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

Vishnu Murthy; Emmanuel Appiah-Kubi; Kathleen Nguyen; Pan Thin; Masatoshi Hotta; John Shen; Alexandra Drakaki; Matthew Rettig; Andrei Gafita; Jeremie Calais; Ida Sonni

doi:10.1186/s41824-023-00178-1

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

Eur J Hybrid Imaging. 2023 Oct 2;7(1):18. doi: 10.1186/s41824-023-00178-1.

Authors

Affiliations

¹ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA.
² Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
³ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA. JCalais@mednet.ucla.edu.
⁴ Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁵ Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.

^# Contributed equally.

Abstract

Purpose: To evaluate whether quantitative whole-body (WB) PSMA-PET metrics under long-term androgen deprivation therapy (ADT) and/or androgen receptor signaling inhibitors (ARSi) are associated with PSA progression.

Methods: Patients who underwent at least 2 ⁶⁸Ga-PSMA-11 PET/CT scans between October 2016 and April 2021 (n = 372) and started a new line of ADT ± ARSi between PET1 and PET2 were retrospectively screened for inclusion. We investigated the association between PCWG3-defined PSA progression status at PET2 and the following PSMA-PET parameters: appearance of new lesions on PET2, ≥ 20% increase in WB-PSMA tumor volume (WB-PSMA-VOL), progression of disease (PD) by RECIP 1.0, and ≥ 30% increase in WB-PSMA-SUV_mean from PET1 to PET2. Spearman's rank correlation coefficients and Fisher's exact test were used to evaluate the associations.

Results: Thirty-five patients were included: 12/35 (34%) were treated with ADT only and 23/35 (66%) with ARSi ± ADT. The median time between PET1 and PET2 was 539 days. Changes (%) in median PSA levels, WB-PSMA-SUV_mean, and WB-PSMA-VOL from PET1 to PET2 were -86%, -23%, and -86%, respectively. WB-PSMA-VOL ≥ 20%, new lesions, RECIP-PD, and WB-PSMA-SUV_mean ≥ 30% were observed in 5/35 (14%), 9/35 (26%), 5/35 (14%), and 4/35 (11%) of the whole cohort, in 3/9 (33%), 7/9 (78%), 3/9 (33%), and 2/9 (22%) of patients with PSA progression at PET2, and in 2/26 (8%), 2/26 (8%), 2/26 (8%), and 2/26 (8%) of patients without PSA progression at PET2 (p = 0.058, p < 0.001, p = 0.058, p = 0.238, respectively). Changes in PSA were correlated to percent changes in WB-PSMA-VOL and WB-PSMA-SUV_mean (Spearman ρ: 0.765 and 0.633, respectively; p < 0.001).

Conclusion: Changes in PSA correlated with changes observed on PSMA-PET, although discordance between PSA and PSMA-PET changes was observed. Further research is necessary to evaluate if PSMA-PET parameters can predict progression-free survival and overall survival and serve as novel endpoints in clinical trials.

Keywords: ADT; ARSi; PSMA-PET; RECIP.