The National Cancer Institute has awarded Keck School of Medicine radiologist Hossein Jadvar nearly $3.4 million over five years to study the potential of positron emission tomography combined with computed tomography, or PET-CT, in the monitoring of metastatic prostate cancer during treatment.
Today, oncologists monitor how well patients are responding to prostate cancer treatment by measuring the levels of prostate-specific antigen, or PSA, in patients’ blood. An elevated PSA level can mean that cancer is growing. But PSA is far from a perfect cancer gauge: Other non-cancerous conditions may elevate PSA, while some cancers do not raise PSA. Other imaging tests, such as bone scans, are not accurate enough and cannot show soft-tissue disease.
Jadvar believes that PET imaging will provide physicians with better information about patients’ progress during treatment.
He also hopes it will help better predict patients’ outcomes, providing more realistic expectations about the success of therapy.
“Prostate cancer is a major health problem in men, and it will only become a bigger issue in the future, as life expectancy is increasing,” said Jadvar, associate professor of radiology at the Keck School. “We need to improve the way we evaluate prostate cancer patients.”
Radiologists use PET to get a unique image of the whole body. When used in patients with cancer, it can detect places where cancerous cells have spread, even if they are far from the original tumor.
For this study, Jadvar will use PET together with a chemical called [F-18] fluorodeoxyglucose, or FDG, a form of sugar marked with a radioactive tracer.
Radiologists inject the FDG into the patient before the PET scan.
That enables the PET scan to show if there are any hot spots in the patient’s body where the sugar is being metabolized quickly. These spots may indicate cancer, Jadvar explained, because cancerous cells use sugar more than healthy cells.
Jadvar will use FDG PET with CT to provide even more detailed information than would be available through FDG PET alone.
Men with newly diagnosed prostate cancer that has metastasized outside the prostate capsule will be invited to participate in the study. Jadvar will look at PET’s usefulness both in men who are treated with androgen-ablation therapy as well as those who are treated through chemotherapy.
Androgen-ablation therapy, also called androgen-deprivation therapy or simply hormone therapy, uses either drugs or surgery to lower levels of male hormones—such as testosterone—in the body. Male hormones can cause prostate cancer cells to grow, and suppressing the hormones can stop or stunt their growth.
In men whose cancer does not respond to androgen deprivation, oncologists usually prescribe chemotherapy to control the cancer’s growth.
Through FDG PET-CT, Jadvar wants to see objectively how well both androgen ablation and chemotherapy work. While patients are still receiving treatment, Jadvar will conduct the imaging studies.
In this study, results of the imaging studies will not alter or influence patients’ course of treatment.
In all, Jadvar will recruit 160 men who are undergoing androgen-ablation therapy and another 160 who are undergoing chemotherapy. Each participant will receive four FDG PET-CT scans during therapy.
Patients will be scanned from the top of the head to below the knees. Physicians also will monitor patients’ PSA levels.
Jadvar hopes that FDG PET-CT scans will enable him to see whether tumors are responding to therapy as soon as treatment begins and throughout the therapy. If the imaging can show how well hormone therapy and chemotherapy work—while therapy is still underway—oncologists may come to rely on FDG PET-CT to better guide treatment decisions in the future.
The imaging might also help shine light on whether metastases located in one part of the body, such as the brain, respond differently to treatment than those in other parts of the body, such as bone. And because FDG PET shows tumor metabolism, the FDG PET scans will be able to show whether treatment is stunting a tumor’s activity—even when CT scans show no change in a tumor’s size.
When data from the study have been analyzed, Jadvar also hopes that results will enable physicians to associate findings on FDG PET scans to patients’ outcome.
Jadvar explained that even in men with metastatic prostate cancer who initially respond well to androgen-ablation therapy, the cancer eventually grows resistant to the hormone suppression and spreads despite the therapy. That usually takes about 18 months to happen, Jadvar said. “But we cannot predict exactly when that hormone-refractory stage will happen,” he said. “If we know that a man will develop the hormone-refractory stage in a year, for example, that information may be helpful to the clinician, who can employ other treatments earlier to delay the hormone-refractory stage and possibly enhance overall survival.”
Meanwhile, men whose metastatic prostate cancer does not respond to hormone treatment survive for an average of eight months, Jadvar said, but their lifespan may be significantly more or less.
“I’m hoping FDG PET will help better predict how long they are going to live,” he said. “It’s important to be honest with a patient, and for counseling, it’s important to tell them the truth—and give them the best information we have on their lifespan.”
Jadvar will work with clinicians at the USC/Norris Comprehensive Cancer Center and Hospital and LAC+USC Medical Center on the study. Keck School clinicians include David Quinn, Jacek Pinski, Ana Aparicio and Eila Skinner, along with Przemyslaw Twardowski, oncologist at the City of Hope.
Susan Groshen, biostatistician at the Keck School, and radiologists Peter Conti and Robert Henderson, will be co-investigators as well. Jadvar noted that Edward Grant, chair of radiology, has been a key supporter for the project.
Scans will be conducted at the USC PET Imaging Science Center located at the Healthcare Consultation Center.