341 Background: Prostate cancer represents a heterogeneous disease with varying clinical significance, from indolent cases requiring minimal intervention to aggressive malignancies with high mortality. High-grade prostate cancer, defined as Gleason score ≥8 (Grade Group ≥4), is associated with increased metastatic potential and reduced cancer-specific survival. This study evaluated changes in prostate cancer grade over time in the USA. Methods: Using the most recent National Cancer Data Base from 2025, we identified all men diagnosed with prostate cancer from 2004 to 2022. High grade disease was defined as biopsy Gleason Score ≥ 8 (Grade Group ≥4). Results: A total of 2,259,526 men diagnosed with prostate cancer were identified, of whom 423,953 (18.8%) had high-grade disease. The proportion of newly diagnosed high-grade cases rose from 12,297 (11.9%) in 2004 to 35,193 (24.9%) in 2022. Univariate logistic regression showed increasing age, Black identifying (vs. White), and diagnosis at non-academic centers (vs. academic) as associated with higher odds of high-grade disease. In multivariate analysis, increasing age (OR 1.058 per year 95% CI 1.058–1.059, p<0.001), academic center (vs. non-academic) (OR 1.038 95% CI 1.03–1.05, p<0.001), and racial identity (Black vs. White OR 1.25 95% CI 1.24–1.27, p<0.001; American Indian/Alaskan Native vs. White OR 1.27 95% CI 1.19–1.36, p<0.001) were associated with higher likelihood of high-grade disease. Conclusions: We observed a continuous rise in high-grade prostate cancer incidence suggesting an identified cause. While the unadjusted proportion of high-grade diagnoses was lower at academic centers, after adjusting for age, the odds were actually higher at academic centers compared to non-academic. The increasing incidence of high-grade disease may reflect improved diagnostics (e.g., MRI-targeted biopsy), but the steady rise—alongside more metastatic disease—may signal a concerning shift in the underlying biology of prostate cancer that warrants further study. Acknowledgements: The National Cancer Database (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC’s NCDB and participating hospitals are the source of the de-identified data used herein; they have not verified and are not responsible for the statistical validity or the conclusions drawn by the authors. Proportion of high-grade disease by era and treatment center. Era Percent of men with high grade disease at diagnosis overall Percent of men with high grade disease, diagnosed at academic center (Unadjusted)* Percent of men with high grade disease, NOT diagnosed at academic center (Unadjusted) 2004-2007 12.2% 11.76% 12.42% 2008-2011 13.4% 12.59% 13.87% 2012-2017 21.0% 20.27% 21.53% 2018-2022 24.7% 24.18% 25.02% *After adjusting for age, the odds of high-grade diagnosis were higher at academic centers than non-academic.
Krishnan et al. (Sun,) studied this question.