Guideline of guidelines: lutetium-177 PSMA radioligand therapy in advanced prostate cancer.

[OBJECTIVE] To synthesise current international guidance on lutetium-177-labelled prostate-specific membrane antigen (Lu-PSMA) radioligand therapy (RLT) across the prostate cancer disease spectrum, with emphasis on metastatic castration-resistant prostate cancer (mCRPC) and emerging earlier-line indications.

[METHODS] A structured literature overview was conducted. PubMed, EMBASE, and official repositories of major urological, oncological, and nuclear medicine societies were searched from inception to 31 October 2025 for prostate cancer guidelines. National and international guidelines or consensus statements published in English were eligible if they provided explicit recommendations regarding Lu-PSMA-RLT in their most recent version. Documents without therapeutic recommendations or superseded by updated versions were excluded. Six major society guidelines were included: European Association of Urology (EAU 2025), American Urological Association/Society of Urologic Oncology (AUA/SUO 2023), National Comprehensive Cancer Network (NCCN 2025), Canadian Urological Association (CUA 2024), American Society of Clinical Oncology (ASCO 2025), and European Society for Medical Oncology (ESMO 2020). The joint European Association of Nuclear Medicine/Society of Nuclear Medicine and Molecular Imaging (EANM/SNMMI 2023) procedural guideline and expert consensus from the Advanced Prostate Cancer Consensus Conference (APCCC 2024) were also reviewed.

[RESULTS] All societies except ESMO, which has not yet updated its guidance on PSMA-RLT, endorse Lu-PSMA-617 for PSMA-positive mCRPC following prior androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy, supported by Level 1 evidence from the VISION and TheraP trials. Following PSMAfore, NCCN version1.2025, and more cautiously the EAU 2025 guideline, acknowledge expansion into taxane-naïve patients progressing after ARPI therapy. The recommended regimen remains 7.4 GBq every 6 weeks for up to six cycles with concurrent androgen deprivation therapy and multidisciplinary oversight.

[CONCLUSIONS] International guidelines largely converge on patient selection, dosing, and multidisciplinary implementation of PSMA-RLT. Ongoing trials including PSMAfore, PSMAddition, UpFrontPSMA, ENZA-p, and LuTectomy are expected to further define its role in earlier and combination treatment settings.