Pre-therapeutic PSMA PET Imaging Biomarkers Demonstrate Prognostic Value in Patients Undergoing [177Lu]Lu-PSMA Therapy: A Systematic Review and Meta-analysis.

INTRODUCTION

[177Lu]Lu-prostate-specific membrane antigen (PSMA) radioligand therapy can improve outcomes in patients with metastatic castration-resistant prostate cancer, though response is highly variable in clinical practice. We performed a systematic review and meta-analysis to evaluate the prognostic value of pre-therapeutic PSMA PET-derived imaging biomarkers to better inform patient selection for treatment.

METHODS

PubMed, EMBASE, Web of Science, and Scopus were searched from inception to December 2025 in accordance with PRISMA guidelines (PROSPERO CRD420251074879). Pre-therapeutic PSMA PET biomarkers of interest were the mean and maximum standardised uptake value (SUVmean and SUVmax), PSMA tumour volume (PSMA-TV), total lesional uptake (PSMA-TLU), and total lesional quotient (PSMA-TLQ). Outcomes were overall survival (OS), prostate-specific antigen progression-free survival, and 50% reduction in prostate-specific antigen levels (PSA50). Random-effects meta-analyses were performed, prioritising multivariable-adjusted effect estimates. Risk of bias was assessed using the Quality In Prognosis Studies tool.

RESULTS

Thirty-seven studies were included, with 33 contributing to quantitative synthesis (n = 2993). For each unit increase in SUVmean, there was a reduced risk of death (hazard ratio [HR] = 0.88, 95% CI, 0.85-0.92; P < .001) and PSA progression (HR = 0.870, 95% CI, 0.761-0.995; P = .042), along with higher odds of PSA50 response (odds ratio = 2.12, 95% CI: 1.20-3.74; P = .010). Higher PSMA-TV was associated with poorer OS. Composite metrics were prognostic, with PSMA-TLQ demonstrating stronger associations with survival than PSMA-TLU. SUVmax showed limited prognostic value. Most studies were retrospective and were classified as having moderate risk of bias.

CONCLUSION

Baseline PSMA PET-derived biomarkers provide relevant prognostic information and may complement established clinical biomarkers to support risk stratification and patient selection for [177Lu]Lu-PSMA therapy.