The addition of the radiotracer fluciclovine to positron-emission tomography (PET) imaging for treatment planning led to superior failure-free survival compared with conventional imaging in men with prostate cancer who had undergone radical prostatectomy and were experiencing biologic recurrence of their cancer, according to the first results of a phase III trial presented at the 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract LBA 1), which is being held virtually.

The initial report from the phase III randomized EMPIRE-1 trial showed that 3-year disease-free survival rates were 75.5% for men whose treatment plan was based on fluciclovine PET imaging vs 63% for men whose treatment plan was based on conventional imaging. EMPIRE-1 is unique in that it studied the role of PET with cancer control as an endpoint.

Ashesh B. Jani, MD

“The decision to offer post-prostatectomy radiation therapy is complex, because conventional imaging can leave unanswered questions on the best approach to treatment planning,” said lead author Ashesh B. Jani, MD, Professor of Radiation Oncology at the Winship Cancer Institute of Emory University.

Several studies have shown that more advanced imaging techniques, including fluciclovine PET and prostate-specific membrane antigen (PSMA) PET, can reveal the presence of  malignant lesions that are not found with conventional imaging, including bone scans, computed tomography (CT) scans, or magnetic resonance imaging (MRI).

“This research shows that integrating advanced molecular imaging [with fluciclovine PET] into the treatment planning process allows us to do a better job selecting patients for radiation therapy, guiding radiation treatment decisions and planning, and, ultimately, keeping patients’ cancer under control,” said Dr. Jani.

“This is the first study of its kind to look at the role of PET in influencing a cancer control endpoint. That is a very high bar for an imaging study,” stated co–principal investigator of this study, David M. Schuster, MD, a nuclear radiology specialist and Professor at Emory University.

David M. Schuster, MD

Fluciclovine is approved by the U.S. Food and Drug Administration (FDA) as a radiotracer for the restaging of recurrent prostate cancer, and is included in the National Comprehensive Cancer Network^® (NCCN^®) Clinical Practice Guidelines in Oncology. However, it is not widely used as a standard for planning treatment in patients with recurrent prostate cancer. Other PET radiotracers are also under study in prostate cancer, including PSMA.

Study Details

The Emory Molecular Prostate Imaging for Radiotherapy Enhancement (EMPIRE)-1 trial enrolled 165 men who had undergone radical prostatectomies but subsequently had rising prostate-specific antigen (PSA) levels, signaling the presence of more aggressive cancer. All patients enrolled in the trial underwent conventional imaging with bone scans, CT, or magnetic MRI for initial treatment planning that were negative for detecting cancer in the bones or outside the pelvis. Study participants were stratified for risk factors, including the presence or absence of extracapsular spread, seminal vesicle invasion, or positive nodes, and intent to use androgen-deprivation therapy.

The men were randomly assigned to two groups: the first received radiation based on conventional imaging, and the second underwent fluciclovine PET imaging, and treatment was planned according to those findings.

The following PET findings changed treatment decisions as indicated:

• Extrapelvic uptake: radiotherapy aborted
• Pelvic nodal uptake: radiotherapy administered to prostate bed and pelvis, with boost at site of uptake
• Prostate bed–only uptake: radiotherapy given to prostate bed and boost at sites of uptake
• No radiotracer uptake: prostate bed received radiotherapy with no boost.

The boost consisted of 54 to 56 Gy to pelvic nodes and 70 to 76 Gy to the prostate bed.

“This study is unique. Having a  cancer control endpoint is rare. We hardwired treatment decisions into the study schema,” explained Dr. Jani.

Toxicity was reported during radiotherapy and every 6 months, and cancer control data were reported every 6 months.

Study Results

The primary endpoint was 3-year failure-free survival, and the patients whose treatment was planned using fluciclovine PET had a significantly higher rate: 75.5% vs 63% for those whose treatment was planned according to conventional imaging results (P = .003), an absolute difference of 12%. The superiority of fluciclovine PET imaging persisted at 4 years: 75.5% for the experimental arm vs 51.2% for the control arm (P < .001), a 13% absolute difference.

At a median follow-up of 3 years, provider-reported toxicity showed no significant differences between treatment arms for grades 1, 2, 3, and 4 acute or late genitourinary or gastrointestinal toxicity. “This suggests that treatment to PET-directed volumes was tolerable,” said Dr. Jani. Patient-reported toxicity will be presented in the future.

“This is an important trial,” Dr. Schuster said. “The reason we did this research was because we were frustrated that we could not get better cure rates for patients with rising PSA after radical prostatectomy. We thought one of the factors involved may be the sensitivity of the imaging tests used to plan radiation therapy. We hoped that this new PET test, with greater sensitivity to detect prostate cancer, would translate to a better cure rate as well. We believed there would be some effect, but we were pleasantly surprised by the strength of the findings.”

Drs. Jani and Schuster and co-investigators will continue to explore more sophisticated imaging techniques in prostate cancer. The next study, EMPIRE-2, will randomly assign patients who have rising PSA post-prostatectomy to fluciclovine PET vs PSMA PET for treatment planning.

“Fluciclovine PET has become the best available test,” said Dr. Schuster. “But now there’s an even newer kid on the block. In EMPIRE-2, we’re building on the results of EMPIRE-1 by comparing PSMA with fluciclovine to see which one of these radiotracers improves cancer control better.” That study is already in progress and allows precise dose escalation, he added.

Disclosure: For full disclosures of the study authors, visit plan.core-apps.com.