TY - JOUR
T1 - Quantitative 68Ga-PSMA-11 PET and Clinical Outcomes in Metastatic Castration-resistant Prostate Cancer Following 177Lu-PSMA-617 (VISION Trial)
AU - Kuo, Phillip H.
AU - Morris, Michael J.
AU - Hesterman, Jacob
AU - Kendi, A. Tuba
AU - Rahbar, Kambiz
AU - Wei, Xiao X.
AU - Fang, Bruno
AU - Adra, Nabil
AU - Garje, Rohan
AU - Michalski, Jeff M.
AU - Chi, Kim
AU - de Bono, Johann
AU - Fizazi, Karim
AU - Krause, Bernd
AU - Sartor, Oliver
AU - Tagawa, Scott T.
AU - Ghebremariam, Samson
AU - Brackman, Marcia
AU - Wong, Connie C.
AU - Catafau, Ana M.
AU - Benson, Taylor
AU - Armstrong, Andrew J.
AU - Herrmann, Ken
N1 - Publisher Copyright: © 2024 Radiological Society of North America Inc.. All rights reserved.
PY - 2024/8
Y1 - 2024/8
N2 - Background: Lutetium 177 [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Quantitative PSMA PET/CT analysis could provide information on 177Lu-PSMA-617 treatment benefits. Purpose: To explore the association between quantitative baseline gallium 68 [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT parameters and treatment response and outcomes in the VISION trial. Materials and Methods: This was an exploratory secondary analysis of the VISION trial. Eligible participants were randomized (June 2018 to October 2019) in a 2:1 ratio to 177Lu-PSMA-617 therapy (7.4 GBq every 6 weeks for up to six cycles) plus standard of care (SOC) or to SOC only. Baseline 68Ga-PSMA-11 PET parameters, including the mean and maximum standardized uptake value (SUVmeanand SUVmax), PSMA-positive tumor volume, and tumor load, were extracted from five anatomic regions and the whole body. Associations of quantitative PET parameters with radiographic progression-free survival (rPFS), overall survival (OS), objective response rate, and prostate-specific antigen response were investigated using univariable and multivariable analyses (with treatment as the only other covariate). Outcomes were assessed in subgroups based on SUVmeanquartiles. Results: Quantitative PET parameters were well balanced between study arms for the 826 participants included. The median wholebody tumor SUVmeanwas 7.6 (IQR, 5.8-9.9). Whole-body tumor SUVmeanwas the best predictor of 177Lu-PSMA-617 efficacy, with a hazard ratio (HR) range of 0.86-1.43 for all outcomes (all P < .001). A 1-unit whole-body tumor SUVmeanincrease was associated with a 12% and 10% decrease in risk of an rPFS event and death, respectively. 177Lu-PSMA-617 plus SOC prolonged rPFS and OS in all SUVmeanquartiles versus SOC only, with no identifiable optimum among participants receiving 177Lu-PSMA-617. Higher baseline PSMA-positive tumor volume and tumor load were associated with worse rPFS (HR range, 1.44-1.53 [P < .05] and 1.02-1.03 [P < .001], respectively) and OS (HR range, 1.36-2.12 [P < .006] and 1.04 [P < .001], respectively). Conclusion: Baseline 68Ga-PSMA-11 PET/CT whole-body tumor SUVmeanwas the best predictor of 177Lu-PSMA-617 efficacy in participants in the VISION trial. Improvements in rPFS and OS with 177Lu-PSMA-617 plus SOC were greater among participants with higher whole-body tumor SUVmean, with evidence for benefit at all SUVmeanlevels.
AB - Background: Lutetium 177 [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Quantitative PSMA PET/CT analysis could provide information on 177Lu-PSMA-617 treatment benefits. Purpose: To explore the association between quantitative baseline gallium 68 [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT parameters and treatment response and outcomes in the VISION trial. Materials and Methods: This was an exploratory secondary analysis of the VISION trial. Eligible participants were randomized (June 2018 to October 2019) in a 2:1 ratio to 177Lu-PSMA-617 therapy (7.4 GBq every 6 weeks for up to six cycles) plus standard of care (SOC) or to SOC only. Baseline 68Ga-PSMA-11 PET parameters, including the mean and maximum standardized uptake value (SUVmeanand SUVmax), PSMA-positive tumor volume, and tumor load, were extracted from five anatomic regions and the whole body. Associations of quantitative PET parameters with radiographic progression-free survival (rPFS), overall survival (OS), objective response rate, and prostate-specific antigen response were investigated using univariable and multivariable analyses (with treatment as the only other covariate). Outcomes were assessed in subgroups based on SUVmeanquartiles. Results: Quantitative PET parameters were well balanced between study arms for the 826 participants included. The median wholebody tumor SUVmeanwas 7.6 (IQR, 5.8-9.9). Whole-body tumor SUVmeanwas the best predictor of 177Lu-PSMA-617 efficacy, with a hazard ratio (HR) range of 0.86-1.43 for all outcomes (all P < .001). A 1-unit whole-body tumor SUVmeanincrease was associated with a 12% and 10% decrease in risk of an rPFS event and death, respectively. 177Lu-PSMA-617 plus SOC prolonged rPFS and OS in all SUVmeanquartiles versus SOC only, with no identifiable optimum among participants receiving 177Lu-PSMA-617. Higher baseline PSMA-positive tumor volume and tumor load were associated with worse rPFS (HR range, 1.44-1.53 [P < .05] and 1.02-1.03 [P < .001], respectively) and OS (HR range, 1.36-2.12 [P < .006] and 1.04 [P < .001], respectively). Conclusion: Baseline 68Ga-PSMA-11 PET/CT whole-body tumor SUVmeanwas the best predictor of 177Lu-PSMA-617 efficacy in participants in the VISION trial. Improvements in rPFS and OS with 177Lu-PSMA-617 plus SOC were greater among participants with higher whole-body tumor SUVmean, with evidence for benefit at all SUVmeanlevels.
UR - https://www.scopus.com/pages/publications/85201736991
UR - https://www.scopus.com/pages/publications/85201736991#tab=citedBy
U2 - 10.1148/radiol.233460
DO - 10.1148/radiol.233460
M3 - Article
C2 - 39162634
SN - 0033-8419
VL - 312
JO - Radiology
JF - Radiology
IS - 2
M1 - e233460
ER -