Prognostic role of early prostate specific antigen changes after [¹⁷⁷Lu]Lu-PSMA radioligand therapy of metastasized prostate cancer: A meta-analysis

Background Approximately 10%-20% of prostate cancers progress to metastatic and castration-resistant forms (mCRPC). Radioligand (RLT) therapy with [Lu-177]Lu-prostate-specific membrane antigen (PSMA) is an emerging treatment for metastasized mCRPC and its efficacy is assessed not only but also by prostate specific antigen (PSA) measurement after 12 weeks or more after treatment. Our aim was to evaluate the role of early PSA measurement after RLT in predicting overall survival (OS) of mCRPC patients.Methods A systematic search on PubMed, Web Of Science and Scopus was performed from January to December 2022. PRISMA guidelines for prognostic studies was adopted. Risk of bias was assessed using quality of prognostic studies (QUIPS).Results Twelve studies at low-intermediate risk of bias, were included in the meta-analysis (1646 patients, mean age 70 years). About 50% of patients showed a PSA decline after 1-2 of [Lu-177]Lu-PSMA, and more than 30% reported a PSA decline = 50%. The median OS range for patients with any PSA decline was 13-20 months, while for patients with stable or increased PSA, the median OS fell to 6-12 months. The OS rate for a PSA decline after the one-two [Lu-177]Lu-PSMA cycles was 0.39 (95% CI: 0.31-0.50), while OS for a PSA decline =50% was 0.69 (95% CI: 0.57-0.83).Conclusions A PSA decline is observed in almost 50% of mCRPC patients after 1-2 [Lu-177]Lu-PSMA cycles, with a significantly longer OS compared to stable or increased PSA levels, respectively. Accordingly, any PSA decline after 1-2 cycles of therapy should be regarded as a favourable prognostic factor for OS.