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Histological variant as the significant predictor of survival in patients with lymph node positive urothelial carcinoma of the bladder.

ABSTRACT: The aim of this study was to evaluate the impact of histological variants of urothelial carcinoma (UC) on survival outcomes in patients with lymph node (LN) positive UC of the bladder. We reviewed and analyzed the clinical data from 424 patients who underwent radical cystectomy (RC) with pelvic lymph node dissection (PLND) for UC of the bladder and who did not receive neoadjuvant chemotherapy in our institution between 1991 and 2012. In total, 92 patients (21.7%) had histologically confirmed LN positive disease. In the LN negative group (332 patients), histological variants of UC were not a significant predictor in univariate analysis. However, in the LN positive group, histological variants of UC were a significant independent prognostic factor of overall survival (hazard ratio (HR) 3.54; 95% confidence interval (CI) 1.77-7.08, p < 0.001) and cancer specific survival (HR 3.66; 95% CI 1.69-7.90, p = 0.001) in both uni-variate and multivariate Cox regression analyses. The presence of histological variants of UC may indicate a worse prognosis in LN positive patients after RC with PLND for UC of the bladder and more aggressive adjuvant therapy may be required for the improvement of postoperative survival.

SUBMITTER: Kim HS

PROVIDER: S-EPMC4427059 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Histological variant as the significant predictor of survival in patients with lymph node positive urothelial carcinoma of the bladder.

Kim Hyung Suk HS Moon Kyung Chul KC Jeong Chang Wook CW Kwak Cheol C Kim Hyeon Hoe HH Ku Ja Hyeon JH

Scientific reports 20150511

The aim of this study was to evaluate the impact of histological variants of urothelial carcinoma (UC) on survival outcomes in patients with lymph node (LN) positive UC of the bladder. We reviewed and analyzed the clinical data from 424 patients who underwent radical cystectomy (RC) with pelvic lymph node dissection (PLND) for UC of the bladder and who did not receive neoadjuvant chemotherapy in our institution between 1991 and 2012. In total, 92 patients (21.7%) had histologically confirmed LN ...[more]

PMID: 25959144

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Project description:The status of lymph node (LN) metastases plays a decisive role in the selection of surgical procedures and post-operative treatment. Several histopathologic features, known as predictors of LN metastasis, are commonly available post-operatively. Medical imaging improved pre-operative diagnosis, but the results are not fully satisfactory due to substantial false positives. Thus, a reliable and robust method for pre-operative assessment of LN status is urgently required. We developed a prediction model in a training set from the TCGA-BLCA cohort including 196 bladder urothelial carcinoma samples with confirmed LN metastasis status. Least absolute shrinkage and selection operator (LASSO) regression was harnessed for dimension reduction, feature selection, and LNM signature building. Multivariable logistic regression was used to develop the prognostic model, incorporating the LNM signature, and a genomic mutation of MLL2, and was presented with a LNM nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was evaluated by the testing set from the TCGA cohort and independent validation was assessed by two independent cohorts. The LNM signature, which consisted of 48 selected features, was significantly associated with LN status (p < 0.005 for both the training and testing sets of the TCGA cohort). Predictors contained in the individualized prediction nomogram included the LNM signature and MLL2 mutation status. The model demonstrated good discrimination, with an area under the curve (AUC) of 98.7% (85.3% for testing set) and good calibration with p = 0.973 (0.485 for testing set) in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis demonstrated that the LNM nomogram was clinically useful. This study presents a pre-operative nomogram incorporating a LNM signature and a genomic mutation, which can be conveniently utilized to facilitate pre-operative individualized prediction of LN metastasis in patients with bladder urothelial carcinoma.

Project description:BackgroundThe effect of gender on the prognosis of bladder cancer (BCa) in different metastatic sites is insufficiently understood. We aimed to assess the impact and potential mechanisms of a combination of gender dimorphism and BCa metastasis sites on the risk of death.MethodsIndependent predictors of overall survival and cancer-specific survival were analyzed after stratification by gender and metastasis sites from the Surveillance, Epidemiology, and End Results database. Furthermore, gender-differentially expressed genes (DEGs) and function-enriched annotations for patients with lymph node metastasis (LNM) were identified from The Cancer Genome Atlas (TCGA) database. A gender-associated signature was constructed in TCGA and validated in the IMvigor210 trial, and the magnetic resonance imaging-based radiomics signature was developed in our center to predict the gender-associated signature.ResultsIn patients with metastatic BCa, the most common site of metastasis is bone in men and lung in women. Moreover, stratified by sex, LNM had a better prognosis in men than visceral metastasis, which was not observed in female. Similarly, stratified by the metastasis site, the prognosis of men in patients with LNM is better than that of women, which was not observed in visceral metastasis patients. Enrichment of DEGs between sexes in patients with LNM may be related to metastasis and tumor immunity, especially the role of neutrophils. Moreover, the gender-associated signature is related to the clinicopathological characteristics of patients, and patients in the high-risk group had worse survival outcomes, and higher susceptibility to cisplatin, docetaxel, camptothecin, and paclitaxel. A nomogram combined with the signature and clinical staging showed significant predictive power in survival prediction. Furthermore, patients with high radiomics scores had a strong tendency for high-risk group.ConclusionThese results may improve the understanding of the differences in tumor biology between sexes and thus provide additional evidence for individualized treatment in BCa.

Project description:Contemporary treatment of node-positive (N+) colon cancer consists of adjuvant chemotherapy; however, randomized data supporting this practice were derived from lesions T2 or greater. Minimal data exist regarding the use and need for adjuvant chemotherapy in T1N+ disease.The aim of this study was to determine treatment trends and the effects of adjuvant chemotherapy on T1N+ colon cancers by using the National Cancer Database.This was a retrospective study. Baseline demographics, tumor, and cancer treatment characteristics were compared. Groups were matched on the propensity to receive chemotherapy. Adjusted long-term survival stratified by chemotherapy use was compared by using the Kaplan-Meier method with the log-rank test. Predictors of not receiving chemotherapy were identified by using a multivariable logistic regression model.Data were collected from the National Cancer Database, which collects cancer data from over 1500 cancer centers.We identified patients from 1998 to 2006 with T1N+ disease, excluding those with metastatic disease or previous cancer. Patients were stratified based on whether or not they received chemotherapy.The primary outcome measure of this study was long-term survival.Three thousand one hundred thirty-seven patients had T1N+ disease; 70.6% (n = 2216) received chemotherapy, and utilization significantly increased from 1998 to 2011 (p < 0.001). Unadjusted analysis revealed that patients treated with chemotherapy were statistically younger and healthier, and had shorter postoperative lengths of stay (all p < 0.001). Unadjusted 5-year survival was higher in patients receiving chemotherapy (87.9% vs 63.0% in patients with no chemotherapy; p < 0.001) and this persisted after propensity matching with (83.4% and 63.0% in patients with or without chemotherapy; p < 0.001). Only age (OR, 0.29; p < 0.001) predicted not receiving chemotherapy.Limitations include potential selection bias as well as the inability to compare disease-free survival/recurrence.Adjuvant chemotherapy appears to significantly improve long-term survival in patients receiving chemotherapy in T1N+ disease. Thus, the use of chemotherapy in T1N+ disease is justified and provides a highly significant survival benefit.

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Histological variant as the significant predictor of survival in patients with lymph node positive urothelial carcinoma of the bladder.

Publications

Histological variant as the significant predictor of survival in patients with lymph node positive urothelial carcinoma of the bladder.

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