The Role of Dominant Lesion Site and SUVmax in the Depth of PSA Response in Metastatic Hormone-Sensitive Prostate Cancer

Background/Objectives: Depth of prostate-specific antigen (PSA) response is prognostic in metastatic hormone-sensitive prostate cancer (mHSPC), and the SUVmax of the most avid lesion is a readily available parameter on staging PSMA PET/CT. Uptake intensity and the anatomical site of that lesion are, however, distinct features. This study evaluated their associations with the depth of PSA response. Methods: In this retrospective single-centre study of men receiving androgen deprivation therapy plus an androgen receptor pathway inhibitor (ARPI), the SUVmax and anatomical site of the dominant lesion were derived from baseline 68Ga-PSMA-11 PET/CT. The primary outcome was a PSA nadir < 0.2 ng/mL, analysed using logistic regression with sequential adjustment and within strata defined by disease burden. Progression-free survival (PFS) was a secondary outcome. Results: Among 100 men with evaluable baseline PET/CT, SUVmax was associated with neither PSA response depth nor PFS in any parameterisation examined. A deep PSA response was achieved by 72%, 52% and 29% of patients with prostate-, node- and bone-dominant disease (trend p < 0.001), with median nadirs of 0.08, 0.19 and 0.50 ng/mL. Among patients with bone metastases, a deep response occurred in 29% with bone-dominant disease and 57% with a dominant lesion elsewhere (p = 0.016). The association persisted across sequentially adjusted models (OR range 0.22–0.33) and within high-volume disease (p = 0.008). Under a six-month landmark, deep PSA response was associated with longer PFS (HR 0.10, 95% CI 0.01–0.42), whereas bone dominance was not. Conclusions: The site of the dominant PSMA PET/CT lesion, but not its SUVmax, was associated with the depth of PSA response in ARPI-treated mHSPC. These findings require prospective validation.