title: A 20 gene model for predicting nodal involvement in bladder cancer patients with muscle invasive tumors.
abstract: Bladder cancer is the fourth most common cancer in males worldwide and also the most expensive cancer to treat. Approximately 25% of patients with muscle invasive disease are found to harbor occult lymph node involvement at the time of cystectomy and this finding is associated with a 5-year survival rate of <30%. If these patients could be identified pre-operatively, use of neoadjuvant chemotherapy may be advantageous because this approach has been shown to confer a small survival advantage in patients with muscle invasive disease. However, because only a few patients benefit from this approach it has not been used extensively in the United States with fewer than 2% of patients undergoing this treatment. This is largely due to concerns that since neoadjuvant therapy is beneficial for only a few patients, it has the potential to delay surgery in the majority who do not benefit. However, since neoadjuvant therapy is most likely to benefit those patients at highest risk for progression of disease, it follows that patients with lymph node metastases would constitute an ideal group for such treatment. Hence, if patients with occult node involvement prior to cystectomy could be identified, they would constitute an ideal group for application of neoadjuvant therapy as they are most likely to benefit. In this summary, we describe the first multi-analyte gene expression model developed for predicting occult nodal involvement at cystectomy in bladder cancer patients, for the purpose of making better informed decisions regarding neoadjuvant therapy. The 20 gene model, which was developed on Affymetrix Human Genome U133A and U133 Plus 2.0 arrays, identified individuals with high relative risk (RR) of nodal involvement (RR = 1.74, 95% CI, 1.03 - 2.93) intermediate risk (RR = 1.05, 95% CI, .45 - 2.41), and low risk (RR = 0.74, 95% CI, 0.51 - 0.96), when evaluated in an independent test dataset. The 20 gene model can be applied to formalin-fixed paraffin embedded tissue with sufficient tumor content, making implementation in routine diagnostic tissue highly feasible. Although a clinical assay for the gene panel has not undergone analytic validation in a clinical laboratory setting, multiple platforms are available which could be utilized for routine testing, including real-time reverse transcriptase PCR directed against individual analytes as well as microarray approaches.
authors.affiliation: Department of Surgery, University of Colorado, Aurora, Colorado, USA; Department of Pathology, University of Colorado, Aurora, Colorado, USA; University of Colorado Cancer Center and The Public Library of Science (PLoS) is a non-profit open-access publisher, committed to making scientific and medical research literature a freely accessible public resource.
authors.forename: Garrett
authors.initials: G
authors.lastname: Dancik
authors.forename: Dara
authors.initials: D
authors.lastname: Aisner
authors.forename: Dan
authors.initials: D
authors.lastname: Theodorescu