Prognostic [68Ga]Ga-PSMA-11 PET Biomarkers for [177Lu]Lu-PSMA Radioligand Therapy in Metastatic Castrate-Resistant Prostate Cancer (Asian Population Study).

AIMS: Gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) ([68Ga]Ga-PSMA-11) directed PET/CT reflects PSMA expression at metastatic sites and can hence be a surrogate of lutetium-177 (177Lu) PSMA ([177Lu]Lu-PSMA) radiation delivery. This retrospective analysis aims to explore the association between quantitative baseline [68Ga]Ga-PSMA-11 PET imaging biomarkers and treatment outcomes in our Asian cohort.

METHODS: We included patients with progressive metastatic castrate-resistant prostate cancer (mCRPC) who received [177Lu]Lu-PSMA radioligand therapy at our institution. The association between baseline [68Ga]Ga-PSMA-11 PET parameters (SUVmax, SUVmean, total tumor volume [PSMA-TV], total lesion uptake [PSMA-TLU = PSMA-TV × SUVmean], and total lesion quotient [PSMA-TLQ = PSMA-TV / SUVmean]) and overall survival (OS), prostate specific antigen (PSA) progression free survival (PFS), PSA response, and toxicity were analyzed using univariate analysis. Optimal cut-points were also explored.

RESULTS: Between May 9, 2018 and October 7, 2024, 71 of 84 screened patients were eligible. The median whole-body SUVmean in our cohort was 8.04. Higher PSMA-TLQ and PSMA-TV (per 10-unit increment) were associated with shorter OS (HR 1.005; HR 1.005) and shorter PSA PFS (HR 1.005; HR 1.004). A higher PSMA-TLQ was also associated with poorer odds of PSA response (OR 0.994). Conversely, higher SUVmean was associated with longer PSA PFS (HR 0.911) and improved odds of PSA response (OR 1.34). Higher PSMA-TV (per 10-unit increment) and PSMA-TLU (per 100-unit increment) were associated with increased hematological toxicity (OR 1.008; OR 1.012).

CONCLUSION: PSMA-TLQ and PSMA-TV were negative prognostic markers and SUVmean was a positive prognostic marker among Asian patients with mCRPC who received [177Lu]Lu-PSMA radioligand therapy.