PSMA-dRT Trial Update: Evaluating PSMA PET/CT for Improved Staging, Treatment Planning in Prostate Cancer

A recent update from the PSMA-dRT trial highlights the potential benefits of using prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging for patients with unfavorable intermediate- or high-risk prostate cancer undergoing definitive radiation therapy (dRT). The trial aimed to determine whether PSMA PET/CT could enhance treatment planning and improve patient outcomes compared with conventional imaging methods. Lead author John Nikitas, MD, of the Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, in Los Angeles, California, will present the results at the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting.

PSMA PET/CT is recognized for its superior diagnostic accuracy in detecting regional and distant metastases in prostate cancer compared with conventional imaging techniques like CT, bone scans, and magnetic resonance imaging. This advanced imaging method has the potential to significantly refine patient selection and planning for dRT, but its impact on patient outcomes needs validation through clinical trials.

PSMA-dRT was a multi-institutional, randomized, phase 3 clinical trial designed to assess the impact of PSMA PET/CT on treatment outcomes for patients with prostate cancer. The study planned to randomize 312 men with unfavorable intermediate- or high-risk prostate cancer in a 1.08:1.00 ratio to receive either a PSMA PET/CT scan before starting dRT (n=162) or proceed without it (n=150). Treating radiation oncologists incorporated PSMA PET/CT findings into their radiation therapy planning for the intervention group, while the control group used other imaging modalities. The primary end point was 5-year progression-free survival (PFS).

The trial had to close early in February 2022, following the US Food and Drug Administration’s approval and insurance coverage of PSMA PET/CT scans. This change made it unacceptable for many patients and physicians to proceed without PSMA PET in the control group. Between November 2020 and December 2021, 54 patients were randomized, with 25 in the PSMA PET/CT arm and 29 in the control arm.

PSMA PET/CT upstaged 17% of patients compared with prior baseline staging, leading to more accurate treatment planning. Among the patients in the PSMA PET/CT arm, 14 (58.3%) had localized disease, 6 (25.0%) had locally advanced disease, 3 (12.5%) had regional metastasis, and 1 (4.2%) had nodal and distant metastases. All patients with regional metastasis received pelvic lymph node irradiation, and the patient with distant metastases received a combination of androgen deprivation therapy, abiraterone acetate, prednisone, and consolidative radiotherapy.

At a median follow-up of 21 months, no cases of biochemical failure, radiographic or biopsy-proven recurrence, salvage therapy, or prostate-cancer death were observed in either arm. Two-year PFS was 93.8% in the PSMA PET/CT arm and 100% in the control arm, with no significant difference in PFS between the 2 arms (P=.13). There were 2 non-prostate cancer deaths in the PSMA PET/CT arm.

The PSMA-dRT trial highlights the value of PSMA PET/CT in enhancing staging accuracy and treatment planning for patients with prostate cancer. The findings suggest that PSMA PET/CT is a valuable tool in the management of prostate cancer, warranting further investigation in larger, adequately powered studies.