Dataset Information

A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable.

ABSTRACT:

Background

Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that predicted lymph node-positive disease at radical cystectomy in clinically node-negative MIBC patients, which would be a justification for upfront chemotherapy.

Methods

We studied diagnostic transurethral resection of bladder tumors (dTURBT) of 150 MIBC patients (urothelial carcinoma) who were subsequently treated by radical cystectomy and pelvic lymph node dissection. RNA was isolated and the expression level of the 20 genes was determined on a qRT-PCR platform. Normalized Ct values were used to calculate a risk score to predict the presence of node-positive disease. The Cancer Genome Atlas (TCGA) RNA expression data was analyzed to subsequently validate the results.

Results

In a univariate regression analysis, none of the 20 genes significantly correlated with node-positive disease. The area under the curve of the risk score calculated by the 20-gene expression signature was 0.54 (95% Confidence Interval: 0.44-0.65) versus 0.67 for the model published by Smith et al. Node-negative patients had a significantly lower tumor grade at TURBT (p = 0.03), a lower pT stage (p<0.01) and less frequent lymphovascular invasion (13% versus 38%, p<0.01) at radical cystectomy than node-positive patients. In addition, in the TCGA data, none of the 20 genes was differentially expressed in node-negative versus node-positive patients.

Conclusions

We conclude that a 20-gene expression signature developed for nodal staging of MIBC at radical cystectomy could not be validated on a qRT-PCR platform in a large cohort of dTURBT specimens.

SUBMITTER: van Kessel KE

PROVIDER: S-EPMC5358850 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable.

van Kessel Kim E M KE van de Werken Harmen J G HJ Lurkin Irene I Ziel-van der Made Angelique C J AC Zwarthoff Ellen C EC Boormans Joost L JL

PloS one 20170320 3

<h4>Background</h4>Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that ...[more]

PMID: 28319171

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Project description:The number of lymph node dissections (LNDs) is an independent factor influencing the survival time of patients with bladder cancer (BCa) after radical resection (RC). The present study aimed to investigate the association between the number of LNDs and the survival of patients with BCa at different stages and who underwent RC in the United States of America and China. Records from 17,730 American patients with BCa and 158 Chinese patients with BCa were collected from the Surveillance, Epidemiology and End Results (SEER) and the Shanghai Tenth People's Hospital (China) databases, respectively. Kaplan-Meier curve and χ2 test were used to determine the overall survival time (OS) of patients with BCa. Cox regression analysis was used to analyze the effects of LND number on OS. Overall, 13,421 (75.7%) patients were negative for lymph node metastasis (N0) and 4,309 (24.3%) were positive for lymph node metastasis (N+) among the 17,730 American patients with BCa. In the group of 158 Chinese patients, 125 (79.1%) were N0 and 33 (20.9%) were N+. In the American patients, the median number of dissected nodes was 11.0 [interquartile range (IQR)=3.0-21.0] for N0 patients and 14.0 (IQR=8.0-23.0) for N+ patients. The median number of LNDs was 5.0 (IQR=2.0-7.0) for Chinese N0 patients and 5.0 (IQR=1.5-10.5) for Chinese N+ patients. The number of LNDs may therefore be an independent factor associated with survival in patients who underwent RC. Furthermore, a higher number of LNDs was associated with longer OS in patients with BCa [American patients, ≥13 nodes vs. ≤5 nodes, hazard ratio (HR)=0.62, 95% confidence interval (CI)=0.59-0.65, P<0.001; Chinese patients, ≥5 nodes vs. ≤1 node, HR=0.27, 95% CI=0.12-0.62, P=0.002]. The number of LNDs in patients with BCa and N+ was higher compared with number of LNDs in patients with BCa and N0 who underwent RC. More extensive LND improved the OS in both the patients from USA and China. Increasing the number of LNDs may therefore be crucial when treating patients with BCa.

Dataset Information

A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable.

Background

Methods

Results

Conclusions

Publications

A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable.

Similar Datasets

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