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Prostate-specific membrane antigen (PSMA) PET-CT complements mpMRI, with prospective studies showing high sensitivity and negative predictive value and detection of cancers missed by mpMRI. Structured reporting systems, including the PRIMARY score, support standardisation. 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European Radiology (2026) 36:7063–7072  \n[https://doi.org/10.1007/s00330-026-12596-3](https://doi.org/10.1007/s00330-026-12596-3)  \nSPECIAL REPORT Open Access  \nPSMA PET: the answer to MRI-occult prostate cancer… or another mirage?  \nThomas Wagner 1,2* , Mark Emberton3, Iztok Caglic2,4, Dimitris Priftakis5, Francesco Giganti3,4  \n,  \nVeeru Kasivisvanathan6,7 and Shonit Punwani2  \nAbstract  \nMultiparametric MRI (mpMRI) has transformed the diagnostic pathway for suspected prostate cancer by improving the detection of clinically significant prostate cancer (csPCa) and reducing unnecessary biopsies. However, its negative predictive value declines in higher-risk populations, and up to 30% of men with negative or indeterminate mpMRI (PIRADS 1–3) may still harbour csPCa, particularly those with adverse clinical features. Variability in MRI quality, reader expertise, and reference standards further limits reproducibility outside expert centres. Prostate-specific membrane antigen (PSMA) PET-CT has emerged as a promising complementary modality. Beyond its role in staging and recurrence, prospective studies support its value in the pre-biopsy setting. Trials such as PRIMARY, PEDAL, and others demonstrate that PSMA PET/CT can detect a substantial proportion of csPCa missed by mpMRI, with high sensitivity and negative predictive value. The development of structured reporting systems, notably the PRIMARY score, represents an important step towards standardisation and improved comparability across studies. Despite encouraging diagnostic performance, critical uncertainties remain. The biological significance of PSMA-positive, MRInegative lesions is unclear, and higher detection rates may partly reflect intensified sampling rather than clinically meaningful disease. Cost-effectiveness, optimal patient selection, and the positive predictive value of PSMA-avid lesions in MRI-negative prostates require further prospective validation. This opinion piece reviews high-quality prospective evidence and argues that PSMA PET/CT has the potential to refine risk stratification and reduce unnecessary biopsies in selected men with persistent suspicion of prostate cancer. Integration into diagnostic pathways should be guided by imaging performance and biological relevance, ensuring that the detected disease is clinically meaningful.  \nKey Points  \nQuestion Can PSMA PET/CT improve risk stratification and reduce missed clinically significant prostate cancer in men with negative or indeterminate mpMRI?  \nFindings Prospective studies show PSMA PET/CT complements mpMRI, achieving high sensitivity and negative predictive value while detecting a substantial proportion of significant cancers missed by MRI.  \nClinical relevance PSMA PET/CT may help safely avoid unnecessary biopsies and identify clinically significant disease in selected men after negative or equivocal MRI, but adoption requires standardised reporting, biological validation of PSMApositive/MRI-negative lesions, and careful evaluation of cost-effectiveness within routine clinical pathways.  \nKeywords Prostate cancer, MRI, PSMA PET/CT  \n*Correspondence: Thomas Wagner  \n[thomas.wagner@nhs.net](thomas.wagner@nhs.net)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2026 . Open Access This article is licensed under a Creative Commons Attribution 4 . 0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you","cbCaij5kPh8Dysga","https://ap.wps.com/l/cbCaij5kPh8Dysga","pdf",903052,"English","# Abstract\n# Key Points\n# Graphical Abstract\n# Background\n## Limitations of mpMRI","[{\"question\":\"Why can mpMRI miss clinically significant prostate cancer in higher-risk patients?\",\"answer\":\"Its negative predictive value declines as disease prevalence and risk increase. Variability in MRI quality, reader expertise, and reference standards can also limit reproducibility outside expert centres.\"},{\"question\":\"How does PSMA PET/CT complement mpMRI?\",\"answer\":\"Prospective studies show PSMA PET/CT achieves high sensitivity and negative predictive value while detecting a substantial proportion of significant cancers missed by mpMRI, including in the pre-biopsy setting.\"},{\"question\":\"What are the main uncertainties about PSMA PET/CT findings in MRI-negative cases?\",\"answer\":\"The biological significance of PSMA-positive, MRI-negative lesions is unclear, and higher detection rates may reflect intensified sampling rather than clinically meaningful disease. Cost-effectiveness, patient selection, and positive predictive value also require further prospective validation.\"}]","PSMA PET: the answer to MRI-occult prostate cancer - Open Access Special Report | PDF",1790111976,25]