Katherine A Zukotynski, Urban Emmenegger1, Sebastien Hotte2, Anil Kapoor3, Wei Fu4, Amanda L Blackford4, John Valliant5, François Bénard6,7, Chun K Kim8, Mark C Markowski9, Mario A Eisenberger9, Emmanuel S Antonarakis9, Kenneth J Pienta10, Michael A Gorin, Matthew Lubanovic11, Jihyun Kim12, Martin G Pomper, Steve Y Cho12,13, Steven P Rowe. 1. Sunnybrook Odette Cancer Centre and Research Institute, University of Toronto, Toronto, Ontario, Canada. 2. Department of Oncology, McMaster University, Hamilton, Ontario, Canada. 3. Department of Urology, McMaster University, Hamilton, Ontario, Canada. 4. Division of Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. 5. Department of Chemistry, McMaster University, Hamilton, Ontario, Canada. 6. Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada. 7. PET Functional Imaging, BC Cancer, Vancouver, British Columbia, Canada. 8. Department of Medicine, Hanyang University College of Medicine, Seoul, South Korea. 9. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. 10. James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 11. Departments of Radiology and Medicine, McMaster University, Hamilton, Ontario, Canada. 12. Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; and. 13. University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
Abstract
PET with small molecules targeting prostate-specific membrane antigen (PSMA) is being adopted as a clinical standard for prostate cancer imaging. In this study, we evaluated changes in uptake on PSMA-targeted PET in men starting abiraterone or enzalutamide. Methods: This prospective, single-arm, 2-center, exploratory clinical trial enrolled men with metastatic castration-resistant prostate cancer initiating abiraterone or enzalutamide. Each patient was imaged with 18F-DCFPyL at baseline and within 2-4 mo after starting therapy. Patients were followed for up to 48 mo from enrollment. A central review evaluated baseline and follow-up PET scans, recording change in SUVmax at all disease sites and classifying the pattern of change. Two parameters were derived: the δ-percent SUVmax (DPSM) of all lesions and the δ-absolute SUVmax (DASM) of all lesions. Kaplan-Meier curves were used to estimate time to therapy change (TTTC) and overall survival (OS). Results: Sixteen evaluable patients were accrued to the study. Median TTTC was 9.6 mo (95% CI, 6.9-14.2), and median OS was 28.6 mo (95% CI, 18.3-not available [NA]). Patients with a mixed-but-predominantly-increased pattern of radiotracer uptake had a shorter TTTC and OS. Men with a low DPSM had a median TTTC of 12.2 mo (95% CI, 11.3-NA) and a median OS of 37.2 mo (95% CI, 28.9-NA), whereas those with a high DPSM had a median TTTC of 6.5 mo (95% CI, 4.6-NA, P = 0.0001) and a median OS of 17.8 mo (95% CI, 13.9-NA, P = 0.02). Men with a low DASM had a median TTTC of 12.2 mo (95% CI, 11.3-NA) and a median OS of NA (95% CI, 37.2 mo-NA), whereas those with a high DASM had a median TTTC of 6.9 mo (95% CI, 6.1-NA, P = 0.003) and a median OS of 17.8 mo (95% CI, 13.9-NA, P = 0.002). Conclusion: Findings on PSMA-targeted PET 2-4 mo after initiation of abiraterone or enzalutamide are associated with TTTC and OS. Development of new lesions or increasing intensity of radiotracer uptake at sites of baseline disease are poor prognostic findings suggesting shorter TTTC and OS.
PET with small molecules targeting prostate-specific membrane antigen (PSMA) is being adopted as a clinical standard for prostate cancer imaging. In this study, we evaluated changes in uptake on PSMA-targeted PET in men starting abiraterone or enzalutamide. Methods: This prospective, single-arm, 2-center, exploratory clinical trial enrolled men with metastatic castration-resistant prostate cancer initiating abiraterone or enzalutamide. Each patient was imaged with 18F-DCFPyL at baseline and within 2-4 mo after starting therapy. Patients were followed for up to 48 mo from enrollment. A central review evaluated baseline and follow-up PET scans, recording change in SUVmax at all disease sites and classifying the pattern of change. Two parameters were derived: the δ-percent SUVmax (DPSM) of all lesions and the δ-absolute SUVmax (DASM) of all lesions. Kaplan-Meier curves were used to estimate time to therapy change (TTTC) and overall survival (OS). Results: Sixteen evaluable patients were accrued to the study. Median TTTC was 9.6 mo (95% CI, 6.9-14.2), and median OS was 28.6 mo (95% CI, 18.3-not available [NA]). Patients with a mixed-but-predominantly-increased pattern of radiotracer uptake had a shorter TTTC and OS. Men with a low DPSM had a median TTTC of 12.2 mo (95% CI, 11.3-NA) and a median OS of 37.2 mo (95% CI, 28.9-NA), whereas those with a high DPSM had a median TTTC of 6.5 mo (95% CI, 4.6-NA, P = 0.0001) and a median OS of 17.8 mo (95% CI, 13.9-NA, P = 0.02). Men with a low DASM had a median TTTC of 12.2 mo (95% CI, 11.3-NA) and a median OS of NA (95% CI, 37.2 mo-NA), whereas those with a high DASM had a median TTTC of 6.9 mo (95% CI, 6.1-NA, P = 0.003) and a median OS of 17.8 mo (95% CI, 13.9-NA, P = 0.002). Conclusion: Findings on PSMA-targeted PET 2-4 mo after initiation of abiraterone or enzalutamide are associated with TTTC and OS. Development of new lesions or increasing intensity of radiotracer uptake at sites of baseline disease are poor prognostic findings suggesting shorter TTTC and OS.
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