The PRISMA-2020-checklist.

<div><p>Background</p><p>Current 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.</p><p>Methods</p><p>This 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 <i>α</i> = 0.05.</p><p>Results</p><p>A total of 12 articles were included in this study. The pooled effect estimates for baseline ALP and OS were 1.134 (95% <i>CI</i>: 1.035–1.245), <i>I</i><sup><i>2</i></sup> = 78.7%, <i>P</i> < 0.05. Regarding baseline ALP and PFS, the pooled effect estimate was found to be 2.14 (95% <i>CI</i>: 1.232–3.718), <i>I</i><sup><i>2</i></sup> = 93.3%, <i>P</i> < 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.</p><p>Conclusion</p><p>This 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.</p></div>