PSMA PET/CT May Have Major Impact on Treatment of Patients With Prostate Cancer
Prostate cancer experts speaking at the 2020 Genitourinary Cancers Symposium alluded to the fact that prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) scanning is more sensitive than conventional imaging for the detection of occult lesions in men with prostate cancer. The fact that PSMA PET/CT scans detect more cancerous lesions compared with conventional imaging is not controversial, and many experts think this is the wave of the future.
But the most important question is the clinical utility of this modality: will its use change practice? One of the largest studies to date, presented at the Symposium during a poster session, showed that the use of PSMA PET/CT did in fact change management in 40% to 67% of patients, depending on the scenario.1
“These results are extremely encouraging. PSMA PET/CT detects more disease than widely used PET radiotracers for prostate cancer….”— Ida Sonni, MD
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“PSMA PET/CT significantly impacted the stage and management of patients with prostate cancer across various clinical scenarios. Its utility goes beyond the two classic clinical applications of biochemical recurrence and presurgical staging,” said Ida Sonni, MD, of the David Geffen School of Medicine, University of California, Los Angeles (UCLA).
“These results are extremely encouraging. PSMA PET/CT detects more disease than widely used PET radiotracers for prostate cancer, such as choline PET and the U.S. Food and Drug Administration–approved 18F-fluciclovine–PET,” she added.
“The majority of published studies with PSMA PET/CT report results in two main indications: biochemical recurrence after definitive therapy defined by prostate-specific antigen (PSA) criteria and presurgical staging. In this study, we included patients who have undergone PSMA PET/CT outside these two indications. This was a heterogeneous population that included patients with known metastatic or advanced castration-resistant disease, treated with nonconventional primary therapies—for example, high-intensity focused ultrasound, focal laser ablation, cryoablation, hyperthermia, or irreversible electroporation, or biochemical recurrence not yet meeting the PSA criteria (for example, PSA < 0.2 ng/mL),” Dr. Sunni explained.
The goal of this prospective basket study was to determine whether the use of PSMA PET/CT would change management in patients not typically included in trials of PSMA PET/CT. Secondary objectives were to evaluate changes in stage and detection rate stratified by PSA and clinical indication and to stratify changes in management by clinical indication. The study included 234 patients with prostate cancer enrolled between April 2018 and January 2019; 197 were included in the final analysis. A total of 37 patients were excluded for various reasons. Referring treating physicians were sent questionnaires before PSMA PET/CT, immediately after imaging, and a few months later.
The detection rate varied significantly among subgroups (P < .001) and was lowest in the restaging postsurgery subgroup (8%). The pre-PET stage as determined by referring physicians changed after PSMA PET/CT in 69% of patients. PSMA PET/CT upstaged 38% of patients, downstaged 30%, and had no effect on staging in 32%.
- One of the largest studies to date on patients with prostate cancer undergoing PSMA PET/CT imaging (outside the two main indications of biochemical recurrence after definitive therapy and initial staging) shows that it has a large impact on staging and management in a variety of clinical scenarios.
- Patients who seem to benefit the most had restaging scans post-radiation before PSA levels reached the Phoenix criteria for the definition of biochemical recurrence.
- Patients who seem to benefit the least were those who were scanned after surgery and who had very low–burden disease.
- Randomized trials are needed to demonstrate the best use of PSMA PET/CT.
“Results had a high impact on management and confidence in the therapeutic approach,” Dr. Sonni noted. “Disease stage was changed in 86% of patients post–radiation therapy, and management changed in 72%. These patients—those who did not yet meet the Phoenix criteria for biochemical recurrence—seemed to benefit the most from imaging.”
Overall, management was changed in 57% of patients based on PSMA PET/CT findings and was unchanged in 43%. Broken down by subgroup, changes in management were as follows: initial staging in treatment-naive patients, 67%; restaging post–androgen-deprivation therapy, 81%; restaging postsurgery, 38%; restaging postirradiation without meeting the criteria for biochemical recurrence (PSA nadir < 2 ng/mL), 72%; restaging after other primary treatment, 67%; and restaging advanced disease, 61%. The most common changes in management in the full cohort were the conversion from systemic to focal treatment (16%) and changes in focal treatment (10%). “This finding highlights the fact that lesion detection can lead to focal treatment targeted to metastases. Whether this approach will affect patient outcomes needs to be determined in future prospective studies,” she said.
The impact on patient stage was lowest (38%) in patients restaged after surgery with PSA levels ≤ 0.2 ng/mL. However, management changes were still implemented in 46% of those patients. Although this was a small group of 13 patients, “these findings suggest that this population with early-stage disease and very low tumor burden may not benefit as significantly from PSMA PET/CT,” she said.
“I’ve personally never spoken with a clinician who did not believe in PSMA PET/CT. In certain clinical scenarios I think this imaging will replace conventional imaging eventually. You can have a negative bone scan and see multiple metastases on PSMA PET/CT,” Dr. Sonni told The ASCO Post. There are different types of PSMA scans with slightly different characteristics and radiotracers. The UCLA researchers used PSMA-11 radiolabeled with gallium-68.
Old Imaging Techniques Obsolete?
Acknowledging that PSMA PET/CT was the wave of the future, Celestia S. “Tia” Higano, MD, FACP, of Seattle Cancer Care Alliance Hospital at the University of Washington Medical Center, said: “I don’t feel comfortable yet throwing away traditional scans, such as bone and pelvic scans. I wouldn’t rely solely on newer techniques yet. Not that PSMA PET/CT isn’t highly specific, but we don’t have enough experience with it to know how it translates to clinical management in the absence of conventional imaging results.”
Celestia S. “Tia” Higano, MD, FACP
She added: “I don’t know what to make of a PSMA PET/CT scan that shows five lesions [outside the definition of oligometastatic disease] without a bone scan and a CT scan. This still may be very low–volume disease if not detected by conventional imaging or if disease is detected by conventional imaging, it may well be in the “high-volume” category,” she continued. “I am more interested in obtaining PSMA PET/CT in a situation where standard imaging is negative in the presence of a positive PSMA PET/CT,” she stated. “At present, I use conventional imaging and if it is positive, treat accordingly, but if negative, I will proceed with molecular imaging (18F-fluciclovine–PET and/or PSMA PET) to help determine treatment options.”
DISCLOSURE: Dr. Sonni reported no conflicts of interest. Dr. Higano has received honoraria from Astellas Pharma; has served in a consulting or advisory role for AstraZeneca, Bayer, Blue Earth Diagnostics, Carrick Therapeutics, Clovis Oncology, Ferring, Hinova, Janssen, Merck Sharp & Dohme, Novartis, and Pfizer; has received institutional research funding from Aragon Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Effector Therapeutics, Emergent BioSolutions, Ferring Pharmaceuticals, Medivation, Pfizer, and Roche; and has been reimbursed for travel, accommodations, or other expenses by Bayer, Blue Earth Diagnostics, Carrick Therapeutics, Clovis Oncology, Ferring, Hinova Pharmaceuticals, Janssen Oncology, Merck Sharp & Dohme, Novartis, and Pfizer.
1. Sonni I, Eiber M, Fendler W, et al: Impact of 68Ga-PSMA PET/CT on staging and management of prostate cancer patients in various clinical settings. 2020 Genitourinary Cancers Symposium. Abstract 26. Presented February 13, 2020.
“This is a great study. It is one of the largest series of prostate-specific membrane antigen (PSMA) scans and covers many patient scenarios, including initial staging, restaging after surgery or radiation or hormonal therapy, and re-imaging in advanced disease,” said Charles G. Drake, MD, PhD, a...