20-Gene Prognostic Test for Bladder Cancer Developed
Tool identifies patients with a high likelihood of lymph node involvement before surgery.!--h2>
Scientists report that they have designed a molecular test to predict which bladder cancer patients may have cancer involvement in their lymph nodes at the time of surgery. The test analyzes 20 genes on tumor biopsies.
The study was published online January 20 in The Lancet Oncology and is titled “A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment.”
Since the most important predictor of recurrence after cystectomy is pathologically positive nodes, the researchers’ aim was to assess techniques that define this stage for the selection of patients for neoadjuvant chemotherapy. They developed a gene-expression model (GEM) to predict the pathological node status in primary tumor tissue from three independent cohorts of patients who were clinically node negative. Tumor samples were collect from patients in Canada, Germany, and the U.S.
From a subset of transcripts detected by microarrays from paired frozen and formalin-fixed tissues (32 pairs), the team developed the GEM and cutoffs that identified patient strata with raised risk of nodal involvement by use of two separate training cohorts (90 and 66 patients). They then assessed the GEM and cutoffs to predict node-positive disease in tissues from a Phase III trial cohort of 185 patients.
Using this information the scientists created a 20-gene GEM with an area under the curve of 0.67 for prediction of nodal disease at surgery. The cutoff system identified patients with high relative risk and low relative risk of node-positive disease. Multivariate logistic regression showed the GEM predictor was independent of age, sex, pathological stage, and lymphovascular space invasion.
“Randomized clinical trials have shown that giving neo-adjuvant chemotherapy extends patient lives, but only 5 to 15 percent of patients benefit,” points out urologic surgeon Dan Theodorescu, M.D., Ph.D., director of the University of Colorado Cancer Center and lead author of the study. “Patients who have cancer in the lymph nodes at time of diagnosis are likely to benefit the most.
“Today, only about 2 percent of people with invasive bladder cancer have presurgical chemotherapy, because it’s quite difficult to get through, and there is fear of delaying surgery,” Dr. Theodorescu continues. “We need a better way to predict who will benefit, and that’s what this test does by identifying patients with a high likelihood of lymph node involvement before surgery.”