Journal of the National Cancer Institute · 2026
Polygenic risk scores for premagnetic resonance imaging risk stratification in men with clinically suspected prostate cancer.
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Fischer Max P, Mayer Alena, Braun Alice, Kraft Julia, Hansen Carla M, Baumgärtner Georg Lukas, Asbach Patrick, Padhani Anwar R, Penzkofer Tobias, König Frank, Awasthi Swapnil, Makowski Marcus R, Ripke Stephan, Hamm Charlie Alexander
Аннотация
BACKGROUND: Men with suspected prostate cancer undergo magnetic resonance imaging (MRI) before biopsy. However, approximately 30%-50% of MRIs are negative (Prostate Imaging-Reporting and Data System [PI-RADS] score 1-2), representing a challenge for MRI resource utilization. This study evaluates prostate cancer polygenic risk scores and clinical markers to optimize MRI utilization.
METHODS: In this prospective study, 500 cancer-suspected men of Western European descent scheduled for MRI (September 2017-December 2022) were enrolled. Exclusions included prior prostate cancer diagnosis, missing serum prostate-specific antigen (PSA), or PSA levels of at least 25 ng/mL. Patient-specific prostate cancer polygenic risk scores were calculated using genotype data obtained from saliva-derived DNA samples. Participants were grouped as MRI negative and positive (PI-RADS score 3-5). Logistic regression was used to calculate odds ratios (ORs) and to build multivariable risk models, including age, PSA, and polygenic risk scores for MRI positivity. Clinical utility was tested in a holdout test set using decision curve analysis.
RESULTS: A total of 386 men (median age = 65 years, interquartile range [IQR] = 53-77 years) were eligible for analysis, which showed statistically significant associations between prostate cancer polygenic risk scores (OR = 1.56, 95% confidence interval [CI] = 1.23 to 1.98; P < .001) with MRI positivity, while PSA alone did not (OR = 1.17, 95% CI = 0.93 to 1.46; P = .18). The highest net benefit was shown using a multivariable age and prostate cancer polygenic risk score model, increasing the proportion of MRI-positive men by 14% compared with PSA alone (60% and 46%, respectively; P = .011).
CONCLUSIONS: Genotype-informed risk stratification using prostate cancer polygenic risk scores could increase the proportion of cancer-suspicious findings at MRI, while identifying those who could safely avoid unnecessary MRI.
METHODS: In this prospective study, 500 cancer-suspected men of Western European descent scheduled for MRI (September 2017-December 2022) were enrolled. Exclusions included prior prostate cancer diagnosis, missing serum prostate-specific antigen (PSA), or PSA levels of at least 25 ng/mL. Patient-specific prostate cancer polygenic risk scores were calculated using genotype data obtained from saliva-derived DNA samples. Participants were grouped as MRI negative and positive (PI-RADS score 3-5). Logistic regression was used to calculate odds ratios (ORs) and to build multivariable risk models, including age, PSA, and polygenic risk scores for MRI positivity. Clinical utility was tested in a holdout test set using decision curve analysis.
RESULTS: A total of 386 men (median age = 65 years, interquartile range [IQR] = 53-77 years) were eligible for analysis, which showed statistically significant associations between prostate cancer polygenic risk scores (OR = 1.56, 95% confidence interval [CI] = 1.23 to 1.98; P < .001) with MRI positivity, while PSA alone did not (OR = 1.17, 95% CI = 0.93 to 1.46; P = .18). The highest net benefit was shown using a multivariable age and prostate cancer polygenic risk score model, increasing the proportion of MRI-positive men by 14% compared with PSA alone (60% and 46%, respectively; P = .011).
CONCLUSIONS: Genotype-informed risk stratification using prostate cancer polygenic risk scores could increase the proportion of cancer-suspicious findings at MRI, while identifying those who could safely avoid unnecessary MRI.