BackgroundCurrent studies have shown inconsistent results regarding the impact of baseline alkaline phosphatase (ALP) levels on the prognosis of metastatic castration-resistant prostate cancer (mCRPC) patients who undergo 177Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (PRLT). Therefore, a comprehensive meta-analysis is needed to clarify the implications.MethodsThis study was carried out in full compliance with the PRISMA protocol 2020, and a comprehensive search was conducted through PubMed, Web of Science, and Embase for published literature up to April 1st, 2024. Random-effects models were used to assess the correlation between baseline ALP and overall survival (OS) or progression-free survival (PFS) of mCRPC patients treated with 177Lu-PRLT, with a significance level set at α = 0.05.ResultsA total of 12 articles were included in this study. The pooled effect estimates for baseline ALP and OS were 1.134 (95% CI: 1.035-1.245), I2 = 78.7%, P < 0.05. Regarding baseline ALP and PFS, the pooled effect estimate was found to be 2.14 (95% CI: 1.232-3.718), I2 = 93.3%, P < 0.05. Subgroup analysis revealed minimal heterogeneity among articles using a cut-off value ≥220U/L when examining the association between baseline ALP and OS; whereas for baseline ALP and PFS, there was also minimal heterogeneity observed among articles that adjusted for confounders.ConclusionThis meta-analysis demonstrates a significant association between elevated baseline ALP levels in mCRPC patients prior to 177Lu-PRLT treatment and inferior OS and PFS. Timely monitoring of baseline ALP levels can provide valuable insights for clinical decision-making and patient counseling.