Prostate-specific membrane antigen positron emission tomography (PSMA PET) offers significantly different insight than conventional imaging into the metastatic spread of high-risk, hormone sensitive prostate cancer, according to newly published research.
For the retrospective cross-sectional study, recently published in JAMA Network Open, researchers reviewed PSMA PET data for 182 patients with high-risk, hormone-sensitive prostate cancer (PCa). Drawn from four prospective studies, the cohort had been deemed eligible for inclusion for a randomized, phase 3 study (EMBARK) of enzalutamide (Xtandi, Astellas Pharma/Pfizer) in the treatment of men with high-risk non-metastatic prostate cancer.
The cohort was comprised of patients (median age of 69) who had recurrent prostate cancer (PCa) after undergoing radical prostatectomy (RP), definitive radiotherapy (dRT) or salvage radiotherapy (SRT). In addition to increasing prostate-specific antigen (PSA) levels (greater than 1 ng/mL after RP and SRT, and 2 ng/mL above the nadir value after dRT), all patients had a PSA doubling time of nine months or less, and a serum testosterone level > 150 nd/dL, according to the study.
While conventional imaging revealed no evidence of metastatic disease in this patient cohort, the study authors found that PSMA PET demonstrated polymetastatic disease in 24 percent of patients and M1 disease staging in 46 percent of patients. The researchers noted that 84 percent of the cohort had positive PSMA PET results.
“ … We demonstrated that PSMA-PET detected metastatic disease in 46% of all patients, suggesting that a significant number of patients have disease that is under-staged by conventional imaging.,” noted lead study author Adrien Holzgreve, M.D., who is affiliated with the Ahmanson Translational Theranostics Division in the Department of Molecular and Medical Pharmacology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), and colleagues.
(Editor’s note: For additional content on prostate cancer imaging, click here.)
Specifically, the study authors noted that 80 percent of patients who had RP demonstrated positive PSMA PET findings after the procedure. Ninety-two percent of dRT-treated patients had PCa recurrence on PSMA PET and 85 percent of men had positive PSMA PET finding after undergoing RP and SRT, according to the researchers.
Other PSMA PET findings revealed pelvic nodal disease in 29 percent of the cohort with 40 percent occurring in RP-treated patients, 23 percent in patients who had RP and SRT, and 13 percent in dRT-treated patients.
Three Key Takeaways
1. Improved metastatic detection. PSMA PET imaging identified metastatic disease in 46 percent of patients with high-risk, hormone-sensitive prostate cancer compared to conventional imaging, which detected no metastatic disease in the same cohort. This highlights the superior sensitivity of PSMA PET in staging.
2. Clinical implications for staging and treatment. The findings suggest that a significant number of prostate cancer cases are under-staged by conventional imaging methods, potentially impacting treatment decisions and patient outcomes. PSMA PET may play a critical role in selecting patients for clinical trials and interventions.
3. Detection of nodal and distant metastases. PSMA PET identified pelvic nodal disease in 29 percent of patients and distant metastases in 60 percent of those treated with RP and SRT, 56 percent with dRT, and 34 percent with RP alone, demonstrating its effectiveness in detecting both regional and distant disease.
The researchers said PSMA PET-detected distant metastatic disease in 60 percent of patients who had RP and SRT, 56 percent of those treated with dRT and 34 percent of men who had RP only.
“The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” emphasized Holzgreve and colleagues.
(Editor’s note: For related content, see “The Role of PSMA PET in Early Detection and Prostate Cancer Staging,” “Systematic Review: PET/MRI May be More Advantageous than PET/CT in Cancer Imaging” and “Study: PSMA PET/CT More Advantageous than MRI for Locoregional Staging of Prostate Cancer.”)
In regard to study limitations, the authors acknowledged that the cohort had more patients who had radical prostatectomy alone and fewer patients who had salvage radiotherapy in comparison to the EMBARK trial. The researchers noted a lack of longitudinal follow-up and conceded that false-positive findings of metastasis can occur with the use of PSMA PET in the staging of PCa.
