Evidence map›Paper›PMID 41249719›Full record

SynthesisEuropean journal of nuclear medicine and molecular imaging2026

Therapeutic outcomes of ²²⁵Ac/¹⁷⁷Lu-PSMA combination therapy in advanced metastatic Castration-Resistant prostate cancer: A systematic review and Meta-Analysis.

Zineddine Belabaci, Giulio Brignoli, Thomas Zilli, Miloš Grujić, Issa Mohamad, Akram Al-Ibraheem, Mohamed Shelan, Ali Afshar-Oromieh

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in European journal of nuclear medicine and molecular imaging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Efficacy, safety, and quality of life outcomes of [International urology and nephrology · 2026
    Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Zineddine BelabaciFaculty of Medicine, Djillali Liabes University, Sidi Bel Abbes, Algeria.
Giulio BrignoliDepartment of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Thomas ZilliRadiation Oncology, Oncology Institute of Southern Switzerland (IOSI), EOC, Bellinzona, Switzerland.
Miloš GrujićCenter for Radiation Oncology, University Clinical Centar Kragujevac, Kragujevac, 34000, Serbia.
Issa MohamadDepartment of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan.
Akram Al-IbraheemDepartment of Nuclear Medicine, King Hussein Cancer Center, Amman, Jordan.
Mohamed ShelanDepartment of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. mohamed.shelan@insel.ch.ORCID 0000-0002-6477-6655
Ali Afshar-OromiehDepartment of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTargeted radionuclide therapy (TRT) has become a standard of care for patients with metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177 labeled PSMA radioligand therapy ([¹⁷⁷Lu]Lu-PSMA) is an established and effective treatment option, while [²²⁵Ac]Ac-PSMA shows promise in refractory cases. The tandem use of [225Ac] Ac and [177Lu] Lu-labeled PSMA ligands is currently being explored to harness the complementary advantages of both isotopes. This meta-analysis investigates the efficacy and safety of [²²⁵Ac]Ac -/[¹⁷⁷Lu]Lu-PSMA radioligand therapy (RLT) in patients with mCRPC.

methodsThis systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive literature search was performed in PubMed, EMBASE, Web of Science (WOS), and Scopus databases, covering all records from inception through March 2025. The primary endpoints focused on therapeutic efficacy, assessed through PSA-based biochemical responses. These included any PSA decline, a PSA decline of more than 50% from baseline, stable disease (defined as a PSA increase of < 25% PSA increase or a decrease of < 50%), and progressive disease (defined as an increase of ≥ 25% PSA) following tandem 225Ac-/177Lu-PSMA tandem RLT. Secondary endpoints included overall survival (OS) and treatment-related adverse events. A random-effects model was used to generate pooled proportions through meta-analysis.

resultsEight studies, including a total of 323 patients treated with [²²⁵Ac]-/[¹⁷⁷Lu]-PSMA combination therapy, were analyzed. The pooled response rates showed that 47% (95% CI: 37%-56%) experienced a PSA decline greater than 50%, while 78% (95% CI: 70%-86%) had any measurable PSA decline. The estimated median OS was 11.8 months (95% CI: 9.0-14.6 months). Severe toxicities were infrequent; the most common severe grade ≥ 3 adverse events were anemia (10%) and thrombocytopenia (6%). No cases of grade ≥ 3 xerostomia were reported.

conclusion[²²⁵Ac]Ac-/[¹⁷⁷Lu]Lu-PSMA RLT shows encouraging activity and manageable safety in patients with advanced mCRPC. Given the retrospective nature of the available evidence and limited data, these findings should be further evaluated in prospective trials to determine long-term efficacy and survival outcomes.

Indexed as

ActiniumDipeptidesLutetiumProstatic Neoplasms, Castration-ResistantHumansMaleNeoplasm MetastasisProstate-Specific AntigenRadioisotopesTreatment OutcomeActiniumDipeptidesLutetiumLutetium-177lutetium (177Lu) vipivotide tetraxetanProstate-Specific AntigenRadioisotopes[225Ac] Ac-/[177Lu] Lu-PSMABiochemical responseMetastatic Castration-Resistant prostate cancer (mCRPC)Radionuclide therapy

Identifiers

PMID41249719
PMCPMC13013121

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.