Adding the 18F-fluciclovine PET radiotracer to help guide radiation treatments for recurrent prostate cancer can improve disease-free survival rates, results from a Phase III study show.
"The decision to offer post-prostatectomy radiation therapy is complex, because conventional imaging can leave unanswered questions," said investigator Ashesh B. Jani, MD, MSEE, FASTRO, Professor of Radiation Oncology at the Winship Cancer Institute of Emory University in Atlanta, during a briefing at the ASTRO 2020 Annual Meeting (Abstract LBA-1).
As co-principal investigator for the randomized Phase II/III EMPIRE-1 trial, Jani said that 75.5 percent of prostate cancer patients with PSA levels indicating cancer recurrence after prostate removal were disease-free at 3 years when imaging included fluciclovine, and the improved rate continued for at least 4 years. The rate among patients who were scanned using traditional imaging was 63 percent. The FDA approved the use of fluciclovine in 2016.
"At 3 years, the group getting treatment guided by PET fluciclovine had a 12 percent better cancer control rate, and this persisted at 4 years as well, with a 24 percent improvement," Jani said. "We think the improvement was seen because the novel PET allowed for better selection of patients for radiation, better treatment decisions, and better radiation target design. Integrating advanced molecular imaging allows us to do a better job of selecting patients for radiation therapy, guiding radiation treatment decisions and planning, and ultimately, keeping patients' cancer under control."
"This is the first study of its kind to look at the role of PET in influencing a cancer control endpoint," added David M. Schuster, MD, a nuclear radiology specialist and Professor at Emory University who collaborated with Jani on the study as co-principal investigator. "That's a very high bar for an imaging study."
Although previous PET studies have led to changes in how prostate cancer is managed, this is the first major study to show improvement in outcomes.
"This is a jump ahead of the traditional way of looking at things," said Jani. "It helps us to pinpoint the location of the prostate cancer recurrence."
Methodology
The EMPIRE-1 trial enrolled 165 prostatectomy patients who later showed abnormal PSA levels. All initially underwent conventional imaging before being randomized to receive either radiation therapy based on initial treatment plans or fluciclovine-guided PET scans and standardized treatment.
Three years later, 75.5 percent of patients in the fluciclovine arm had disease-free survival compared to 51 percent of subjects who underwent traditional PET scans. There were no significant differences in severe genitourinary or gastrointestinal side effects among the patients.
Researchers attributed the improved outcomes to better patient selection by excluding patients with extrapelvic disease who are more susceptible to failure, as well as better definition of the tumor and treatment field.
"The reason we did this research was because we were frustrated that we could not get better cure rates for patients with this type of cancer," said Schuster. "We thought one of the factors involved may be the sensitivity of the imaging tests. We thought this new PET test would translate into a better cure rate. We were pleasantly surprised by the strength of the findings."
The collaborative team led by Jani and Schuster is already investigating whether a newer type of PET scan, which uses a radiotracer to target a receptor on the surface of prostate cancer cells, could be even more effective than fluciclovine in improving cancer control. The newer scan, PSMA, is not yet FDA-approved.
"Before a patient is considered for radiation therapy to treat prostate cancer that has returned after surgery, the doctor should not rely on traditional imaging alone, but should also use advanced molecular imaging," Jani added. "Doing so will help determine if radiation therapy is appropriate and, if so, more precisely plan how to target his disease."
No Longer High-Risk?
Recent advances in testing for prostate-specific membrane antigen (PSMA), coupled with improved PET/CT accuracy, have all but pushed what has been high-risk prostate cancer into a lower-risk category, according to another study presented at the ASTRO meeting.
A paper presented by Martin Ma, MD, PhD, a researcher at the University of California, Los Angeles, suggested that improvements in how prostate cancer is diagnosed, imaged, and treated have resulted in patients who no longer fit in the high-risk category.
"CT is the only FDA-approved scan for prostate patients in the U.S., but PSMA PET/CT imaging has exploded around the world due to its much higher sensitivity and specificity," Ma noted. "Fortunately, based on clinical trials led out of UCLA, UCSF, and other centers, I am hopeful that these molecular imaging modalities can soon be added to our toolbox to better personalize our treatments."
He and his colleagues showed that PSMA PET/CT correctly flagged 19.7 percent of patients with regional PET positive nodal disease, and 9.4 percent with metastatic disease on PET/CT.
"Although these sites were not uniformly biopsy-proven sites of metastatic disease, it is probable that, based on prior data, 85-98 percent of these lesions are likely to be prostate cancer," Ma explained.
Daniel Spratt, MD, Professor of Radiation Oncology and Associate Chair of Clinical Research, commented on the findings for ASTRO.
"What is perplexing about this data is that the UCLA group has previously suggested that grade group 5 patients benefit the most from local dose escalation to the prostate gland. This is interesting, given their current findings demonstrate that nearly 30 percent of patients with grade group 5 disease have regional or distant metastatic disease," he said. "Clearly, we continue to have a lot to understand about how best to manage PSMA PET/CT detected N1 or M1 disease."
The implications are thought-provoking, he said. It is estimated that 15-20 percent of men with high-risk prostate cancer will develop metastatic disease with long-term follow-up. It remains highly suggestive and probable that many of them harbored pre-existing regional or metastatic disease that now can be, in part, detected by PSMA PET/CT.
"So, the question remains: for men without evidence of N1 or M1 disease on PSMA PET/CT, what is their natural history with current standard of care therapy? No one knows yet," Spratt noted. Additionally, for patients with nodal or distant disease only on PSMA PET/CT, it remains unclear if they should be treated like a de novo mHSPC patient with androgen deprivation therapy, next-generation AR-signaling inhibition or chemotherapy, and treatment of the primary [site]."
Kurt Samson is a contributing writer.