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Phys. Eng. Express"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Purpose.<\/jats:italic>\n                    Prostate-specific membrane antigen (PSMA) PET\/CT is routinely used to restage prostate cancer (PCa) in patients with biochemical recurrence (BCR), yet negative scans may still harbor subclinical disease. This study investigated whether radiomics features extracted from recurrence-prone organs on negative [\n                    <jats:sup>18<\/jats:sup>\n                    F]DCFPyL PET\/CT can predict clinical progression (CP) and clinical progression-free survival.\n                    <jats:italic>Materials and Methods.<\/jats:italic>\n                    We performed a post-hoc analysis of 132 patients with BCR (mean age, 74.5 years) who had negative [\n                    <jats:sup>18<\/jats:sup>\n                    F]DCFPyL PET\/CT scans and received no further treatment after imaging recurrence-prone organs, defined as anatomical sites at highest risk for PCa recurrence (prostate bed, lymph nodes, bones, liver, and lungs), were segmented using nnU-Net (TotalSegmentator), and radiomics features were extracted. Machine learning models (XGBoost) and Cox proportional hazards models were evaluated using nested cross-validation (5-fold outer, 3-fold inner). External validation across two independent centers was performed after ComBat harmonization. The effect of reader-assigned diagnostic certainty on predictive performance was also examined. Only recurrence-prone organs were analyzed, as prior studies have shown that more than 80% of PCa recurrences arise in these regions.\n                    <jats:italic>Results.<\/jats:italic>\n                    Median PSA at imaging was 0.74 ng ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    . During a median follow-up of 25.5 months, 42 of 132 patients (31.8%) developed progression. The concordance index improved from 0.65 using clinical variables alone to 0.74 when PET, CT, and clinical features were combined (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05). Predictive performance was strongly influenced by diagnostic certainty, with moderate-certainty negative scans showing higher accuracy than high-certainty negative scans. Radiomics features derived from negative PSMA PET\/CT reflected systemic recurrence risk and were associated with early lung metastases. External validation demonstrated less than 10% reduction in performance despite inter-center differences.\n                    <jats:italic>Conclusion.<\/jats:italic>\n                    Radiomics signatures from recurrence-prone organs on negative PSMA PET\/CT may reveal subclinical disease and provide complementary biomarkers for risk stratification in BCR patients.\n                  <\/jats:p>","DOI":"10.1088\/2057-1976\/ae8450","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:48:07Z","timestamp":1782859687000},"page":"045011","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond the tumor: recurrence-prone radiomics for prognostication in negative PSMA PET\/CT scans of prostate 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