There is substantial heterogeneity in treatment response he said. “Empirical medicine” has led to “stratified medicine” to improve prediction based on population characteristics - and now the new age will bring individual, “personalized medicine.” Molecular understanding of disease drives development of biomarkers of which there are 3 categories; predisposition markers (assessed in people without cancers and used to assess risk), prognostic markers (will give information about the cancer’s aggressiveness, risk, etc), and predictive markers (informative about response to therapy). Both the host and tumor need to be tested. A molecular blueprint is obtained of the host and tumor to identify prognostic and predictive markers. In bladder cancer, the major challenges are improving primary diagnosis, optimizing surveillance of non-muscle invasive disease, and to reduce mortality of muscle invasive disease.
Regarding predisposition markers, genome-wide association studies (GWAS) identify polymorphisms, small variations at single nucleotide sites. GWAS have identified small nucleotide polymorphisms that differ in bladder cancer compared to controls. This genetic risk can be combined with environmental risks in nomograms. Molecular genetics of bladder cancer stratify patients with FGFR3 mutations that occur in most non-muscle invasive cancers. Paradoxically, patients with this mutation had improved prognosis. In recurrent tumors, the mutation is still present in 52%, suggesting this technology can be used for followup. P53 alterations are more pronounced in muscle invasive bladder cancer and can similarly be targeted.
He described a 20-gene biomarker panel they identified that can predict node positive disease at the time of cystectomy. Thus, patients could be more closely considered for neoadjuvant chemotherapy. The COXEN assay uses a 31-gene biomarker set that can similarly predict for overall survival and need for neoadjuvant therapy.
The challenges to personalized medicine include few prospective biomarker validation studies. The biomarker requires studies that address clinical utility and assess benefit of gene-guided management. There are also regulatory hurdles, reimbursement challenges and the need for better physician and patient education.
Presented by Dan Theodorescu, MD, PhD at the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.
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