Guideline of guidelines: lutetium-177 PSMA radioligand therapy in advanced prostate cancer.
International guidelines largely agree on using 177Lu-PSMA-617 for mCRPC, with a standard regimen of 7.4 GBq every 6 weeks.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This paper synthesizes international guidelines on lutetium-177 PSMA radioligand therapy for prostate cancer, particularly metastatic castration-resistant prostate cancer. It reviews six major society guidelines and highlights consensus on patient selection and dosing. The recommended regimen is 7.4 GBq every 6 weeks for up to six cycles.
Abstract
Objective To synthesise current international guidance on lutetium-177-labelled prostate-specific membrane antigen (177Lu-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 177Lu-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 Documents without therapeutic recommendations or superseded by updated versions were excluded.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 177Lu-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.
Background
The paper addresses the clinical question of how lutetium-177 PSMA radioligand therapy should be implemented in prostate cancer treatment, particularly for metastatic castration-resistant cases. Previous studies like VISION and TheraP have provided evidence for its use, but guidelines vary internationally. This synthesis aims to clarify consensus and highlight emerging indications.
Methods
A structured literature overview was conducted, searching PubMed, EMBASE, and official repositories for guidelines on 177Lu-PSMA-RLT. The study included guidelines from six major societies, focusing on those with explicit recommendations for PSMA-RLT. Documents without therapeutic recommendations or those superseded by newer versions were excluded.
Results
All included societies, except ESMO, endorse 177Lu-PSMA-617 for PSMA-positive mCRPC after ARPI and taxane chemotherapy, based on Level 1 evidence. The recommended regimen is 7.4 GBq every 6 weeks for up to six cycles. NCCN and EAU guidelines also consider taxane-naïve patients progressing after ARPI therapy.
Interpretation
The synthesis shows broad international consensus on the use of 177Lu-PSMA-617, reinforcing its role in mCRPC treatment. However, the lack of updated guidance from ESMO and reliance on existing trials highlight the need for ongoing research. The effect size is clinically meaningful, but further trials are needed to define its role in earlier treatment settings.
Key findings
- 177Lu-PSMA-617 endorsed for PSMA-positive mCRPC post-ARPI and taxane chemotherapy.
- Level 1 evidence from VISION and TheraP trials supports use.
- Regimen: 7.4 GBq every 6 weeks, up to six cycles.
- NCCN and EAU acknowledge expansion into taxane-naïve patients post-ARPI.
- ESMO has not updated guidance on PSMA-RLT.
Limitations
- Guideline synthesis, not original research.
- Relies on existing trials and expert consensus.
- ESMO guidance not updated.
- No new clinical data presented.