{
  "abstract": "Background: Extrapulmonary poorly differentiated neuroendocrine carcinoma (EP-PD-NEC) is aggressive and heterogeneous. Our primary objective was to assess primary-site differences in bone, brain, liver, and lung metastases recorded at diagnosis. Secondary analyses examined prognostic effect modification and the incremental predictive information in these variables.\n\nMethods: We analyzed Surveillance, Epidemiology, and End Results data from 2010–2023. Strict EP-PD-NEC was defined by ICD-O-3 codes 8013 and 8041–8045. Bone, brain, liver, and lung metastases recorded at diagnosis were evaluated using modified Poisson regression with individual-level heteroscedasticity-consistent standard errors. Overall survival (OS) was analyzed with multivariable Cox models containing primary-site-by-organ interactions. Associations identified in 2010–2017 were reassessed in 2018–2022. Four prespecified ridge-penalized Cox models were developed and temporally evaluated in distant-stage cases with complete four-organ status. Primary prevalence analyses included patients with known status for the organ analyzed; sensitivity analyses recoded unknown status as negative or used multiple imputation.\n\nResults: Among 6,044 eligible patients, 5,820 (96.3%) had complete four-organ information and 2,356 had at least one recorded organ involved. Recorded metastatic prevalence differed across six primary-site groups for every organ (all false-discovery-rate-adjusted P<0.001). Versus genitourinary primaries, pancreatic primaries had higher adjusted prevalence of liver (prevalence ratio [PR] 3.80, 95% confidence interval [CI] 3.39–4.25) and brain metastases (PR 2.86, 95% CI 1.75–4.66). An increasing recorded four-organ count was associated with shorter OS. The global primary-site-by-organ interaction was significant (likelihood-ratio χ²=43.49, 20 df, P = 0.00176), but the full interaction matrix added negligible temporal predictive value (ΔC-index=0.00169). In 1,374 later-period patients, the spectrum model had a C-index of 0.607 (95% CI 0.588–0.624), a 12-month area under the curve of 0.672 (95% CI 0.639–0.706), and a Brier score of 0.196 (95% CI 0.185–0.207). Compared with the four-organ-count model, paired bootstrap differences were 0.0085 (95% CI 0.0035–0.0139) for the C-index, 0.0119 (95% CI 0.0033–0.0231) for 12-month AUC, and −0.0020 (95% CI −0.0038 to −0.0004) for the Brier score. Missing-status analyses produced similar prevalence estimates.\n\nConclusions: Recorded metastatic patterns differed by primary site in EP-PD-NEC. Organ identity added little predictive information beyond the recorded four-organ count, and site-by-organ interactions yielded negligible improvement. Overall discrimination remained modest.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University",
    "Department of Pathology, Longyan First Affiliated Hospital of Fujian Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Huadong Liang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoxin Wu"
    },
    {
      "affs": [
        1
      ],
      "name": "Xinjing Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Qianqian Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Rongjin Qiu"
    },
    {
      "affs": [
        0
      ],
      "name": "Fengxiang Zheng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c4t64f6rasf0z.bib",
  "cited_by": 0,
  "doi": "10.3389/fendo.2026.1975853",
  "fulltext_url": null,
  "id": "c4t64f6rasf0z",
  "issns": [
    "1664-2392"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1975853/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Neuroendocrine Tumor Research Advances"
    ]
  ],
  "openalex": "W7223174014",
  "pdf_url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1975853/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/c4t64f6rasf0z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:20Z",
      "native_id": "10.3389/fendo.2026.1975853",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1975853/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Neuroendocrine Tumor Research Advances",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Primary-site variation in recorded metastatic patterns and survival associations in extrapulmonary poorly differentiated neuroendocrine carcinoma",
  "title_text": "Primary-site variation in recorded metastatic patterns and survival associations in extrapulmonary poorly differentiated neuroendocrine carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:20Z",
  "url": "https://research.draconitic.com/paper/c4t64f6rasf0z",
  "venue": "Frontiers in Endocrinology",
  "versions": []
}