Tests for the early detection of prostate cancer
Dr. Catalona was the first to show that the PSA blood test could be used as a first-line screening test for prostate cancer. He directed a PSAbased screening study involving more than 36,000 men and lasting 12 years that helped characterize the operating characteristics of the test. He led the registration studies for FDA approval of total PSA, free PSA and the new Prostate Health Index (phi) blood test. Since his original paper on PSA screening was published in the New England Journal of Medicine in 1991, the prostate cancer death rate in the U.S. has decreased by more than 47%.
Focusing on genetic variants
Prostate cancer is among the most heritable of cancers, and recent studies have identified approximately 100 genetic variants associated with prostate cancer risk. However, taken together they explain only about 35% of the inherited risk. Thus, there is uncertainty about which genetic variants cause life-threatening prostate cancer, and the genetic basis of prostate cancer aggressiveness remains an important unanswered question.
Dr. Catalona was involved in the study that discovered the first prostate cancer risk variant, as well as in subsequent studies identifying approximately 12 other risk variants. Today, he is leading studies aimed at identifying germline genetic markers associated with prostate cancer and is collaborating with the International Consortium for Prostate Cancer Genetics studies in familial cases. In clinical research, he has performed studies on the nerve-sparing radical prostatectomy in his series of nearly 7,000 patients.
Examining active surveillance
Dr. Catalona's current main research project involves studies of men enrolled in active surveillance programs (AS) to develop a panel of biomarkers that will aid in distinguishing which men can safely enroll in AS versus those who are destined to fail AS and therefore should undergo immediate treatment. These studies will advance our fundamental understanding of prostate cancer. The project is designed to answer three important research questions:
- Who needs to be biopsied?
- Who needs immediate treatment?
- What cell-signaling pathways are important for prostate cancer aggressiveness?
Answering these questions will improve the treatment options and lives of prostate cancer patients and help reduce overtreatment.
The relationship between genetic variants and AS
Dr. Catalona has brought together investigators from 18 participating sites across the U.S. and the world. His research group will genotype variants in 9,395 men enrolled in AS programs run by collaborators who have agreed to provide DNA samples and clinical data on their patients.
The resulting data will be used in studies with four specific aims:
- Discovery: To evaluate the relationship between germline genetic variants and AS failure among 6,850 prostate cancer patients enrolled in AS programs
- Validation: To validate the AS failure-associated variants found in Aim 1 in an independent cohort of 2,545 AS patients
- Functionality: To identify cellsignaling pathways associated with AS failure
- Prediction: To use the findings from the previous aims to develop clinical algorithms to prospectively identify men at high risk for AS failure
Improving treatment through personalized medicine
The impact of this research will be to translate the technological advances in genomics to "precision" medicine in prostate cancer. This project will deliver DNA-based biomarkers for use in algorithms to improve the lives of men diagnosed with low-risk prostate cancer. This will be achieved through innovative integration of existing information on genetic variants associated with prostate cancer with cutting-edge genotyping/sequencing technology and sophisticated statistical methods to identify and validate genetic variants associated with failure of AS.
Application of this information will create practical, actionable algorithms that aid in identifying men with low-risk prostate cancer who can be managed safely with AS versus those who need immediate treatment.
This project will:
- Reduce overtreatment of prostate cancer
- Identify new biomarkers for other treatment decisions or for targeted screening
- Identify the signaling pathways that make some prostate cancers more aggressive
- Identify molecular targets for pharmaceutical manipulation and/or possibly provide clues for new prostate cancer prevention strategies and overall, advance our understanding of germline genetic factors that influence prostate cancer aggressiveness