ArticleCancer imaging : the official publication of the International Cancer Imaging Society2026
When PSMA is not enough: the diagnostic blind spots of PSMA PET/CT and the added value of [¹⁸F]FDG in high-risk prostate cancer: dual-tracer cohort study.
Article in Cancer imaging : the official publication of the International Cancer Imaging Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposePSMA PET/CT has transformed prostate cancer management, yet its diagnostic utility is not absolute. It fails to detect PSMA-suppressed disease variants, including treatment-induced neuroendocrine prostate cancer (t-NEPC) and dedifferentiated tumors, and is inherently blind to second primary malignancies (SPMs). This study evaluated the additional diagnostic yield and direct clinical impact of incorporating [¹⁸F]FDG PET/CT into a systematic, indication-driven dual-tracer protocol in high-risk prostate cancer patients.
methodsIn this retrospective, STROBE-compliant, single-center cohort study, 82 patients with histologically confirmed prostate cancer who underwent both [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]FDG PET/CT were analyzed. Clinical indications encompassed suspected SPM, suspected dedifferentiation or t-NEPC, initial staging of very high-risk disease, pre-[¹⁷⁷Lu]Lu-PSMA therapy evaluation, and equivocal PSMA findings. The primary endpoint was the proportion of patients in whom [¹⁸F]FDG PET/CT provided additional diagnostic information. Secondary endpoints included concordance analysis and the rate of management changes.
resultsMedian age was 72 years (IQR 65-75). [⁶⁸Ga]Ga-PSMA-11 demonstrated superior prostate cancer detection compared to [¹⁸F]FDG (70.7% vs. 25.6%; McNemar's p < 0.0001). However, [¹⁸F]FDG PET/CT provided clinically critical additional information and directly altered management in 51.2% of patients (95% CI: 40.6-61.7%). The most impactful contributions were histopathologically confirmed SPM detection (30.5%, predominantly lung and colorectal adenocarcinomas) and identification of PSMA-negative/FDG-positive discordant disease signaling dedifferentiation. No significant correlation was found between PSMA and FDG SUVmax values (Spearman rho = 0.149, p = 0.422), underscoring their biologically distinct and complementary targets.
conclusion[¹⁸F]FDG PET/CT is not a redundant adjunct to PSMA imaging; it fills a critical diagnostic blind spot. When applied through an indication-driven framework, dual-tracer imaging directly reshapes clinical decision-making in more than half of selected high-risk prostate cancer patients, enabling detection of occult malignancies and guiding pivotal treatment decisions that PSMA PET/CT alone cannot support.
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