3227 - Prognostic Value of Lesions with Low PSMA Uptake in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing PSMA-RLT
Presenter(s)
J. A. Benson1,2, D. Duenas1,2, L. Mao3, C. Kyriakopoulos4, A. V. Serritella4, R. Hutten1, S. Y. Cho5, and J. M. Floberg6; 1Department of Human Oncology, University of Wisconsin Hospitals and Clinics, Madison, WI, 2University of Wisconsin School of Medicine and Public Health, Madison, WI, 3Department of Biostatistics, University of Wisconsin School of Medicine and Public Health, Madison, WI, 4University of WIsconsin School of Medicine and Public Health, Department of Medicine, Division of Hematology/Oncology, Madison, WI, 5Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Department of Human Oncology, University of Wisconsin-Madison, Madison, WI
Purpose/Objective(s): Prostate specific membrane antigen (PSMA) radioligand therapy (RLT) improves survival in metastatic castration-resistant prostate cancer (mCRPC). PSMA expression measured by positron emission tomography (PET) using mean standardized uptake value (SUVmean) predicts response to PSMA-RLT. However, lesions with low PSMA uptake have the potential to drive resistance to PSMA-RLT, and this may not be captured by a patient-level metric like SUVmean. We hypothesized that pretreatment lesion-level PSMA-PET metrics predict response and survival following PSMA-RLT.
Materials/Methods: An IRB approved retrospective review was done on patients who underwent PSMA-RLT (n=49). All available PSMA-PET/CT scans were analyzed with a commercial software that identifies lesions and provides quantitative image metrics on a patient and individual lesion basis (AIQ Solutions, Madison, WI). Nine patients had this image analysis comparing pre and post treatment PET scans, which assigned lesions to 4 groups: increased (worsened), unchanged, decreased (improved), or disappeared. SUVmean and volume were collected from pretreatment PSMA-PET for all patients. The relationships of these markers to a 50% reduction in PSA (PSA50) and progression free survival (PFS) were investigated. Comparisons for lesion level response to treatment were done by Kruskal-Wallis and Wilcoxon rank-sum tests. Correlations between percent volume of lesions with specified SUVmean cutoffs and PSA50 were assessed with the Mann-Whitney U test and logistic regression. Survival analysis was performed with Cox regression and Kaplan-Meier analysis.
Results: In patients with pre- and post-treatment PSMA PET scans, lesions that increased had a significantly lower SUVmean compared to lesions that decreased (p=0.015). To determine if a subset of lesions drive progression, we compared the percent total volume of lesions with a low SUVmean to PSA50. The SUVmean range of all lesions was 0.8-30.0. Thresholds for SUVmean were determined from the group of lesions that increased in volume after treatment and included the median (3.6), mean (4.7), +½ standard deviation (SD) (6.3), and +1 SD (7.8). Patients who responded had a lower percentage of low SUVmean total lesion volume compared to non-responders (e.g. p<0.01 for SUVmean =6.3). Percent total lesion volume with a low SUVmean was correlated with PSA response (e.g. OR=0.98, 95% CI: 0.97-1.0 for SUVmean =6.3). Patients with =50% volume of lesions with an SUVmean =6.3 had worse PFS (140 vs 217 days; HR=1.93; 95% CI, 1.02–3.65).
Conclusion: Our findings demonstrated that lesions with a low SUVmean may drive progression for PSMA-RLT. PSMA PET imaging response demonstrated a significant difference in the SUVmean of lesions that increase in volume compared to those that decrease. Having a larger percentage of lesions with a low SUVmean correlated with lack of response and worse PFS. If identified pre-treatment, these low SUVmean lesions may be worth targeting with external beam radiation.