Emerging data suggest that metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease, and PSMA response has been proposed as a biomarker for treatment response. Herein, we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC.
We performed an international multi-institutional retrospective study of patients with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation who underwent PSMA-PET/computed tomography (CT) before and after (median, 6.2 months; range, 2.4-10.9 months) treatment. Pre- and post-MDT PSMA-PET/CT maximum standardized uptake value (SUVmax) was measured for all lesions, and PSMA response was defined as the percent change in SUVmax of the least responsive lesion. PSMA response was both evaluated as a continuous variable and dichotomized into PSMA responders, with a complete/partial response (at least a 30% reduction in SUVmax), and PSMA nonresponders, with stable/progressive disease (less than a 30% reduction in SUVmax). PSMA response was correlated with conventional imaging-defined metastasis-free survival (MFS) via Kaplan-Meier and Cox regression analysis.
A total of 131 patients with 261 treated metastases were included in the analysis, with a median follow-up of 29 months (IQR, 18.5-41.3 months). After stereotactic ablative radiation, 70.2% of patients were classified as PSMA responders. Multivariable analysis demonstrated that PSMA response as a continuous variable was associated with a significantly worse MFS (hazard ratio = 1.003; 95% CI, 1.001-1.006; P = .016). Patients classified as PSMA responders were found to have a significantly improved median MFS of 39.9 versus 12 months (P = .001) compared with PSMA nonresponders. Our study is limited as it is a retrospective review of a heterogenous population.
After stereotactic ablative radiation, PSMA-PET response appears to be a radiographic biomarker that correlates with MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated in a prospective setting.
Advances in radiation oncology. 2024 Apr 13*** epublish ***
Philip Sutera, Matthew P Deek, Rebecca A Deek, Ozan Cem Guler, Pervin Hurmuz, Mehmet Reyhan, Steven Rowe, Noura Radwan, Shirl Dipasquale, William T Hrinivich, Kathryn Lowe, Lei Ren, Biren Saraiya, Ronald Ennis, Lara Hathout, Tina Mayer, Theodore L Deweese, Daniel Y Song, Ana Kiess, Ezgi Oymak, Kenneth Pienta, Felix Feng, Martin Pomper, Gokhan Ozyigit, Phuoc T Tran, Cem Onal, Ryan M Phillips
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey., Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana Dr Turgut Noyan Research and Treatment Center, Adana, Turkey., Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey., Department of Nuclear Medicine, Faculty of Medicine, Baskent University, Adana Dr Turgut Noyan Research and Treatment Center, Adana, Turkey., The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland., Department of Radiation Oncology, University of Maryland, Baltimore, Maryland., Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey., Division of Radiation Oncology, Iskenderun Gelisim Hospital, Hatay, Turkey., Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland., Department of Radiation Oncology, University of California San Francisco, San Francisco, California., Department of Radiation Oncology, The Mayo Clinic, Rochester, Minnesota.