Aggressive Prostate Cancer Is Rising in Appalachia, Landmark Study Finds

A sweeping analysis of nearly one million American men has revealed a troubling shift in the geography of aggressive prostate cancer, with incidence climbing steadily in Appalachian communities even as overall diagnosis rates fall across most of the United States. The study, published in Cancer Causes & Control, mined the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database to track how rurality and Appalachian status shaped prostate cancer severity between 2004 and 2022, uncovering patterns that researchers say demand region- and race-specific public health strategies.

The research team, led by investigators at Case Western Reserve University School of Medicine, identified 951,965 men aged 40 and older diagnosed with primary prostate cancer across SEER’s 17 registries, which collectively cover roughly 26.5 percent of the U.S. population. Using county-level Federal Information Processing Standards codes, the scientists sorted every case into four geographic categories: urban Appalachian, rural Appalachian, urban non-Appalachian, and rural non-Appalachian. Rurality was classified with the U.S. Department of Agriculture’s 2013 Rural-Urban Continuum Codes, grouping metropolitan counties (codes 1 through 3) as urban and non-metropolitan counties (codes 4 through 9) as rural.

Aggressiveness was defined with clinical precision. A case was labeled more aggressive if it met at least one of three criteria assessed at diagnosis: a Gleason score of 7 with a 4+3 pattern or scores of 8 through 10, tumor stage T3 or T4, or distant metastasis. Less aggressive disease was confined to Gleason scores of 6 or 7 with a 3+4 pattern, tumor stage T1 or T2, and no distant spread. This composite approach, the authors note, aims to capture clinically meaningful disease severity rather than long-term outcomes, and only 4.1 percent of cases had unknown aggressiveness status, with missingness similar across all geographic groups.

The headline finding concerns time. While overall prostate cancer incidence declined in most regions, the age-adjusted incidence of more aggressive disease rose significantly in both Appalachian categories. Urban Appalachia saw aggressive prostate cancer incidence climb at an annual percent change of 2.73 percent (95 percent confidence interval 1.20 to 4.65), and rural Appalachia rose at 1.91 percent (95 percent CI 0.61 to 3.39). Rural non-Appalachia also increased, though more slowly at 0.97 percent. Meanwhile, rural Appalachia was the only region with a consistent decline in overall incidence, falling at an annual percent change of minus 1.7 percent (95 percent CI minus 2.98 to minus 0.42). After 2016, urban Appalachia showed larger rises than any other region, with notable spikes in 2016, 2017, and 2021.

Metastatic disease told a parallel story. Urban Appalachia recorded the lowest overall metastatic incidence at 11.16 per 100,000 men, while rural non-Appalachia had the highest at 13.86 per 100,000. Rates generally declined through the late 2000s before rebounding, and all four regions increased substantially after 2020, with the overall metastatic rate jumping from 15.30 per 100,000 men in 2020 to 18.32 in 2021 and 19.26 in 2022. The authors attribute this post-pandemic surge to delayed diagnoses stemming from disruptions in PSA screening and routine care during the COVID-19 pandemic, a pattern also documented by the Centers for Disease Control and Prevention.

Multivariable logistic regression exposed how geography and race interact in ways that defy simple assumptions. Among White men, compared with urban non-Appalachia, the odds of more aggressive prostate cancer were higher in rural non-Appalachia (odds ratio 1.077) and rural Appalachia (odds ratio 1.035) but lower in urban Appalachia (odds ratio 0.916). Black men overall faced higher odds of aggressive disease than White men, with the disparity most pronounced in urban areas: odds ratios of 1.085 in urban non-Appalachia and 1.160 in urban Appalachia. Yet in rural Appalachia, the pattern reversed, with Black men showing significantly lower odds of aggressive disease than White men in the same region (odds ratio 0.831), a finding the authors suggest may reflect lower screening uptake and smaller Black populations in those counties.

The paradox of Appalachia, where overall incidence falls while aggressive disease rises, may be rooted in screening behavior. Prior studies cited in the paper found that Appalachian men were 1 to 2 percentage points less likely than age-matched non-Appalachian men to have ever received a serum PSA test or digital rectal examination. Lower screening rates, the researchers propose, could suppress the detection of less aggressive, screen-detected tumors while allowing more dangerous cancers to progress undetected until they present with advanced disease. The authors also point to the evolution of U.S. Preventive Services Task Force guidelines, which recommended against routine PSA screening for men 75 and older in 2008 and against PSA-based screening for all men in 2012, shifts that may have disproportionately affected older and high-risk populations in underserved regions.

Rural areas face compounding structural barriers. The study found that men in rural regions were diagnosed at older ages, more likely to present with aggressive disease, and less likely to receive definitive treatment than their urban counterparts. The authors cite longer travel distances, transportation limitations, fewer healthcare providers and specialists, shortages of urologists, and socioeconomic disadvantages as plausible mechanisms driving more advanced disease at initial diagnosis. Appalachian Regional Commission data indicate substantially lower availability of primary and specialty physicians in rural Appalachian counties than in large metropolitan ones. Notably, the gap between Appalachian and non-Appalachian incidence narrowed between 2011 and 2015, following the Affordable Care Act’s expansion of Medicaid eligibility and increased funding for local health departments in Appalachia, though the authors caution that Medicaid expansion was not uniform across SEER states.

The study carries important caveats. SEER’s coverage of roughly 26.5 percent of the population does not capture the full geographic and demographic diversity of Appalachia, limiting generalizability to the most rural or socioeconomically disadvantaged areas. The researchers used the Appalachian Regional Commission’s 2008 county definition despite later updates, and rurality was based on the USDA’s 2013 codes, which may not reflect temporal shifts in urbanization over the nearly two-decade study window. The authors also note that grouping all non-metropolitan counties into a single rural category may mask important variation in healthcare access, and that relatively small effect sizes, while statistically significant given the enormous sample, should be interpreted with attention to both magnitude and precision.

Still, the implications are clear. Prostate cancer remains the second most commonly diagnosed cancer among American men, with the American Cancer Society estimating approximately 299,010 new cases and 35,250 deaths in 2024. The finding that aggressive disease is climbing in Appalachian communities while overall rates fall suggests that targeted screening outreach, improved access to urological specialists, and race-conscious care strategies are urgently needed in these regions. The authors conclude that prostate cancer burden and severity varied meaningfully by Appalachian status and rurality, and that monitoring these evolving temporal trends will be essential to closing the gap before more dangerous cancers slip through the diagnostic net.

Subject of Research: Geographic disparities and temporal trends in aggressive prostate cancer: a SEER population-based analysis (2004–2022)

Article Title: Geographic disparities and temporal trends in aggressive prostate cancer: a SEER population-based analysis (2004–2022)

Article References: Xu, Y., Singh, A., Li, E., Zaorsky, N. G., Geyer, N., Yang, Y., Yang, Y., McDonald, A. C., Zhang, L., & Wang, M. (2026). Geographic disparities and temporal trends in aggressive prostate cancer: a SEER population-based analysis (2004–2022). Cancer Causes & Control, 37(11), Article 181. https://doi.org/10.1007/s10552-026-02267-5

Image Credits: AI Generated

DOI: 10.1007/s10552-026-02267-5

Keywords: prostate cancer, health disparities, Appalachia, rural health, cancer epidemiology, SEER database, public health, Geographic, disparities, temporal, trends, aggressive