Image-guided radiotherapy with the advanced PET radiotracer fluciclovine (Axumin) reduced treatment failure rates in men with recurrent prostate cancer following surgery, a single-institution randomized study found.
Failure-free survival at 3 years improved from 63.0% for those assigned to standard imaging to 75.5% among those whose treatment decisions were also guided by fluciclovine PET (P=0.003), reported Ashesh Jani, MD, of Winship Cancer Institute of Emory University in Atlanta.
At 4 years, failure-free survival rates were 51.2% versus 75.5%, respectively (P<0.001), according to findings presented at the virtual American Society for Radiation Oncology (ASTRO) annual meeting.
The decision to offer radiation after prostatectomy for patients with recurrent prostate cancer is complex and failure rates are high, Jani explained. Conventional imaging has significant limitations and more accurate radiation therapy decision-making and treatment planning is needed.
“The study is unique,” he said, noting that randomized imaging studies with a cancer-control endpoint are rare. “But also, we had hardwired the post-PET treatment decisions into the protocol.”
In the investigational arm, patients received the following based on their PET results:
- Extra-pelvic uptake (no radiation)
- Pelvic uptake (45.0-50.4 Gy to the pelvis, 64.8-70.2 Gy to prostate bed)
- Prostate bed-only uptake (radiation to prostate bed)
- No uptake (radiation to prostate bed)
“The improved failure-free survival rate at 3 years is very impressive. [It’s] very hard to improve hard cancer endpoints to that degree,” said press briefing moderator Sue Yom, MD, of the University of California San Francisco.
“It’s important to understand the relationship between advanced imaging and advanced radiation,” she said. “The use of higher precision, image-guided therapies in radiation oncology offers the possibility of improving radiation planning and improving cancer control and symptoms in patients.”
Fluciclovine (18F) was approved in 2016 for use with PET imaging to help diagnose recurrence in men with treated prostate cancer and rising PSA levels, and is recommended by National Comprehensive Cancer Network guidelines. It binds to prostate-specific membrane antigen, a marker expressed by prostate cancer cells.
“But it is not used for radiation treatment planning,” said Yom. “So this study gives us data to make that case.”
From 2012 to 2019, EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement) randomized 165 patients with recurrent prostate adenocarcinoma post-prostatectomy 1:1 to radiotherapy based on standard imaging or radiotherapy based on standard imaging plus fluciclovine PET/CT.
In the study arm, findings on PET changed treatment planning in about 35% of cases, Jani noted.
For inclusion, patients needed a negative CT and bone scan, but detectable PSA, and were stratified by PSA levels (<2.0 vs ≥2.0 ng/mL), adverse pathology (positive margins, extracapsular extension, seminal vesicle invasion, or nodal involvement), and use of androgen deprivation therapy.
The study’s primary outcome was failure-free survival at 3 years, with treatment failure defined as persistent PSA, a PSA increase greater than 0.2 ng/mL from nadir plus a second increase, findings on imaging or rectal exam, or the start of systemic therapy.
Physician-assessed adverse events were similar between the two study arms, “suggesting that treatment to these PET-directed volumes was tolerable,” Jani said. In the control group, 3.7% had acute grade 3 genitourinary (GU) adverse events versus none in the PET-guided arm and there were no acute gastrointestinal (GI) toxicities in either. For late toxicities, 6.3% versus 6.7%, respectively, had grade 3 GU toxicities and none had late GI events.
“This is important, because I just presume that experimental imaging might detect more disease and cause the volumes of radiation to be larger, but that did not result in any negative impact to the patient,” said Yom.
Patient-reported toxicity will be reported at a later date.
Fluciclovine was invented at Emory, Jani noted. A follow-up study, EMPIRE-2, will test PET-guided radiotherapy with either fluciclovine or Ga-PSMA PET/CT.
The study was funded in part by a grant from the National Institutes of Health.
Jani works on an advisory board for Blue Earth Diagnostics.