intracavitary therapy, predominantly using mitomycin and bacillus Calmette-Guerin (BCG), to reduce recurrence after primary endoscopic management for noninvasive tumors, although efficacy remains questionable. Intraluminal BCG has additionally been used for primary treatment of CIS in the upper tract, with around 50% success. Newer investigations include use of narrow band imaging or photodynamic diagnosis with ureteroscopy to improve visualization during diagnosis and treatment. Genomic characterization may improve selection for kidney-sparing surgery as well as identify actionable mutations for systemic therapy. The evolution in adjuvant management has seen strategies to increase the dwell time and the urothelial contact of intraluminal agents. Lastly, chemoablation using a hydrogel for sustained effect of mitomycin is under investigation with promising early results. Continued expansion of the armamentarium available and better identification and characterization of tumors ideal for organ-sparing treatment will further improve kidney preservation in UTUC.
| S-EPMC7475682 | biostudies-literature
Project description:Metastatic upper urinary tract urothelial carcinoma (mUTUC) is a relatively rare urothelial carcinoma, and little attention has been given to it. Our study established a nomogram by analyzing the prognostic factors of mUTUC to predict the survival of patients and revealed that the role of surgery at the primary tumor site. We extracted our data (2010-2016) from the Surveillance, Epidemiology, and End Results (SEER) database, and 628 patients with distant metastasis were identified. Propensity score matching (PSM) was used to balance the clinical variable bias in a 1:1 ratio. After PSM, we enrolled 502 patients in our study cohort. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves showed that T stage, N stage, hepatic metastasis, surgery, and chemotherapy were prognostic factors for mUTUC before and after PSM. Based on the findings, a nomogram was constructed to predict the 12-month survival of patients with distant metastasis. The analysis of subgroups of T stage, N stage, and different metastatic sites demonstrated that the survival of patients with T1/T2, N0/N1/N2/N3, metastasis including liver, and metastasis including bone could be improved by a combination of surgery and chemotherapy, while for the patients with T3/T4/TX, NX, metastasis including lung, and metastasis including distant lymph nodes, chemotherapy alone was a better choice to improve their overall survival. Radiotherapy has been proven to be useful for patients with N1/N2/N3 stage. We have provided more precise treatment strategies for stage IV patients. Our research fully affirms the role of surgery on primary site in UTUC patients with distant metastasis and the significance of classifying the patients into subgroups by integrating variables including T stage, N stage, and different metastatic sites to select the optimal treatment method.
| S-EPMC8607251 | biostudies-literature
Project description:Genome-wide methylation analysis of upper urinary tract urothelial carcinoma using Infinium MethylationEPIC BeadChip Kit
| EGAD00010002096 | EGA
Project description:ObjectiveTo assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery.Patients and methodsData from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses.ResultsA pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS.ConclusionsOur present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.
| S-EPMC8246716 | biostudies-literature
Project description:Late pulmonary metastasis from urothelial carcinoma (UC) of the upper urinary tract is extremely rare.A 76-year-old man was referred to our hospital due to an abnormal shadow on chest X-ray. He had a history of left nephrectomy with a diagnosis of UC in the renal pelvis 29 years previously. Computed tomography showed a mass lesion in the right middle lobe of the lung that measured 4.9 cm in diameter. A transbronchial biopsy revealed the tumor to be metastatic pulmonary UC, and he underwent right middle lobectomy of the lung.Long-term postoperative follow-up of patients with UC might be necessary after radical nephrectomy.
| S-EPMC5285295 | biostudies-literature