Lutetium-177–PSMA radioligand therapy in metastatic hormone-sensitive prostate cancer: A systematic review of efficacy, safety, and combination strategies
- Study type
- Review article
- Design
- Systematic review following PRISMA guidelines (search of PubMed, Embase, ClinicalTrials.gov and WHO ICTRP; studies from 2010 to 2025)
- Sample size
- 14 studies
- Source
- Urologic Oncology: Seminars and Original Investigations · 2026
In plain words
Lutetium-177-PSMA is a type of targeted radiation treatment that has been used since its approval in 2022 for advanced prostate cancer that no longer responds to castration (hormone) treatment. This review looked at how this treatment works in prostate cancer that has spread but still responds to hormone therapy. Early evidence shows that the treatment is feasible, its serious side effects have been few, and some patients, especially those who had not had any treatment before, showed a promising response. However, the studies are still small and short, so at this stage the treatment should be considered within research or on the advice of the treating doctor.
Key results
Treatment arms and regimens
Lutetium-177-PSMA radioligand therapy (¹⁷⁷Lu-PSMA-RLT) as monotherapy. Dose details in the full text of the paper.
¹⁷⁷Lu-PSMA-RLT combined with androgen deprivation therapy (ADT), chemotherapy, stereotactic body radiotherapy (SBRT) or tandem α-emitters. Dose details in the full text of the paper.
Source of the regimen details: Abstract of the paper; dose details in the full text of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Studies that evaluated ¹⁷⁷Lu-PSMA in patients with metastatic hormone-sensitive prostate cancer (mHSPC) were included. Eligible sources included randomised trials, observational studies and relevant conference abstracts. Further details of patient inclusion criteria are given in the full text of the paper.
Endpoints
Data on study design, population, treatment regimen, PSA response (≥50% decline), progression-free survival (PFS) and toxicity were extracted and synthesised according to PRISMA guidelines.
Safety and side effects
Toxicity was generally low and consisted mainly of dry mouth (xerostomia) and fatigue. Grade ≥3 adverse events were rare. Dosimetry studies confirmed safe kidney and bone marrow exposure.
Clinical significance and place in guidelines
Based on this review, ¹⁷⁷Lu-PSMA-RLT in mHSPC is still investigational and current evidence shows only preliminary signs of efficacy. The FDA approval in 2022 relates to mCRPC. Given the small sample sizes, heterogeneous protocols and short follow-up, these findings are not yet a basis for changing the standard of care. The status of this treatment in clinical guidelines for mHSPC should be checked separately, and its use should preferably be within a clinical trial.
Limitations
Current studies are limited by small sample sizes, heterogeneous protocols and short follow-up. In addition, some of the included sources were conference abstracts and observational studies.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.