One Discovery at a Time: An Update on My Ongoing Prostate Cancer Research and My Hopes for the Future
by William J. Catalona, M.D., Medical Director of the URF
My patients and Urological Research Foundation donors frequently ask about my research projects and professional educational activities. Contributions to the URF support my research, so I want to update QUEST readers on my ongoing research projects, and I have some good news to report. I’ll begin with my previous research work and then follow with where we are now and where we are going.
Prostate-specific antigen (PSA) as a first-line screening test for prostate cancer
Before our work in this area, it was not believed that PSA could be used as a first-line screening test for prostate cancer. We were the first to show that the PSA blood test is the best test available for early detection. This ushered in the PSA screening era and was a precursor of the study that led to FDA approval of PSA as an aid to early detection of prostate cancer.
Now, data from the U.S. Cancer Registries shows more than a 50% decrease in prostate cancer mortality during the PSA screening era. Despite controversy, most professional organizations now recommend a shared decision-making process for PSA screening. My research group subsequently led the pivotal studies that achieved FDA approval of the Free PSA test and the Prostate Health Index test (PHI) to improve the accuracy of PSA screening.
Inherited genetic variants associated with prostate cancer and its aggressiveness
Family history is a strong risk factor for prostate cancer, but there remains uncertainty about which genetic variants and mutations cause life-threatening prostate cancer. The genetic basis of prostate cancer aggressiveness remains an important unanswered question.
My research group participated in the early studies focusing on the genetics of prostate cancer susceptibility and aggressiveness, and we continue to pursue these studies as more powerful genetic technology emerges. Our research group collaborated on the first study that discovered the most
important common genetic variants on chromosome 8 that increase the risk of prostate cancer. This and other work from our collaborators has increased the knowledge of genetic factors associated with the more aggressive types of prostate cancer and may have practical future applications for targeted screening and personalized medicine.
The primary goal of my current research is to improve the care of patients with prostate cancer through reducing both overtreatment and under-treatment of their cancer. Our research team is working to develop evidence-based ways to better screen men for prostate cancer, as well as to improve management of men diagnosed with the disease. This is especially critical in the areas of active surveillance and early active treatment, and determining which path is best for each person facing prostate cancer.
At present, we are working on the statistical analysis of a genetic project involving a study population of more than 7,000 patients from 28 sites in the U.S., Canada, U.K., Europe, and Australia. We will soon report on our results of our genome-wide association study of common genetic variants associated with time to withdrawal from active surveillance for prostate cancer in patients whose tumor was found to be progressing while on watchful waiting.
Our preliminary analysis suggests that we have discovered several new genetic variants that ultimately could be incorporated into a clinical test to aid patients in their selection of treatment. This is the culmination of a life project of which I feel some pride.
However, in science, after a research group makes what they think is a discovery, it is important to replicate the findings in an independent patient population and then move on to study it prospectively. To this end, we are currently engaged in discussions with Oxford and Cambridge Universities in the U.K. and the Northern California Kaiser group and the University of California, San Francisco for validation studies.
For more than the past decade, I have also served as the Principal Investigator of the NU site of the NIH- funded International Consortium for Prostate Cancer Genetics (ICPCG). This multinational research consortium recently published a whole-exome sequencing study (all of the genes that code for the body’s protein production) of aggressive versus non-aggressive prostate cancer. The ICPCG has now merged with the international PRACTICAL Consortium that recently completed a project on rare genetic variants in the ATM gene that makes prostate cancer more aggressive, and I will participate in other studies of different cancer aggressiveness genes.
The knowledge of the genetics of prostate cancer could be important for physicians to offer patients personalized health care, and the Urological Research Foundation will help support these projects.
My other collaborations:
- With Dr. Christopher Haiman of the University of Southern California on an extensive genome sequencing study of aggressive versus non-aggressive prostate cancer and his grant submission, Multiethnic GWAS (genome-wide association study) and TWAS (transcriptome-wide association study) to inform risk prediction for prostate cancer.
- With Professor Chad Mirkin at the NU Center for the Cancer Nanotechnology Excellence on an NIH grant and a Prostate Cancer Foundation Challenge Award to develop a spherical nucleic acid vaccine for immunotherapy of prostate cancer. Dr. Mirkin’s group is planning to move this vaccine concept into a future clinical trial and has submitted a grant application to the NIH to support this work, with me as a collaborator.
- With another multi-institutional research consortium called PCASP (the Prostate Cancer Active Surveillance Project) working on revising our application for a NIH Program-Project grant on improving active surveillance. I will be the clinical leader of one of the main projects within the research, which will expand on my ongoing research projects on germline genetics in patients on active surveillance.
- With Drs. Franklin Gaylis (University of California, San Diego), Ronald Chen (Kansas University), and Jennifer Malin (United HealthCare, Inc.) on a quality-improvement project on active surveillance.
- With Drs. Mitchell Machiela and Steven Chanock of the National Cancer Institute in Bethesda, Maryland working on a project on BRCA2 mutations over time in the development of prostate cancer. As many of you know the BRCA2 gene is related to both breast cancer and aggressive prostate cancer.
- With Drs. Shilajit Kundu and Anuj Desai on a NU Lurie Cancer Center Population Sciences Research Grant called Understanding prostate cancer in men with inflammatory bowel disease.
My research program is supported in part by the Urological Research Foundation with the remainder being supported by grants.
As regards my professional educational activities, I serve on the National Comprehensive Cancer Network (NCCN) Guidelines Panel of Prostate Cancer Early Detection and also served on the NCCN panel to develop temporary guidance during the COVID crisis.
What we hope to learn from the research
The impact of these major research projects will be to translate our genomic research to “precision” medicine in prostate cancer. Through blood, urine, or saliva genomic tests, which are increasingly available, men and their doctors will be to access algorithms that help predict whether or not their prostate cancer will become life-threatening and provide insights into the basic biology of prostate cancer that could yield better future treatments and even strategies for prevention.