The quantitative impact of prostate-specific membrane antigen (PSMA) PET/CT staging in newly diagnosed metastatic prostate cancer and treatment-decision implications.

Abstract

Objectives: To quantify the stage-shift with prostate-specific membrane antigen (PSMA) PET/CT imaging in metastatic prostate cancer and explore treatment implications.

Methods: Single-centre, retrospective analysis of patients with newly diagnosed [¹⁸F]PSMA-1007 or [⁶⁸Ga]Ga-PSMA-11 PET/CT-detected metastatic prostate cancer who had baseline bone scintigraphy between January 2015 and May 2021. Patients were subclassified into oligometastatic and polymetastatic disease utilizing the STAMPEDE2 trial (ISRCTN66357938/NCT06320067) definition. Patient, tumour, and treatment characteristics were collected. PSMA PET/CT concordance with conventional imaging (bone scintigraphy and low-dose CT of PET) was identified by number and site of metastases, and subgroup assigned. Spearman's rank correlation and linear regression modelling determined the association between the imaging modalities.

Results: We analysed 62 patients with a median age was 72 years (range 48-86). On PSMA PET/CT, 31/62 (50%) patients had oligometastatic disease, and 31/62 (50%) had polymetastatic disease. Prostate radiotherapy was delivered in 20/31 (65%) patients with oligometastatic disease and 17/31 (55%) with polymetastatic disease. 23/62 (37%) patients were reclassified as M0 on conventional imaging. PSMA PET/CT had a 2.9-fold increase in detecting bone metastases. Bone metastases concordance was found in 10/50 (20%) by number and 30/33 (91%) by site. PSMA PET/CT had a 2.2-fold increase in detecting nodal metastases. Nodal metastases concordance was found in 5/46 (11%) by number and 25/26 (96%) by site. There was significant positive correlation between PSMA PET/CT and conventional imaging for detecting bone [R ² = 0.25 (P < 0.001)] and nodal metastases [R ² = 0.19 (P < 0.001)]. 16/31 (52%) had oligometastatic disease concordance.

Conclusion: The magnitude of PSMA PET/CT-driven stage-shift is highly variable and unpredictable with implications on treatment decisions, future trial design, and potentially clinical outcomes.

Advances in knowledge: The magnitude of "frame-shift" with PSMA PET/CT imaging is highly variable and unpredictable which may unreliably change treatment decisions dependent on image-defined disease extent. Prospective randomized trials are required to determine the relationship between PSMA PET/CT-guided treatment choices and outcomes.