What question did this study set out to answer?

The aim was to evaluate whether polygenic risk scores can enhance prostate cancer detection during biopsy.

April 5, 2026

Abstract 3591: Incorporation of polygenic risk scores with PSA testing for prostate cancer risk stratification in men undergoing prostate biopsy.

Key Result

Polygenic risk scores for prostate cancer and benign PSA elevation improved model discrimination for clinically significant prostate cancer from 0.635 to 0.737 when added to clinical features.

Key Points

The aim was to evaluate whether polygenic risk scores can enhance prostate cancer detection during biopsy.
Identified veterans who underwent their first prostate biopsy from October 1999 to September 2021.
Combined genetic data from the Million Veteran Program with traditional risk factors.
Used multivariable logistic regression to compare prediction models with and without genetic scores.
32.9% of 25,222 patients were diagnosed with clinically significant prostate cancer.
Elevated PHS601 score increased risk of significant cancer (OR=1.73).
Higher PSA447 score decreased risk of significant cancer (OR=0.69).
Model discrimination improved significantly when incorporating polygenic scores.

Structured PICO

Does incorporating polygenic risk scores with clinical features improve prediction of clinically significant prostate cancer in men undergoing prostate biopsy?

Population

25,222 veterans who underwent their first prostate biopsy from October 1999 to September 2021, excluding those with prior prostate cancer diagnosis, without pre-biopsy PSA within 90 days, and PSA levels >50 ng/mL. 76.8% White, 19.4% Black or African American.

Intervention

Incorporation of polygenic scores for prostate cancer risk (PHS601) and benign elevated PSA (PRS447) with traditional clinical features

Comparator

Clinical features alone (pre-biopsy PSA, age at first biopsy, race/ethnicity, and smoking status)

Outcome

Clinically significant prostate cancer (Gleason score ≥7)hard clinical

Incorporating polygenic risk scores for prostate cancer and benign PSA elevation significantly improves the prediction of clinically significant prostate cancer on biopsy compared to traditional clinical features alone.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Purpose: While prostate-specific antigen (PSA) screening reduces prostate cancer (PC) mortality, limited discriminatory ability leads to overdiagnosis of indolent disease and missed clinically significant PC. Genetically informed screening strategies utilizing polygenic scores may improve early PC detection. We hypothesized that incorporating polygenic scores for PC risk (PHS601) and benign elevated PSA (PRS447) with traditional risk factors would improve prediction of clinically significant PC on prostate biopsy in a diverse population. Methods: We identified veterans who underwent their first prostate biopsy from October 1999 to September 2021 using the VA Corporate Data Warehouse, with genetic data from the Million Veteran Program. We excluded patients with prior PC diagnosis, those without pre-biopsy PSA within 90 days, and PSA levels 50 ng/mL. The cohort included 25,222 men: 19,376 (76.8%) White, 4,891 (19.4%) Black or African American, and 955 (3.8%) other race/ethnicities. The primary outcome was clinically significant PC (Gleason score ≥7). We evaluated two genetic scores (PHS601 and PSA447, both standardized to z-scores) along with pre-biopsy PSA, age at first biopsy, race/ethnicity, and smoking status. We performed multivariable logistic regression using three progressive models: clinical features alone, clinical features plus PHS601, and clinical features plus both genetic scores. Results: Among 25,222 patients, 8,319 (32.9%) were diagnosed with clinically significant PC. Both genetic scores showed strong independent associations: elevated PHS601 increased risk (OR=1.73, 95% CI: 1.68-1.79, P0.001), while higher PSA447 decreased risk (OR=0.69, 95% CI: 0.67-0.72, P0.001). At PSA of 4 ng/mL, predicted probabilities of clinically significant cancer ranged from 9.1% to 56.9% across PHS601 percentile groups (≤2nd to ≥98th). Model discrimination improved from 0.635 (clinical features alone) to 0.714 (plus PHS601) to 0.737 (both genetic scores, p0.001). Conclusion: Polygenic scores for PC risk and benign PSA elevation significantly improve prediction of clinically significant PC on biopsy compared to traditional risk factors alone. These findings support genetically informed PC screening strategies. Men with low genetic PC risk could defer biopsy until higher PSA values, reducing overdiagnosis, while those with high genetic risk could undergo biopsy at lower PSA thresholds, reducing missed clinically significant PC. Citation Format: Daniel Sabater Minarim, Roshan Karunamuni, Kylie M. Morgan, Tyler Nelson, Craig Teerlink, Julie Lynch, Isla P. Garraway, Anna M. Dornisch, Tyler M. Seibert, Jason L. Vassy, Brent S. Rose. Incorporation of polygenic risk scores with PSA testing for prostate cancer risk stratification in men undergoing prostate biopsy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3591.

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