Does total lesion prostate-specific membrane antigen (PSMA) activity on ⁶⁸Ga-PSMA PET/CT correlate with PSA and prostatectomy histopathological/clinical outcomes in patients with localised primary prostate cancer?

Objectives: To evaluate the relationship between total lesion PSMA (PSMA_TL), serum PSA, histopathological findings and biochemical recurrence (BCR) in patients with localised prostate cancer (PCa). Patients and methods: This retrospective study assessed men undergoing ⁶⁸Ga-PSMA-11 PET/CT for newly diagnosed or treatment-naïve PCa localised to the prostate gland. Volumes of interest were manually mapped to derive SUV_max, SUV_mean, PSMA-avid tumour volume and PSMA_TL. PSMA_TL was defined as the product of PSMA-avid primary tumour volume and SUV_mean. Spearman correlation tests evaluated associations between PET parameters and PSA, ISUP GG and radical prostatectomy (RP) histopathological outcomes. Associations between PET parameters and clinical outcomes were determined using Cox proportional hazards regression with results presented as HR and 95% CI. Results: A total of 200 patients were included, with a median age of 68 (IQR 62–73) years, PSA of 9.5 (6.6–13.0) ng/ml and follow-up of 41 (25–60) months. Median PSMA_TL was 29.6 (14.8–54.8) and SUV_max 11.0 (6.8–17.9). PSMA_TL and SUV_max demonstrated a weak correlation with baseline PSA (ρ = 0.334, p < 0.001 and ρ = 0.343, p < 0.001), and PSMA_TL showed a weak correlation with PSA density in the RP subgroup (ρ = 0.242, p = 0.021). Among 109 (54.5%) patients undergoing RP, PSMA_TL and SUV_max showed a weak correlation with ISUP GG (ρ = 0.233, p = 0.015 and ρ = 0.340, p < 0.001). There was a weak correlation between PSMA_TL and primary tumour stage (ρ = 0.244, p = 0.010) and lymph node stage (ρ = 0.259, p = 0.007). PSMA_TL was significantly higher in those with seminal vesicle involvement (p = 0.011), perineural invasion (p = 0.025) and lymphovascular invasion (p = 0.002). BCR occurred in 46 patients (42%), with a 1% increased risk of BCR per unit increase in PSMA_TL (HR 1.01, 95% CI 1.00–1.02, p = 0.011). Conclusions: PSMA_TL correlates with PSA, PSA density, ISUP GG, RP histopathological findings and BCR. As an adjunct to SUV_max, PSMA_TL has the potential to be a useful prognostic tool. Further research is needed to assess its clinical utility.