Biomarkers for active surveillance, predicting clinical risk, diagnosis and prognosis, treatment response, and clinical outcomes of prostate cancer were the focus of 29 presentations at the recent 2014 Genitourinary Cancers Symposium, held in San Francisco, CA, January 30 to February 1.
Prostate cancer is second only to skin cancer as the most frequently diagnosed cancer in men and second only to lung cancer in cancer deaths. An estimated 233,000 men will be newly diagnosed with prostate cancer in 2014, and 29,440 will die of the disease. Black men, in particular, have a 60% higher incidence rate of prostate cancer than non-Hispanic whites, and have higher death rates.1
A biomarker is defined as “a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.”2 Biomarkers for cancer are generally categorized as prognostic, predictive, or pharmacodynamic3 and, in prostate cancer, can be detected in tissue, blood, seminal plasma, or urine.4
In drug development, biomarkers can be used for target verification, early compound selection, pharmacodynamic assays, patient selection for clinical trials, or a surrogate endpoint in drug approval. In patient care, use of biomarkers is tied to a clinical goal, including risk stratification, chemoprevention, screening, diagnosis and classification, prognosis, prediction of treatment, and therapy tracking and posttreatment surveillance.3
Biomarkers form the core of personalized—or precision—medicine, which is largely driven by genetics. The Collaborative Oncological Gene-environment Study (COGS), a consortium of more than 160 research groups, is the largest genotyping project worldwide to target identification of genetic alterations that influence risk of common cancers. COGS recently found 23 new prostate cancer susceptibility loci at genome-wide significance, bringing the total number of single nucleotide polymorphisms (SNP) to 77. These SNPs account for approximately 30% of those with a familial risk for prostate cancer.5
“The top 1% of men in the highest risk stratum have a 4.7-fold greater risk relative to the population average, and the top 10% of men have a 2.7-fold greater risk,” the study authors wrote. “The SNP-based prostate cancer risk profile now available should therefore be able to distinguish men at a clinically meaningful level of risk.”5 These findings have implications for creating targeted screening and prevention programs, as well as for facilitating population risk stratification for clinical studies and for treatment.
Such discoveries also allow clinicians to fine-tune available therapies. For example, number 5 on the American Society of Clinical Oncology’s 2013 Top 5 Choosing Wisely list is “don’t use a targeted therapy intended for use against a specific genetic aberration unless a patient’s tumor cells have a specific biomarker that predicts an effective response to the targeted therapy.”
One of the challenges in diagnosing prostate cancer is the nonspecificity of prostate-specific antigen (PSA) as a serum biomarker, leading to the potential both for underdiagnosis and overtreatment.