Trends of upgrading and upstaging of grade group 1 prostate cancer at radical prostatectomy: NCDB and SEER results from 2010 to 2021

Clinical guidelines universally recommend active surveillance—monitoring with curative intent—for indolent-grade group (GG) 1 prostate cancer (PCa). Moreover, a growing body of literature supports reclassifying GG 1 as “non-cancer.” ^[1] However, PCa is often multifocal, and a biopsy may be performed for diagnosis. To assess potential biopsy undersampling, we characterized upgrading and upstaging at radical prostatectomy (RP) among males initially diagnosed with GG1 disease using data from 2 large cohorts: Surveillance, Epidemiology, and End Results (SEER) and the National Cancer Database (NCDB).

We identified patients aged 40 to 75 years with clinically localized (cT1–2) GG 1 PCa diagnosed using biopsy between 2010 and 2021 from the NCDB and SEER who underwent RP as initial treatment. Upgrading was defined as GG 2–5 at RP (clinically significant cancer), and upstaging was defined as pathological stage T3 or 4 (extraprostatic disease). To align with the SEER's limit of ≤24 months from biopsy to RP (first treatment course), we applied the same time restriction in NCDB. A Cochran-Armitage trend analysis was used to assess temporal changes in upgrading and upstaging. All statistical analyses were performed using Stata 17 software (Stata Corporation, College Station, TX). Statistical significance was determined using 2-sided hypotheses with p < 0.05.

In total, 96,929 patients were identified from the NCDB. Among them, 53.5% experienced upgrading at RP, with 7.7% upgrading to GG 3–5. The likelihood of upgrading increased from 43.4% to 68.9% during the 2010–2021 period (p < 0.01). Overall, 13.1% of patients were upstaged to pT3–4, increasing from 9.8% to 21.2% during the study period (p < 0.01). Similar trends were observed in SEER (n = 35,688), with 53.3% upgrading (8.1% upgraded to GG 3–5) and 14% upstaging at the RP. During the study period, upgrading increased from 44.9% to 70.8% (p < 0.01), whereas upstaging increased from 11.1% to 20.0% (p < 0.01; Fig. 1).

Figure 1.

Upgrading and upstaging of GG1 prostate cancer at radical prostatectomy in NCDB (left) and SEER (right). The Cochran-Armitage trend analyses demonstrated significant increases over time (all p < 0.01). GG = grade group; NCDB = National Cancer Database; SEER = Surveillance, Epidemiology, and End Results.

Using contemporary data from 2 nationally representative cohorts, we demonstrate an increase in upgrading and upstaging over the past decade. Recently, Monda et al. ^[2] demonstrated a significant decrease in GG 1 at RP using SEER and Michigan Urological Surgery Improvement Collaborative data, similar to the results from the NCDB ^[3], which reflects a decrease in the surgical overtreatment of PCa, consistent with professional guideline recommendations for active surveillance. This evolution in practice patterns, along with our findings of increased adverse pathology at RP for patients initially diagnosed with GG 1, suggests improved patient selection for surgery. We demonstrated that more than half of the patients with GG 1 on biopsy had a Gleason grade 4–5 component at the RP, which has the potential to metastasize. Up to 14% of patients with GG 1 disease on biopsy have adverse pathological features on RP, that is, upgrading to GG 3 or higher or extraprostatic disease (stage of pT3 or higher). This challenges current efforts to reclassify the GG 1 as noncancerous, which may lead to less rigorous follow-up and vigilance. The limitations of this study include the lack of magnetic resonance imaging and genomic classifier outcomes in the registry data, although only 35% of patients currently undergo prebiopsy magnetic resonance imaging ^[4] and only 11% of patients undergo genomic classifier testing ^[5]. Strengths include large, nationally representative samples encompassing community practices with mirrored results.

In conclusion, our findings demonstrated significant and increased upgrading and upstaging at RP over time, in concert with a decrease in the overtreatment of GG 1 PCa ^[2,3]. However, the significant and increasing numbers of patients with adverse features at RP demonstrate opportunities to improve risk stratification as well as the inaccuracy of designating GG 1 as “non-cancer.”

Acknowledgments

None.

Statement of ethics

Not applicable.

Conflict of interest statement

SW is a member of early career editorial board of Current Urology and confirms no involvement in any stage of this article's review process, ensuring unbiased editorial decision-making. JCH receives research support from Frederick and the Theresa Dow Wallace Fund of the New York Community Trust. JCH receives salary support from NIH R01 CA241758, R01 CA259173, R01 CA273031, PCORI CER-2019C1-15682, and CER-2019C2-17372, and the Prostate Cancer Foundation Challenge Award. No other relationships or activities appear to have influenced the submitted work.

Funding source

None.

Author contributions

ES, SW: Writing – original;

ES, SW, JCH: Data analysis and interpretation, and critical revision of the manuscript;

JCH: Concept, methodology, and supervision.

Data availability

ES and SW had full access to all the data in this study and take responsibility for the integrity of the data and accuracy of the data analysis.

Evan Suzman
Shu Wang
Jim C. Hu
Department of Urology, New York Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA