UC San Francisco has been awarded a major federal grant to "transform and revolutionize" the treatment of prostate cancer, the second most common form of cancer among American men.
The grant, totaling $9.45 million over three years, is intended to overhaul through precision medicine the clinical management of prostate cancer, particularly for men newly diagnosed with the disease.
In the project, scientists will develop and validate a novel risk-prediction model to provide better information about the patient's true risk of cancer progression.
For the second component, the UCSF team will implement a decision support intervention to help men better determine whether to treat or to monitor their disease. Featuring a secure website and live coaching support from genetic counselors, patients will receive a highly personalized summary of their cancer risk and management options.
Currently, many men undergo avoidable treatment for prostate cancer. Active surveillance is an alternative option for patients when the prostate biopsy indicates their cancer is unlikely to spread quickly. But in as many as 30 percent of cases, the cancer may turn out to be more aggressive than it initially appeared at the time of diagnosis. This limits the number of men and their physicians who feel comfortable choosing active surveillance.
By providing men with a comprehensive, personalized assessment of their cancer risk along with an innovative support system to help them understand their results, the project is designed to address incomplete patient information as well as poor understanding among patients about the implications of their treatment decisions. In the process, the study would fundamentally change the treatment and decision process for men with apparent low-risk disease.
The grant is called a Department of Defense Prostate Cancer Research Program Transformative Impact Award.
"Through early detection and treatment of aggressive prostate cancers, death rates from this disease have fallen 40 percent over the past 20 years, but the price of this success has been many thousands of men with low-risk prostate cancer who have undergone unnecessary surgery, radiation and other treatments -- all of which carry risks of potentially serious side effects," said Peter R. Carroll, MD, MPH, professor and chair of the UCSF Department of Urology and principal investigator of the new study.
"Our inability to reliably identify which tumors will actually progress, including the ones that appear to be low-risk, causes significant anxiety and uncertainty among men and their physicians," Carroll said. "This anxiety is a significant impediment to broader use of active surveillance with low-risk prostate cancer."
UCSF was selected from 52 institutional applicants for the grant funded by the Department of Defense Prostate Cancer Research Program.
The award "was envisioned to transform and revolutionize the clinical management of prostate cancer," said Colonel Wanda Salzer, MD, director of the Congressionally Directed Medical Research Programs. "Dr. Carroll's multi-institutional project epitomizes the integration of new technologies in medicine and communications to help patients understand their disease risk and select optimal treatment options."
Despite ongoing declines in prostate cancer death rates, screening for prostate cancer remains controversial -- and low-risk, indolent cancers are often over-treated, in part due to concerns that a biopsy may not fully reflect the aggressiveness of the tumor.
"Currently, prostate cancer management decisions are made in the setting of both incomplete information and, frequently, poor understanding of what information is available," said project co-principal investigator Matthew R. Cooperberg, MD, MPH, a UCSF associate professor of urology and epidemiology & biostatistics. "As a result, many men rush into decisions they may later regret, and many suffer side effects of avoidable treatments, leading to poor satisfaction."
"We will address the first problem by developing a multi-dimensional, personalized risk assessment tool to give men a better sense of the risk that their cancer may progress," Cooperberg said. "We will also develop an innovative decision support intervention, using trained counselors, to help men understand the complex information incorporated in the risk tool before they make their treatment decisions."
To develop the risk prediction model, the UCSF team will analyze data and prostate tissue derived from 945 men from the archives at UCSF. The model will be validated among men participating in the national, community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) prostate cancer registry.
Co-principal investigator June M. Chan, ScD, said the project will leverage existing research strengths, "including our outstanding and dedicated staff, tissue repository and longitudinal clinical database, national CaPSURE study, prior collaborations with local patient advocates and bio-medical industry partners, and our terrific multi-disciplinary faculty."
"This award mechanism was refreshing because it was broad enough in scope and large enough in support to allow us to conceptualize addressing a question all the way from the bench to the bedside and into the community," said Chan, professor of epidemiology and biostatistics and urology. "This is a unique strength of this project in that it embraces the full translational research pathway, and aims to not only create a novel personalized medicine intervention, but follows through to develop and evaluate the impact of this intervention in the community setting."
The UCSF team will tap the expertise of co-investigator Jeffrey Belkora, PhD, a UCSF faculty member and director of Decision Services with the UCSF Helen Diller Family Comprehensive Cancer Center. Belkora has developed and launched at UCSF and in community settings around the country decision support tools and interventions for women with breast cancer.
The decision support intervention will be developed at UCSF, the UCSF-affiliated San Francisco VA Medical Center, and San Francisco General Hospital and Trauma Center. It will then be evaluated in a clinical trial at five clinical practice sites around the United States.
The UCSF team includes project director Imelda Tenggara-Hunter, director of Research Resources in the Dept. of Urology; John Witte, PhD, professor of epidemiology & biostatistics and urology; Jeffrey P. Simko, MD, PhD, associate professor of pathology and urology; John Neuhaus, PhD, professor of epidemiology & biostatistics; Erin Van Blarigan, ScD, a postdoctoral scholar in the department of epidemiology & biostatistics; Stacey Kenfield, ScD, an assistant adjunct professor in the UCSF urology department; Jeanette Broering, RN, PhD, MPH, director of data operations in the urology department; and Laura Dunn, MD, associate professor in the UCSF psychiatry department and director of psycho-oncology in the urology department.
The project also includes industry partners GenomeDx and Genomic Health Inc.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospital.