Efficacy of 68Ga-PSMA PET/CT-derived whole-body volumetric parameters in predicting response to second-generation androgen receptor axis-targeted therapy, and the prognosis in metastatic hormone-refractory prostate cancer patients

Abstract

IntroductionThe present study investigates the role of 68 Ga-PSMA PET/CT-derived whole-body metabolic and volumetric parameters in the prediction of treatment response and prognosis among metastatic hormonerefractory prostate cancer patients undergoing secondgeneration androgen receptor axis-targeted therapy (abiraterone or enzalutamide). Materials and methodsThis retrospective study included 44 metastatic hormone-refractory prostate cancer patients undergoing 68 Ga-PSMA PET/CT, including 29 enzalutamide-treated and 15 abiraterone-treated patients. ResultsOf the 44 patients included in the study, 29 received enzalutamide and 15 received abiraterone. During treatment, the changes in PET parameters were correlated with the PSA (biochemical) response. More specifically, a positive correlation was noted between PSA response and percent change in TLP (∆TLP) response, and there was concordance between the results (r = 0.652, k = 0.42, P < 0.001). Baseline PSA (P =0.05), high MTVw (P = 0.005), the increase in ∆PSA (P = 0.036), ∆TLP (P = 0.039) and percent change in MTV (∆MTV) (P = 0.049) values were identified as factors associated with mortality risk.Multivariate analysis showed that PSA1 [odds ratio (OR): 1.005, 95% confidence interval (CI) 1.002-1.008, P = 0.004], ∆PSA (OR: 14.7, 95% CI 1.50-143.7, P = 0.02) and MTVw1 (OR: 11.4,6, P = 0.04) were independent prognostic factors associated with mortality risk. ConclusionA statistically significant concordance and correlation was noted between 68 Ga-PSMA PET/ CT-derived whole-body metabolic parameters (∆TLP and ∆MTV) and ∆PSA. In addition, the baseline PSA, ∆PSA, ∆TLP, ∆MTV and TMTV were identified as predictive factors for mortality risk.

Associations of quantitative whole-body PSMA-PET metrics with PSA progression status under long-term androgen deprivation therapy in prostate cancer patients: a retrospective single-center study

“…In this analysis, percent changes in PSA were correlated with percent changes in WB-PSMA-VOL and WB-PSMA-SUV mean , suggesting that changes in quantitative PSMA-PET metrics may be predictive of clinical response. These findings are consistent with another retrospective analysis of 44 mCRPC patients, which found a concordance between changes in WB-PSMA-PET derived parameters and changes in PSA (Oruc et al 2021 ). Our analysis also shows that patients who were upstaged by miTNM staging on PET2 were more likely to experience PSA progression on PET2, suggesting that miTNM staging using PROMISE criteria is associated with conventional response criteria.…”

Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH)

“…In rationalising the use of choline and PSMA PET, it is appreciated that PSMA expression is inversely related to androgen response; androgen deprivation, or abiraterone treatment of human castration-resistant PCa cell line VCaP-stimulated PSMA expression and increased PSMA-based radiotracer uptake [41]. On the other hand, a loss of cell viability will be expected to decrease radiotracer uptake; thus, while human studies with PSMA-PET to monitor therapy response following arbiraterone or enzalutamide have been reported [37,42], the interpretation of the data is challenging [38].…”

Gallium-68 Prostate-Specific Membrane Antigen Positron Emission Tomography: A Practical Guide for Radiologists and Clinicians

“…Immunohistochemical studies show that PSMA expression upsurge in hormone-refractory, dedifferentiated, or metastatic PCa and may negatively correlate with survival outcomes. PSMA positron emission tomography (PET)/computed tomography (CT) is used to guide management decisions in clinical practice because of its utility in prognostics [4,5].…”