{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rapizzi E"],"funding":["Associazione Italiana per la Ricerca sul Cancro","Projects of Relevant National Interest (PRIN) 2022","Università degli Studi di Firenze"],"pagination":["33"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12484271"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["36(1)"],"pubmed_abstract":["<h4>Introduction</h4>Paragangliomas (PGLs) are rare malignant non-epithelial neuroendocrine neoplasms characterized by a strong genetic determinism and heterogeneous metastatic potential with no reliable histopathological predictors. In this retrospective study we investigated the role of serum succinate as a biomarker for metastatic risk and developed a novel preoperative scoring tool.<h4>Matherials and methods</h4>Seventy patients with PGLs evaluated between 2006 and 2023 were analysed. Clinical, biochemical, imaging, and genetic data were collected. Germline genetic variants were analysed via Sanger sequencing or NGS through a targeted panel of susceptibility genes. Serum succinate concentrations were quantified by gas chromatography-mass spectrometry.<h4>Results</h4>Succinate levels were significantly higher in patients with Cluster 1 genetic variants (p < 0.001), extra-adrenal PGLs (p = 0.006), and metastatic disease (p = 0.024). We developed a novel preoperative risk assessment tool, the P-SMART (Preoperative Succinate MetAstatic Risk Tool), combining serum succinate levels, tumour size, and location. P-SMART assigns: 3 points for extra-adrenal localization, 3.5 points for serum succinate ≥ 8.95 µM, and 3 points for tumour size ≥ 7.0 cm. In our cohort a P-SMART score > 4.75 predicted metastatic disease with 72.7% sensitivity and 83% specificity, outperforming the ASES score (Age, Size, Extra-adrenal, Secretory type; AUC 0.891 vs 0.752, p = 0.005).<h4>Conclusions</h4>Though limited by sample size and retrospective design, our findings suggest that succinate is a minimally invasive biomarker that could enhance preoperative metastatic risk stratification, especially when integrated into a multiparametric score such as P-SMART. Larger prospective studies are needed to validate its role, but P-SMART could optimize clinical decision-making, refine patient selection for whole-body imaging, reduce unnecessary radiation exposure, and inform surveillance strategies."],"journal":["Endocrine pathology"],"pubmed_title":["Presurgical Succinate MetAstatic Risk Tool (P-SMART) in Paragangliomas."],"pmcid":["PMC12484271"],"funding_grant_id":["CUP B53D23021440001","CUP B53D23021320001","IG 2020-ID 24820"],"pubmed_authors":["Staderini F","Rapizzi E","Maggi M","Sparano C","Galeotti N","Ercolino T","Santi A","Amore F","Zanatta L","Canu L"],"additional_accession":[]},"is_claimable":false,"name":"Presurgical Succinate MetAstatic Risk Tool (P-SMART) in Paragangliomas.","description":"<h4>Introduction</h4>Paragangliomas (PGLs) are rare malignant non-epithelial neuroendocrine neoplasms characterized by a strong genetic determinism and heterogeneous metastatic potential with no reliable histopathological predictors. In this retrospective study we investigated the role of serum succinate as a biomarker for metastatic risk and developed a novel preoperative scoring tool.<h4>Matherials and methods</h4>Seventy patients with PGLs evaluated between 2006 and 2023 were analysed. Clinical, biochemical, imaging, and genetic data were collected. Germline genetic variants were analysed via Sanger sequencing or NGS through a targeted panel of susceptibility genes. Serum succinate concentrations were quantified by gas chromatography-mass spectrometry.<h4>Results</h4>Succinate levels were significantly higher in patients with Cluster 1 genetic variants (p < 0.001), extra-adrenal PGLs (p = 0.006), and metastatic disease (p = 0.024). We developed a novel preoperative risk assessment tool, the P-SMART (Preoperative Succinate MetAstatic Risk Tool), combining serum succinate levels, tumour size, and location. P-SMART assigns: 3 points for extra-adrenal localization, 3.5 points for serum succinate ≥ 8.95 µM, and 3 points for tumour size ≥ 7.0 cm. In our cohort a P-SMART score > 4.75 predicted metastatic disease with 72.7% sensitivity and 83% specificity, outperforming the ASES score (Age, Size, Extra-adrenal, Secretory type; AUC 0.891 vs 0.752, p = 0.005).<h4>Conclusions</h4>Though limited by sample size and retrospective design, our findings suggest that succinate is a minimally invasive biomarker that could enhance preoperative metastatic risk stratification, especially when integrated into a multiparametric score such as P-SMART. Larger prospective studies are needed to validate its role, but P-SMART could optimize clinical decision-making, refine patient selection for whole-body imaging, reduce unnecessary radiation exposure, and inform surveillance strategies.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-04T16:49:24.317Z","creation":"2026-05-13T14:24:30.962Z"},"accession":"S-EPMC12484271","cross_references":{"pubmed":["41026309"],"doi":["10.1007/s12022-025-09878-9"]}}