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Extranodal Extension Predicts Poor Survival Outcomes among Patients with Bladder Cancer.

ABSTRACT: Several lymph node-related prognosticators were reported in bladder cancer patients with lymph node involvement and receiving radical cystectomy. However, extranodal extension (ENE) remained a debate to predict outcomes. A retrospective analysis of 1303 bladder cancer patients receiving radical cystectomy and bilateral pelvic lymph node dissection were identified in the National Taiwan Cancer Registry database from 2011 to 2017. Based on the 304 patients with lymph node involvement, the presence of ENE and major clinical information were recorded and calculated. The overall survival (OS) and cancer-specific survival (CSS) were estimated with Kaplan-Meier analysis and compared using the log-rank test. Hazard ratios (HR) and the associated 95% confidence intervals were calculated in the univariate and stepwise multivariable models. In the multivariable analysis, ENE significantly reduced OS (HR = 1.74, 95% CI 1.09-2.78) and CSS (HR = 1.69, 95% CI 1.01-2.83) more than non-ENE. In contrast, adjuvant chemotherapy was significantly associated with better OS and CSS upon the identification of pathological nodal disease. Reduced OS and CSS outcomes were observed in the pathological nodal bladder cancer patients with ENE compared with those without ENE. After the identification of pathological nodal disease, adjuvant chemotherapy was associated with better survival outcomes.

SUBMITTER: Liao YA

PROVIDER: S-EPMC8391350 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Extranodal Extension Predicts Poor Survival Outcomes among Patients with Bladder Cancer.

Liao Yi-An YA Chiang Chun-Ju CJ Lee Wen-Chung WC Zhuang Bo-Zhi BZ Chen Chung-Hsin CH Pu Yeong-Shiau YS

Cancers 20210815 16

<h4>Background</h4>Several lymph node-related prognosticators were reported in bladder cancer patients with lymph node involvement and receiving radical cystectomy. However, extranodal extension (ENE) remained a debate to predict outcomes.<h4>Methods</h4>A retrospective analysis of 1303 bladder cancer patients receiving radical cystectomy and bilateral pelvic lymph node dissection were identified in the National Taiwan Cancer Registry database from 2011 to 2017. Based on the 304 patients with ly ...[more]

PMID: 34439261

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Project description:Objectives: Despite the inclusion of extranodal extension (ENE) in the recent staging system, the presence of ENE alone is not sufficient to depict all clinical situations, as ENE is frequently found in multiple nodes. Thus, the purpose of this study was to evaluate the surgery-based treatment outcomes and clinicopathological features of oral cavity squamous cell carcinoma (OCSCC) patients with ENE found in bilateral multiple cervical metastases. Materials and methods: A retrospective single-institutional study of OCSCC patients with bilateral ENE nodes was performed from January 2011 to December 2018. OCSCC patients of different admission statuses (with primary lesions (PL), recurrent lesions (RL) and isolated neck metastases (INM)) were included for subgroup comparisons. All patients received surgical treatment with/without adjuvant therapies and had complete follow-up data. Disease-free survival (DFS) was regarded as the main outcome. Time-to-relapse data were also collected for comparison. Results: A total of 128 patients were included, of whom 97 (75.8%) were male. The mean follow-up period reached 15 months. Among the patients, 85 (66.4%) were treated for PLs, followed by 26 (20.3%) treated for RLs after failed prior therapy and 17 (13.3%) treated for INMs (concurrent or sequential). The DFS rate was merely 35.2%. Treatment-related factors such as surgical margin (p=0.003), postoperative adjuvant therapy (p=0.014) and perioperative complications (p=0.036) were significantly associated with patient outcomes. In addition, oral lesion-related variables such as oral subsites (p=0.037), T classification (p=0.026) and skull base involvement (p=0.040) were indicators of a worse prognosis. For bilateral ENE features, ENE subclassification (p=0.036), maximum size of ENE nodes (p=0.039) and arterial nodal encasement (p=0.025) tended to predict the surgery-based treatment outcomes of these patients. Conclusions: Bilateral cervical metastases with ENE features, though uncommon, are a serious regional burden, and these patients have lower-than-expected treatment outcomes, especially those with RLs or INMs. A fairly large number of OCSCC patients with advanced oral lesions gain little benefit from intensified salvage surgical treatment. Such treatment should instead be offered to select patients with smaller bilateral ENE nodes (<3 cm) and those with lower ENE subclassifications and no arterial nodal encasement.

Project description:BackgroundThe fatality and recurrence rates of bladder cancer (BC) have progressively increased. DNA methylation is an influential regulator associated with gene transcription in the pathogenesis of BC. We describe a comprehensive epigenetic study performed to analyse DNA methylation-driven genes in BC.MethodsData related to DNA methylation, the gene transcriptome and survival in BC were downloaded from The Cancer Genome Atlas (TCGA). MethylMix was used to detect BC-specific hyper-/hypo-methylated genes. Metascape was used to carry out gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A least absolute shrinkage and selection operator (LASSO)-penalized Cox regression was conducted to identify the characteristic dimension decrease and distinguish prognosis-related methylation-driven genes. Subsequently, we developed a six-gene risk evaluation model and a novel prognosis-related nomogram to predict overall survival (OS). A survival analysis was carried out to explore the individual prognostic significance of the six genes.ResultsIn total, 167 methylation-driven genes were identified. Based on the LASSO Cox regression, six genes, i.e., ARHGDIB, LINC00526, IDH2, ARL14, GSTM2, and LURAP1, were selected for the development of a risk evaluation model. The Kaplan-Meier curve indicated that patients in the low-risk group had considerably better OS (P = 1.679e-05). The area under the curve (AUC) of this model was 0.698 at 3 years of OS. The verification performed in subgroups demonstrated the validity of the model. Then, we designed an OS-associated nomogram that included the risk score and clinical factors. The concordance index of the nomogram was 0.694. The methylation levels of IDH2 and ARL14 were appreciably related to the survival results. In addition, the methylation and gene expression-matched survival analysis revealed that ARHGDIB and ARL14 could be used as independent prognostic indicators. Among the six genes, 6 methylation sites in ARHGDIB, 3 in GSTM2, 1 in ARL14, 2 in LINC00526 and 2 in LURAP1 were meaningfully associated with BC prognosis. In addition, several abnormal methylated sites were identified as linked to gene expression.ConclusionWe discovered differential methylation in BC patients with better and worse survival and provided a risk evaluation model by merging six gene markers with clinical characteristics.

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Extranodal Extension Predicts Poor Survival Outcomes among Patients with Bladder Cancer.

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Extranodal Extension Predicts Poor Survival Outcomes among Patients with Bladder Cancer.

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