Clinical trial tests precision radiotherapy for recurrent prostate cancer

Prostate cancer imaging

This CT scan illustrates a proposed stereotactic body radiation therapy (SBRT) treatment plan for a patient with a prostate tumor that has recurred locally after radiation therapy, circled in purple. The bladder is circled in yellow, and the rectum is circled in brown. The scale on the left indicates the total radiation dose, with red denoting the highest dose, and gray denoting no radiation. Standard radiation therapy can target the entire prostate, but SBRT targets only recurrent tumors. In this patient, the recurrent tumor receives the highest dose of radiation, while the bladder and rectum receive little to no radiation.
Image courtesy of Dr. Citrin 

Treating prostate cancer that recurs after standard radiation therapy is challenging. Currently available options, such as cryotherapy, which involves freezing the prostate, or surgery to remove the prostate, can trigger urinary and bowel problems as well as other side effects. Center for Cancer Research investigators are launching a phase I trial of a new, highly precise technique to treat prostate cancer that has recurred locally after radiation. The hope is that this type of treatment will have fewer side effects than the current standards of care.

The technique in this trial combines stereotactic body radiation therapy (SBRT) with advanced molecular imaging to guide the delivery of radiation directly to tumors in the prostate. This specificity may not only minimize side effects, but also enable physicians to deliver higher doses of radiation than with other forms of radiation therapy, resulting in a shorter treatment regimen. Led by Deborah Citrin, M.D., of CCR’s Radiation Oncology Branch, the trial will determine the maximum effective dose of radiation that patients can safely tolerate. Her team began recruiting participants in October.

“This is one of the few examples of using a molecular imaging technique to help guide treatment,” Citrin says. “We’re using top-notch imaging to give the most focal treatment possible to prevent growth of the tumors and prevent side effects.”

In this trial, a radiolabeled molecule binds to specific proteins on cancer cells so that the molecule can be seen on a positron emission tomography (PET) scan. The PET scan is used to determine where to aim the radiation treatment.  The radiolabeled molecule being used is known as 18F-DCFPyL, which binds to the prostate-specific membrane antigen (PSMA) found on prostate tumors.

“There’s a lot of excitement about PSMA imaging as a way to tailor treatment for prostate cancer,” Citrin says. PSMA expression has been strongly correlated with aggressiveness and recurrence of prostate cancer, making 18F-DCFPyL and other radiolabeled molecules that target PSMA promising for detecting prostate tumor regrowth. Studies have shown that these radiolabeled molecules can accurately latch on to PSMA in recurrent prostate tumors in patients who had previously received standard radiation therapy.

The trial is enrolling up to 52 patients, all of whom will undergo an MRI scan, 18F-DCFPyL imaging and a prostate biopsy to locate recurrent tumors. For participants who have received external beam radiation therapy (EBRT), which involves a machine that aims beams of radiation at the prostate, but haven’t received brachytherapy, which involves planting radioactive seeds in the prostate, SBRT will be delivered only to recurrent tumors.

But for those who have received both EBRT and brachytherapy, SBRT will be delivered not only to recurrent tumors but also at a reduced dose to the entire prostate. Patients who have undergone brachytherapy may be able to tolerate higher doses of radiation, and identifying recurrent tumor on standard imaging tests can be difficult. Targeting the prostate as well as the tumors therefore ensures that these patients receive adequate treatment.

Participants will receive five doses of SBRT over the course of two weeks. A group of several patients will receive one dose of radiation to see how well it is tolerated. Each group of patients will receive a higher dose of radiation than the group before.

Citrin’s team will continue escalating the dosage until they begin observing side effects. “You want to give the highest dose you can to the tumor,” Citrin says. “The hope is that by giving the highest dose to just a small area, that will make it much more tolerable.”

Participants’ response to SBRT will be evaluated through measurements of the levels of prostate-specific antigen (PSA) in their blood every 1 to 3 months for two years. Declining PSA levels suggest tumor regression and rising PSA levels suggest tumor recurrence. During the two-year follow-up period, participants will also respond to questionnaires assessing their quality of life, as well as their urinary, erectile and bowel function.

Citrin credits CCR’s integration of world-class expertise and facilities across multiple disciplines for helping to make the trial possible. “I don’t think this could happen anywhere else,” she says. “It’s taking the strengths of the Radiation Oncology Branch, the Molecular Imaging Program, the Urologic Oncology Branch and the Prostate Cancer Multi-Disciplinary team, and it’s putting it all together in a way to give very precise, focal treatment.”

The Center for Cancer Research is NCI’s internal cancer center, a publicly funded organization working to improve the lives of cancer patients by solving important, challenging and neglected problems in cancer research and patient care.  Highly trained physician-scientists develop and carry out clinical trials to create the medicines of tomorrow by treating patients at the world’s largest dedicated research hospital on the campus of the National Institutes of Health in Bethesda, Maryland. Search all CCR clinical trials, and subscribe to have the latest CCR clinical trials sent to your inbox.

Summary Posted: 12/2017