Using Years of Clinical Data to Improve Prostate Cancer Treatment
Summary
- A research team at Sylvester Comprehensive Cancer Center is pouring over clinical data to create a new approach for prostate cancer patients.
- Dr. Alan Pollack and colleagues are developing and testing a model that uses MRI techniques and liquid biopsy markers to guide physicians’ decisions about prostate cancer therapy.
- The team plans to create a model that optimizes treatment for prostate cancer patients throughout the world.
Patients with intermediate- to high-risk prostate cancer face several significant risks, including relapse after completing treatment. Typically, these patients are treated with androgen deprivation therapy—a type of hormone therapy—in combination with radiotherapy to increase response, reduce metastatic risk and improve survival.
Hormone therapy induces a male menopause and is associated with significant systemic side effects, including an increased risk of thromboembolic events, metabolic syndrome, body changes, bone density reduction, erectile dysfunction and anemia, among other significant effects.
Today, oncologists have few tools with which to make key decisions on intensifying versus de-intensifying hormone therapy. But a research team at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, is building on years of clinical data to create a new approach that could reshape treatment for prostate cancer patients.
The multi-principal investigators team, led by Alan Pollack, M.D., Ph.D., a professor of radiation oncology at the Miller School, received a $2.6 million, five-year R01 grant from the National Cancer Institute (NCI) to develop and test a model that uses MRI techniques and liquid biopsy markers to guide physicians’ decisions about prostate cancer therapy.
“What we’re trying to do is gather all this multimodal data and find early measures of treatment response that can guide early intensification or de-intensification of treatment,” said Benjamin Spieler, M.D., an assistant professor of radiation oncology at the Miller School and a co-principal investigator, along with Sylvester’s Radka Stoyanova, Ph.D., professor of radiation oncology at the Miller School.
“It’s personalizing the treatment for patients in order to derive optimal outcomes,” said Dr. Stoyanova.
Prostate Cancer Decision Making
Approximately 30% to 40% of patients with intermediate- to high-risk prostate cancer will relapse within five to 10 years of completing treatment with either prostatectomy or radiotherapy. About half the patients who develop distant metastasis from prostate cancer start with androgen-sensitive disease.
The physician’s decision tree for treatment revolves around the intensification or de-intensification of hormone therapy. Options include no hormone therapy, short-term hormone therapy for six months or long-term hormone therapy for two years. Second-line hormone therapy agents may be added, as well.
The research aims to reduce the risk of distant metastasis in selected patients by informing early responses to treatment.
Over the past 15 years, Dr. Pollack has led four clinical trials on prostate cancer that built an extensive and unmatched repository of imaging and biologic samples that form the foundation of this new research. In addition to data from the Sylvester clinical trials, the team will also use external data from the NIH to validate findings.
“From nearly 16 years ago, we were devising clinical trials that incorporated the collection of MRI imaging data and blood biosamples, with the goal of improving response through the development of models of prostate cancer response to radiotherapy and hormone therapy,” Dr. Pollack said. “We anticipated the importance of correlative studies that were built into our clinical trials, making our strategy a perfect fit for this NCI-funding mechanism.
Until now, these trials have been funded from a variety of sources, including the NCI, Florida Department of Health, Sylvester’s Intramural Funding Program and philanthropy.
Advanced MRI and Liquid Biomarkers
Dr. Stoyanova, the director of imaging and biomarkers research in the Department of Radiation Oncology, focuses on quantitative imaging. Using MRI images collected before and after radiation treatment in clinical trial participants, Drs. Stoyanova, Pollack and Sanoj Punnen, M.D., co-chair of Genitourinary Site Disease Group at Sylvester and professor and vice chair of research at the Desai Sethi Urology Institute, pioneered technology to map prostate tumor characteristics and better identify the highest-risk cancers.
Dr. Stoyanova’s team of imaging and AI scientists has developed a comprehensive platform for longitudinal data analysis to assess how changes in tumors throughout radiation treatment relate to treatment outcomes.
Another key component of the new research utilizes biologic samples from the clinical trials, including liquid biopsies of circulating tumor cells taken before and after radiation therapy, as well as hormone therapy. Circulating tumor cells are biomarkers for metastatic potential and response.
The new model the researchers are developing will enable physicians to make adjustments to hormone therapy based on a patient’s risk factors and early response.
“If a patient is responding nicely to long-term androgen deprivation therapy a few months in, based on the biomarkers the team will develop, then the doctor could decide to decrease the length of treatment, which will save the patient from unpleasant side effects,” Dr. Stoyanova said.
Toward the end of the five-year grant, the team will refine the model in a new, ongoing protocol led by Dr. Spieler called UAdapt. Researchers will modify the intensity of treatment for enrolled patients.
Ultimately, the team plans to create a model that optimizes treatment not only for prostate cancer patients at Sylvester but also worldwide. While the data enabling this study comes uniquely from Sylvester, physicians anywhere could potentially apply the model using quantitative imaging and blood biomarker information.
The researchers emphasized the importance of the long-term vision and teamwork in making this grant possible.
“This is why we enter science or become physicians, to have a discovery or study that we then can give back to our community,” Dr. Spieler said. “We are working to create a model that can be applied beyond our own boundaries, outside of our particular niche, across the country and hopefully the world.”
Tags: cancer research, Department of Urology, Desai Sethi Urology Institute, Dr. Alan Pollack, Dr. Benjamin Spieler, Dr. Radka Stoyanova, prostate cancer, prostatectomy, Radiation oncology, urology