Epidemiologic Trends in Secondary Malignant Neoplasms of the Liver in the United States: A 25-Year Analysis

Sep 23, 2026

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Secondary malignant neoplasms of the liver (SMNL) are more common than primary liver cancers but remain understudied. This study analyzes SMNL-related mortality trends and disparities across the United States using CDC WONDER mortality data (1999–2023) and US Cancer Statistics incidence data for adults aged 45+. Age-adjusted mortality/incidence rates and crude rates are evaluated with Joinpoint regression, revealing rising mortality among older adults and persistent geographic and demographic inequities.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Background and Rationale

Data Sources and Study Design

Mortality Data (1999–2023)

Incidence Data (1999–2021)

Statistical Methods

Age-Adjusted and Crude Rates

Joinpoint Regression

Results Summary

Overall Mortality Trends

Sex, Race, and Geographic Disparities

Shaikh Khalifa Bin Zayed Al Nahyan Medical & Dental College [https://orcid.org/0009-0009-8028-6814](https://orcid.org/0009-0009-8028-6814) Aga Khan University [https://orcid.org/0000-0001-9027-570X](https://orcid.org/0000-0001-9027-570X) Aga Khan University [https://orcid.org/0000-0002-2147-4614](https://orcid.org/0000-0002-2147-4614) Aga Khan University [https://orcid.org/0000-0001-6707-3675](https://orcid.org/0000-0001-6707-3675) Rutgers Health Community Medical Center [https://orcid.org/0009-0009-0547-9296](https://orcid.org/0009-0009-0547-9296) Jefferson Abington Hospital [https://orcid.org/0009-0003-7825-4537](https://orcid.org/0009-0003-7825-4537) Aga Khan University [https://orcid.org/0000-0002-2969-9551](https://orcid.org/0000-0002-2969-9551) Ohio State University Wexner Medical Center Health Inequities, Epidemiology, Mortality, Liver Neoplasms, Neoplasm Metastasis September 16th, 2025 [https://doi.org/10.21203/rs.3.rs-7613109/v1](https://doi.org/10.21203/rs.3.rs-7613109/v1) 􀁱 􀅏 This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License The authors declare no competing interests. Secondary malignant neoplasms of the liver (SMNL) are more common than primary liver cancers but remain understudied. This study provides the «rst nationwide analysis of SMNL mortality trends and disparities in the US. This study analyzed SMNL-related (ICD-10: C78 .7) CDC WONDER mortality data (1999–2023), and US Cancer Statistics incidence data for adults ≥ 45 years, strati«ed by demographics, geography, and primary site. Age-adjusted mortality and incidence rates (AAMRs, AAIRs) and crude mortality rates (CMRs) were reported per 100,000 population. Temporal trends were analyzed using Joinpoint regression. SMNL-related AAMR rose from 23.8 (1999) to 25.1 (2023) . Males accounted for 51.3% of the 597,332 deaths and had higher AAMRs than females throughout. Lung (25 . 6%) and colon (24 . 6%) cancers were the leading primary sites causing SMNL-related deaths. AAIRs and AAMRs (irrespective of metastasis) declined for most primary cancers. CMRs progressively increased across each successive 10-year age group. Non-Hispanic (NH) Blacks had the highest AAMR but with a declining trend, while NH Whites sawa signi«cant increase. West’s AAMRs showed the biggest increase. Rural areas consistently had higher AAMRs. SMNL mortality is rising among older US adults, with disparities. Improved primary cancer survival extends the window for metastatic progression, highlighting the need for better detection and management. Secondary malignant neoplasm of the liver (SMNL) is often more prevalent than primary liver cancer, yet its mortality trends remain underexplored.1 This has been represented in a University of Cologne study where liver metastases (611 cases) outnumbered primary hepatocellular carcinoma (380 cases) among 1,357 tumor samples.2 Liver cancer is the sixth most common cancer worldwide, ranking «fth in men and ninth in women.3 In 2022, the US had the second-highest liver cancer incidence (43,492 cases) and the third-highest mortality (30,931 deaths) .3 The liver is a common site for organ-speci«c metastasis due to its unique microvascular circulation.4, 5 Gastrointestinal, breast, and prostate cancers, along with neuroendocrine tumors and sarcomas, commonly metastasize to the liver.6 While some studies have examined the burden of SMNL in the US using the Surveillance, Epidemiology, and End Results (SEER) database, they provide only limited coverage due to incomplete geographic representation and inconsistent registry inclusion over time.6,7 Although primary liver cancer mortality trends have been previously studied, no large-scale analysis has comprehensively examined SMNL mortality across demographic and geographic factors.8 Liver cancer, often diagnosed at advanced stages, has a poor prognosis due to its rapid progression and the liver’s vulnerability to metastasis,

FAQs

Why study secondary malignant neoplasms of the liver (SMNL)?

SMNL occurs more often than primary liver cancer, but its mortality trends and disparities have been insufficiently studied at a nationwide scale.

What data were used to analyze SMNL mortality trends?

The study used SMNL-related mortality data from CDC WONDER (1999–2023) and incidence data from the US Cancer Statistics database for adults aged 45+ (1999–2021).

Which factors were used to assess disparities in mortality?

Mortality trends were stratified by demographics and geography, including gender, race, region, urbanization status, primary cancer site, and key states defined by the highest and lowest average annual percentage changes.

Sep 23, 2026

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