A New Approach for Advanced Prostate Cancer

Prostate cancer is the second most common cancer in the U.S. and the second leading cause of cancer death in American men. Overall, one in nine men will be diagnosed with prostate cancer over their lifetime.

When cancer is confined to the prostate, the chance of successful treatment is very high. However, there is no cure for metastatic prostate cancer (cancer that has spread beyond the prostate, or advanced prostate cancer). More than 31,000 men are expected to die from the disease in 2019.

A new research collaboration between NewYork-Presbyterian, Columbia University Irving Medical Center, and the James J. Peters VA Medical Center in the Bronx aims to change the outlook for men diagnosed with metastatic prostate cancer. By employing the latest techniques in precision medicine, the initiative is designed to provide a deeper understanding of advanced prostate cancer and may lead the way to effective new treatments.

The collaboration is supported by a $1 million Challenge Grant from the Prostate Cancer Foundation, a leading funder of prostate cancer research. The grant will allow the institutions to establish a center of excellence in prostate cancer and conduct a clinical trial at the VA to identify personalized treatments based on an individual’s genomic profile.

“A goal of the Prostate Cancer Foundation is to have clinical trials that will bring cutting-edge therapies to patients in the VA system,” says Tito A. Fojo, M.D., Ph.D., a medical oncologist at NewYork-Presbyterian/Columbia University Irving Medical Center and co-investigator of the project.

“The Prostate Cancer Foundation has played a role in the early stages of development for nearly all of the prostate cancer drugs that have been approved over the past few years, and its interests have recently evolved to include immunotherapy and personalized cancer therapy,” says Charles G. Drake, M.D., Ph.D., MPH, director of genitourinary oncology and associate director for clinical research at NewYork-Presbyterian/Columbia University Irving Medical Center and co-director of Cancer Immunotherapy Programs at Columbia, who is a co-principal investigator of the grant. “This grant will allow us to use precision medicine to help predict the best line of treatment for patients.”

Unlike one-size-fits-all treatments developed for the average patient, precision medicine takes individual and group differences into account, including the genetic mutations that may play a role in the development of a person’s cancer. In the VA trial, investigators plan to identify mutations in patients’ prostate cancer tumors and look for existing drugs that may be effective. “Ideally, there’s a drug already approved by the FDA or a drug in development that targets the mutation you have found,” says Dr. Fojo, who is also professor of medicine at Columbia University Vagelos College of Physicians and Surgeons.

Investigators are currently focused on identifying mutations in the BRCA gene, which is associated with increased risk of breast and ovarian cancers in women. “It turns out that the BRCA gene is also important in the development of prostate cancer and pancreatic cancer,” says Dr. Fojo. “If you have a BRCA mutation, you have a greater risk of developing these cancers.”

In fact, 10% to 15% of men with prostate cancer have a BRCA mutation. Luckily, Dr. Fojo says, “we have drugs that work very well in tumors with the mutations.”

The collaboration between NewYork-Presbyterian, Columbia, and the James J. Peters VA Medical Center seeks to go beyond BRCA and other more common mutations. In practical terms, the trial will involve taking biopsies from men with advanced prostate cancer and sending them to Columbia’s labs for RNA sequencing to analyze gene expression patterns. The project will also involve the use of computational tools that can identify the proteins that drive aggressive prostate cancer and match them to drugs or a combination of drugs to target them. Biopsy tissue will also be used to grow balls of tumor cells called organoids that can be used to test the effectiveness of different drugs and help predict a patient’s response to treatment.

The research draws on the expertise of a team of distinguished investigators at NewYork-Presbyterian and Columbia, working in tandem to pursue innovative approaches to treating prostate and other cancers. In addition to Drs. Fojo and Drake, the team includes Michael M. Shen, Ph.D., professor of medicine, genetics & development, urology, and systems biology at Columbia University Vagelos College of Physicians and Surgeons, and a member of NewYork-Presbyterian/Columbia’s Herbert Irving Comprehensive Cancer Center Andrea Califano, Dr, founding chair of the Department of Systems Biology, who developed the computational tools in the trial and is a co-principal investigator of the grant; Susan Bates, M.D., medical oncologist at NewYork-Presbyterian/Columbia and director of Translational Cancer Medicine at Columbia; and Jessica Hawley, M.D., an oncology fellow at NewYork-Presbyterian/Columbia. The VA center of excellence is also benefiting from a financial gift from the Blavatnik Family Foundation.

“Getting our team together came quite naturally,” adds Dr. Shen, who is the principal investigator. “We already had the team members in place. It was really about creating a project that would exploit the specific advantages of what each member could contribute.”

The trial dovetails with other PCF-sponsored efforts at the Department of Veterans Affairs nationwide. The foundation recently announced a partnership with the VA, intended to expand prostate cancer clinical research among veterans all over the country and to speed the development of new treatment options. “The PCF is determined to bring the best prostate cancer therapy to our veterans,” says Dr. Fojo.

The VA provides the ideal setting for such trials. An estimated 12,000 veterans are diagnosed with prostate cancer each year, and it’s the most frequently diagnosed cancer among veterans.

“The average VA physician sees more prostate cancer than the average practitioner,” says Dr. Fojo. “Nearly 100% of their patients are male. And these days, many of our veterans from wars in the 40s, 50s, and 60s are reaching the age where prostate cancer becomes a problem for them.”

The VA also has a uniquely valuable asset: a database that includes the electronic medical records of thousands of veterans treated with standardized treatment protocols. This allows researchers to glean information about the effectiveness of various prostate cancer treatments among specific groups and demographics. It also makes it possible to compare standard treatments with emerging therapies.

“This is a really beautiful data system of the records, treatment outcomes, and laboratory results for thousands of men, which helps enable research and advances in care,” says Dr. Drake.

“It’s an amazing data set. I can tell you how 15,000 veterans did when treated with the standard of care,” Dr. Fojo says. “In the work that we’re doing, we now have amassed so much data that you can actually conduct a clinical trial in a small group of patients and benchmark it against the standard of care and get highly statistically significant results, if you’re dealing with something that’s effective.”

Over time, the data should be able to help researchers predict how successful a treatment will be in individuals, based on their age and other characteristics. “Eventually, we will be able to actually project how effective this is going to be for this 80-year-old Caucasian or this 80-year-old African American versus this 60-year-old Caucasian or this 60-year-old African American,” says Dr. Fojo. “Whether they’re getting it as the first treatment or as the second treatment, all of that data will be available to us.”

Dr. Fojo has a long history working with veterans — his first rotation as a medical student was at a VA hospital.

“Veterans hospitals are the best places in the world to work in as an oncologist,” says Dr. Fojo. “For the veterans, the experience at the VA is more than just the doctor’s visits. It’s a visit to a place where there are a bunch of people you know and who care about you. As a physician, to be part of that feels really good.”

“The most important thing for an oncologist is to give the very best care to their patients,” he continues, “so you can walk away at the end of the day and say, ‘I did the very best that we could have.’ I think any veteran can feel confident that their prostate cancer has been treated optimally and that this will continue and even get better.”