PSMA-PET scans detect metastatic disease in 46% of patients with high-risk nonmetastatic hormone-sensitive prostate cancer, revealing understaging by conventional imaging.
Among patients with high-risk nonmetastatic hormone-sensitive prostate cancer, investigators found that these individuals were understaged by conventional imaging, according to findings from a post-hoc analysis published in JAMA Network Open, suggesting that some of these cases may be more advanced than initially expected.
In a study of patients with recurrent prostate cancer after radical prostatectomy, definitive radiotherapy or salvage radiotherapy, 182 individuals who were thought to not have metastasis were re-analyzed by investigators. Prostate-specific membrane antigen–positron emission tomography (PSMA-PET) scans detected cancer in 80% of patients after radical prostatectomy, 92% after initial radiation therapy, 85% after radical prostatectomy plus salvage radiation therapy and 84% of patients overall. The scans also revealed that 46% of patients had metastatic disease, with the highest rates seen in those who had radiation therapy first (56%) or surgery followed by salvage radiation (60%). Additionally, 24% of all patients had polymetastatic disease.
“We demonstrated that PSMA-PET detected metastatic disease in 46% of all patients, suggesting that a significant number of patients have disease that is understaged by conventional imaging,” first study author, Dr. Adrien Holzgreve, a visiting assistant professor at the David Geffen School of Medicine, University of California, Los Angeles (UCLA), UCLA Health, wrote.
“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,” he continued.
Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by rising prostate-specific antigen (PSA) levels in patients responsive to androgen deprivation therapy (ADT) but without detectable metastasis on conventional imaging. In the research published in JAMA Network Open, investigators aimed to better understand the utility of PSMA-PET compared with conventional imaging in a cohort of patients who met the inclusion criteria for the EMBARK trial, a phase 3 randomized study.
“We anticipated that PSMA-PET would detect more suspicious findings compared to conventional imaging. However, it was informative to uncover such a high number of metastatic findings in a well-defined cohort of patients resembling the EMBARK trial population that was supposed to only include those without metastases,” Holzgreve stated in an interview with UCLA Health, which was shared in a news release from the institution.
Understanding The Post-Hoc Analysis
Investigators screened 2,002 patients who were enrolled for treatment at UCLA Health, from September 15, 2016, to September 27, 2021, from four prospective study databases, thereby compiling a cohort of patients with high-risk nonmetastatic hormone-sensitive prostate cancer who had previously undergone PSMA-PET imaging for increasing PSA levels.
Enrolled patients had a median age of 69 years. The median PSA level before PSMA-PET imaging was 2.8 ng/mL, though this varied depending on prior treatment. These numbers were 2.4 ng/mL after radical prostatectomy, 6.9 ng/mL after radiation therapy as the initial treatment and 2.6 ng/mL after surgery followed by salvage radiation therapy.
Patients were eligible for enrollment so long as they had increasing PSA level above 1.0 ng/mL (after radical prostatectomy and salvage radiotherapy) or 2.0 ng/mL above the nadir value (after definitive radiotherapy), PSA doubling time of 9 months or less and serum testosterone level of 150 ng/dL or more; these criteria were reflective of the EMBARK trial criteria. Similarly, exclusion criteria for the investigation were reflective of EMBARK as well. Participants were not eligible for enrollment if they had distant metastatic disease detected by any conventional imaging, prior hormonal neoadjuvant or adjuvant therapy at the time of definitive radiotherapy for more than 36 months, more than 6 months of short-course ADT with less than 9 months of washout before randomization or advanced systemic therapy for prostate cancer.
From the electronic medical records as well as the existing databases from the previously listed prospective clinical trials, clinical characteristics including primary therapy, initial PSA, biopsy Gleason score, radical prostatectomy pathologic findings, ADT history, most recent PSA levels and PSA doubling times, were collected.
“PSMA-PET provides novel additional risk stratification for patients with [high-risk nonmetastatic hormone-sensitive prostate cancer] without distant metastasis based on conventional imaging. Further studies are needed to assess its potential independent prognostic value and its use for treatment guidance. Integration of PSMA-PET in major industry-sponsored clinical trials for secondary end points analyses is warranted,” the study authors concluded.
Reference:
“PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging” by Dr. Adrien Holzgreve, et al., JAMA Network Open.
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