Evidence map›Paper›PMID 25344601›Full record

ArticleJournal of the National Cancer Institute2014

Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer.

Anirban P Mitra, Lucia L Lam, Mercedeh Ghadessi, Nicholas Erho, Ismael A Vergara, Mohammed Alshalalfa, Christine Buerki, Zaid Haddad, Thomas Sierocinski, Timothy J Triche and 4 more

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed.

  1. Review
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  7. [Molecular tumor board-urothelial cancer].Der Urologe. Ausg. A · 2019
    Review
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  13. Review
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  18. Understanding the molecular pathogenesis and prognostics of bladder cancer: an overview.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2016
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Anirban P MitraDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB). apmitra@gmail.com.
Lucia L LamDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Mercedeh GhadessiDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Nicholas ErhoDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Ismael A VergaraDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Mohammed AlshalalfaDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Christine BuerkiDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Zaid HaddadDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Thomas SierocinskiDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Timothy J TricheDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Eila C SkinnerDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Elai DavicioniDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Siamak DaneshmandDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).
Peter C BlackDepartment of Pathology and Center for Personalized Medicine (APM, TJT) and Institute of Urology and Norris Comprehensive Cancer Center (SD), University of Southern California, Los Angeles, CA; GenomeDx Biosciences, Inc., Vancouver, BC (LLL, MG, NE, IAV, MA, CB, ZH, TS, TJT, ED); Department of Urology and the Stanford Cancer Institute, Stanford University, Stanford, CA (ECS); Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada (PCB).

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone.

methodsTranscriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. Genomic (GC) and clinical (CC) classifiers for predicting recurrence were developed on a discovery set (n = 133). Performances of GC, CC, an independent clinical nomogram (IBCNC), and genomic-clinicopathologic classifiers (G-CC, G-IBCNC) were assessed in the discovery and independent validation (n = 66) sets. GC was further validated on four external datasets (n = 341). Discrimination and prognostic abilities of classifiers were compared using area under receiver-operating characteristic curves (AUCs). All statistical tests were two-sided.

resultsA 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. This was higher than individual clinical variables, IBCNC (AUC = 0.73), and comparable to CC (AUC = 0.78). Performance was improved upon combining GC with clinical nomograms (G-IBCNC, AUC = 0.82; G-CC, AUC = 0.86). G-CC high-risk patients had elevated recurrence probabilities (P < .001), with GC being the best predictor by multivariable analysis (P = .005). Genomic-clinicopathologic classifiers outperformed clinical nomograms by decision curve and reclassification analyses. GC performed the best in validation compared with seven prior signatures. GC markers remained prognostic across four independent datasets.

conclusionsThe validated genomic-based classifiers outperform clinical models for predicting postcystectomy bladder cancer recurrence. This may be used to better identify patients who need more aggressive management.

Indexed as

CystectomyGene Expression Regulation, NeoplasticTranscriptomeAdultAgedArea Under CurveFemaleHumansKaplan-Meier EstimateLymphatic MetastasisMaleMiddle AgedNeoplasm InvasivenessNeoplasm Recurrence, LocalNomogramsPredictive Value of TestsRNA, Neoplasm

Identifiers

PMID25344601
PMCPMC4241889

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.