Treatment Based on Advanced Molecular Imaging Can Improve DFS in Prostate Cancer

The use of advanced molecular imaging with the PET radiotracer fluciclovine (¹⁸F) to inform treatment decisions can lead to improved disease-free survival (DFS) rates in patients with recurrent prostate cancer, according to data from the phase 2/3 EMPIRE-1 (NCT01666808) trial presented during the 2020 American Society for Radiation Oncology Annual Meeting.^1,2

Results showed that at 3 years, the failure-free survival rate in patients with prostate cancer and detectable prostate-specific antigen (PSA) following prostatectomy who received treatment that was finalized based on PET imaging with fluciclovine was 75.5% versus 63.0% in those who received radiation therapy based on conventional imaging (P =.003); this translated to a 12% difference between the arms. At 4 years, these rates were 75.5% and 51.2%, respectively (P <.001).

“At 3 years, we did find that the group getting the PET scan had a better cancer control rate…and this persisted at 4 years,” Ashesh B. Jani, MD, MSEE, FASTRO, radiation oncologist and prostate cancer specialist at Winship Cancer Institute of Emory University stated in a recap. “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.”

The major goal of the trial was to evaluate the use of advanced molecular imaging in an attempt to better guide decision making following prostatectomy, specifically with regard to radiation therapy.

From 2012 to 2019, patients were stratified by PSA (less than 2.0 ng/mL vs 2.0 ng/mL or more), adverse pathology (extracapsular extension, positive seminal vesicle, positive margin, positive node; none vs any), and androgen deprivation therapy (ADT) use (yes vs no). Participants were randomized to have radiation therapy decision making and delivery in accordance with the usual routine per conventional imaging (arm 1) or radiation therapy decision and volumes guided by PET imaging with fluciclovine (arm 2).

In arm 2, the decisions were rigidly determined by PET imaging. If there was extra-pelvic uptake, no radiation therapy was recommended; pelvic uptake dictated radiation to the pelvis of 45.0 Gy to 50.4 Gy and the prostate bed of 64.8 Gy to 70.2 Gy; prostate bed–only uptake called for radiation to the prostate bed; and no uptake dictated radiation to the prostate bed. In this arm, PET was also registered with planning CT for target delineation.

Kaplan-Meier curves were produced 4 years after radiation treatment was completed and the curves were compared using the logrank test. Moreover, the Z test was used to compare the failure rates at 3 years versus 4 years. Univariate and multivariable analyses were done for demographic, disease, and treatment factors.

A total of 165 patients were enrolled to EMPIRE-1; 82 patients comprised arm 1, while 83 patients comprised arm 2. Both treatment arms were well balanced with regard to age, race, PSA, Gleason score, extracapsular extension, seminal vesicle, positive margin, positive node, and ADT use.

One patient in arm 1 withdrew before radiation therapy; 3 patients in arm 2 withdrew before radiation therapy and 1 was not able to undergo PET imaging although this patient received radiation. PET uptake in arm 2 (n = 79) was as follows: extra-pelvic (n = 4), pelvic plus or minus prostate bed (n = 27), prostate bed only (n = 32), and none (n = 16). This imaging led to a 35.4% rate of decision changes; 4 patients stopped radiation treatment. In those undergoing radiation therapy (arm 1: n = 81; arm 2: n = 76), the median follow-up was 2.48 years; 125 patients had a minimum follow-up of 3 years.

Results from the multivariate analysis showed that arm (HR, 2.04; 95% CI, 1.06-3.93; P =.033), extracapsular extension (P =.035), pelvic field (P =.031), and PSA (P <.001) were determined to reach statistical significance. Moreover, toxicity was found to be comparable between the 2 treatment arms, which indicates that PET-guided therapeutic decisions were well tolerated.

“Fluciclovine was developed at Emory by Mark M. Goodman, PhD, and this is a synthetic amino acid, a PET radio tracer. An amino acid transport is upregulated in many cancers, including prostate cancer, and we took advantage of that to increase the sensitivity of imaging to recurrent disease,” said David M. Schuster, MD, FACR. “We knew that the diagnostic performance of the PET radio tracer was better than conventional imaging. We also know that it changes management in the right direction and this study has allowed us to take imaging one step further and determine if by using the imaging, we have influenced outcomes for the better. And we have.”

Another trial, EMPIRE-2 (NCT03762769) has been launched to evaluate a newer type of advanced molecular imaging, a prostate-specific membrane antigen PET radiotracer which targets a receptor on the surface of prostate cancer cells.

References

1. Jani A, Schreibmann E, Goyal S, et al. Initial report of a randomized trial comparing conventional- vs conventional plus fluciclovine (18F) PET/CT imaging-guided post-prostatectomy radiotherapy for prostate cancer. Presented at: 2020 American Society for Radiation Oncology Annual Meeting; October 24-27, 2020; Virtual. Abstract LBA 1. https://bit.ly/2HK6xhI.

2. Winship study shows increased failure-free survival in prostate cancer. News release. Winship Cancer Institute. October 23, 2020. Accessed October 28, 2020. https://bit.ly/2TuUVlA.