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

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.