INTRODUCTION AND AIM: Radioligand therapy (RLT) with Lu-labelled prostate specific membrane antigen ([Lu]Lu-PSMA-X, referring with "PSMA-X" to a generic PSMA chemical compound) inhibitors has emerged as a viable treatment option in metastatic castration resistant prostate cancer patients having previously progressed on taxane and androgen receptor inhibitors. The aim of this study was to perform a systematic review and meta-analysis to assess the therapeutic efficacy of [Lu]Lu-PSMA-X compared to taxane chemotherapy in taxane-chemo-naïve patients with metastatic castration-resistant prostate cancer. MATERIALS AND METHODS: Searches in several bibliographic databases were made using relevant key words, and articles published up to March 2024 were included. The endpoints included prostate specific antigen (PSA) response rate (RR), progression-free survival, and overall survival. Individual patient data were pooled when feasible. PSA50 was defined as the median proportion of patients achieving at least a 50% decline in serum PSA from baseline. A meta-analysis of the PSA50 response rate (proportion meta-analysis) was performed, generating pooled estimates and 95% confidence intervals (95% CI). RESULTS: From the initially selected 8,414 studies published between 2019 and 2023, 24 were included in the [Lu]Lu-PSMA-X treated group and 17 in the taxane treated group. Our findings show that [Lu]Lu-PSMA-X RLT yielded comparable PSA50 responses in taxane-naïve patients versus those receiving taxane chemotherapy, despite considerable study heterogeneity. Notably, the taxane-naïve group had more extensive pretreatment. CONCLUSIONS: This meta-analysis combines the largest cohorts of taxane-naïve mCRPC patients treated with [Lu]Lu-PSMA-X RLT and taxane-treated mCRPC. It underscores similar PSA50 response rates in both groups, suggesting a potential role for [Lu]Lu-PSMA-X RLT in taxane-naïve patients who cannot or choose not to undergo chemotherapy.