PSMA-PET Scanning Wave of the Future in Prostate Cancer

Positron emission tomography (PET) scanning targeted to detect prostate-specific membrane antigen (PSMA) is poised to overtake conventional imaging, according to presentations at the 2020 Genitourinary Cancers Symposium.

Two studies add further support for the value of PSMA-PET. One study clearly demonstrates that PSMA-PET detects prostate cancers missed on conventional imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI). A second study showed that PSMA-PET findings changed the management of prostate cancer in 40% to 67% of patients, depending on the scenario.

Phase 2/3 OSPREY Study

PSMA-PET testing detected lymph node or distant metastases that were missed by CT or MRI in >25% of men with high-risk prostate cancer in the prospective, multicenter OSPREY study. The perceived value of PSMA-PET is that more accurate staging of disease will affect treatment selection.

At study entry, conventional imaging with pelvic CT or MRI showed no evidence of regional or distant metastases in 96% to 97% of the 268 enrolled patients. The biopsy-confirmed results showed that 72 (27%) of the patients had disease that had spread beyond the prostate. Of these patients, almost 15% had locally advanced disease and 12% had distant metastases.

18F-DCFPyL PET/CT had sensitivity of 31% to 42% and specificity of 96% to 99%. The sensitivity increased to 63% with no loss of specificity when small lymph nodes known to be below the PET detection limit were excluded.

“In men with high-risk prostate cancer who are candidates for radical prostatectomy and pelvic lymph node dissection, PET/CT with 18F-DCFPyL improved clinical N and M staging, despite completely blinded image reads,” stated Frédéric Pouliot, MD, PhD, FRCSC, Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec City, Canada.

“Significant clinical information that was gained with 18F-DCFPyL PET imaging is likely to directly impact patient management,” he added.

PSMA is overexpressed in 94% of prostate cancers. In this study, 18F-DCFPyL was used as a radiotracer. Other radiotracers have selective high-affinity binding to PSMA, such as gallium or lutetium. Many of these tracers have not yet been evaluated in prospective, multicenter controlled trials, Dr Pouliot noted.

Dr Pouliot reported data based on findings from a cohort of 268 patients with newly diagnosed, high-risk prostate cancer who were enrolled in the phase 2/3 OSPREY trial, which had 3 central, independent PSMA PET/CT readers and 1 central reader for conventional imaging, all of which were blinded to the clinical and imaging results.

Of these patients, 252 (median age, 64 years) had evaluable ­DCFPyL PET/CT imaging results and pathologic findings from prostatectomy and pelvic lymph node dissection. The primary end points were specificity and sensitivity within the pelvic lymph nodes. The median prostate-specific antigen (PSA) level was 9.3 ng/mL.

The positive and negative predictive values (secondary end points) of PSMA-­PET ranged from 78.1% to 90.5% and 81.4% to 83.8%, respectively, across the 3 readers.

How Is PSMA-PET Being Used?

PSMA-PET can detect more prostate cancer cells than conventional imaging, but the question is whether these findings will change patient management.

One of the largest prospective studies of PSMA-PET to date showed that the findings changed the management of prostate cancer in 40% to 67% of patients, depending on the patient’s scenario. Moreover, the results suggest that PSMA-PET can provide useful information beyond the 2 classical clinical indications for which it has been studied thus far—biochemical recurrence after definitive treatment and presurgical staging.

“These results are extremely encouraging. PSMA-PET has better results than choline PET and FDG-PET in detecting more disease. We included patients in this study who have not been analyzed using PSMA-PET/CT,” said Ida Sonni, MD, Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, who discussed the second study.

“This was a heterogeneous group that included advanced nonmetastatic disease, primary treatment with novel agents, treatment with surgery and radiation before biochemical recurrence, and those with primary treatments other than radiation and surgery, for example, high-intensity focused ultrasound, focal laser ablation, cryoablation, hyperthermia, or irreversible electroporation,” she added.

The study included 234 patients with prostate cancer who were enrolled between April 2018 and January 2019; 197 patients were included in the final analysis, and 37 patients were excluded for various reasons. Physicians were sent questionnaires before imaging, immediately after imaging, and a few months later.

The detection rate varied significantly (P <.001) among the subgroups and was lowest in the restaging postsurgery subgroup (8%). The pre-PET stage, as determined by referring physicians, changed after PSMA-PET in 69% of patients. PSMA-PET upstaged 38% of patients, downstaged 30% of patients, and had no effect on staging in 32% of patients.

Overall, the management was changed in 57% of the patients, based on the PSMA-PET findings and was unchanged in 43% of patients.

In this study, the patients who benefited the most from PSMA-­PET were evaluated after radiation and did not have biochemical recurrence; the disease stage changed in 86% of these patients, and the management changed in 72%. Patients who benefited the least from PSMA-­PET were evaluated postsurgery and had no evidence of biochemical recurrence; the disease stage changed in 38% of these patients and the management changed in 46%.

The changes in disease management in each category were 67% in the initial staging of treatment-naïve patients, 81% in restaging after androgen-deprivation therapy, 38% in restaging after surgery, 72% in restaging after radiation without meeting the criteria for biochemical recurrence (PSA nadir <2), 61% in restaging after receiving other primary treatment, and 61% in restaging with advanced disease.

The most common changes of treatment in the full cohort were the conversion from systemic to focal treatment (16%) and changes in focal treatment (10%).

“This finding highlights that high 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,” Dr Sonni said.

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