Genomic risk model validated for prostate cancer risk prediction

The Prostate CAncer integrated Risk Evaluation (P-CARE) model demonstrated the ability to identify patients who are at higher or lower risk of prostate cancer, according to data presented at the 2024 American Society of Human Genetics Annual Meeting in Denver, Colorado.¹

The P-CARE model is now being assessed in the ProGRESS trial.

The P-CARE model—which integrates polygenic score, family history, and continuous genetic ancestry—was developed and validated on data from 646,991 patients enrolled in the Veterans Affairs (VA) Million Veteran Program (MVP). The model was also externally validated on data from 18,457 patients in the PRACTICAL Consortium and 90,069 samples from the NIH's All of Us Research Program.

In the MVP data, findings showed that patients with high P-CARE scores (at or above 80th percentile) had an increased risk of any, metastatic, and fatal prostate cancer compared with patients with median P-CARE scores. Specifically, those with a high P-CARE score had a 2.75 (95% CI, 2.66-2.84) times greater risk of any prostate cancer, a 2.78 (95% CI, 2.54-2.99) times greater risk of metastatic prostate cancer, and a 2.59 (95% CI, 2.22-2.97) times greater risk of fatal prostate cancer compared with patients with median scores.

The investigators then compared outcomes between high-risk (HR>1.5) and low-risk (HR<0.75) P-CARE groups. In total, 271,152 patients (41.9%) had high risk scores and 158,770 patients (24.5%) had low risk scores.

Of these, 45.3% of patients in the high-risk group and 13.7% of patients in the low-risk group experienced any prostate cancer by age 90. The cumulative incidence of metastatic prostate cancer by age 90 was 8.9% vs 1.9% in the high- and low-risk groups, respectively. Similarly, the cumulative incidence of fatal prostate cancer by age 90 was 3.4% in the high-risk group vs 0.8% in the low-risk group.

Based on these data, the authors note that this model “describes a clinically important gradient of prostate cancer risk, identifying individuals at higher and lower risk.”

ProGRESS Trial

The P-CARE model is now being assessed in the ProGRESS trial (NCT05926102), which is assessing the real-world impact of genomic risk information on the screening recommendations provided by physicians.²

The study, conducted in partnership with Broad Clinical Labs and Genomes2Veterans, is now enrolling participants through the VA healthcare system. Patients are eligible for enrollment if they are a Veteran between the ages of 55 to 69, receive regular care at the VA, and do not have a prior history of prostate cancer.

"Biobank-linked health care systems like Veterans Affairs give us a unique opportunity to learn from existing patient data, develop better models, and deliver new paradigms of preventive care to patients," said lead author Jason Vassy, MD, MPH, MS, a clinician-investigator at Veterans Affairs Boston Healthcare System, in a news release on the study.² "Veteran(s) we are now enrolling into the ProGRESS trial will help us understand the potential impact of precision prostate cancer screening on health outcomes."

For the study, participants will be randomly assigned to receive the precision screening intervention or usual care.³ The screening intervention will consist of an interpreted prostate cancer genetic risk assessment report, tailored screening recommendations, and genetic counseling in cases of high genetic risk. Standard care consists of a brochure on shared decision-making in prostate cancer screening.

The primary outcome measures for the study include diagnoses of clinically significant prostate cancer and counts of negative prostate biopsies, as assessed at 7 years. Secondary outcome measures include diagnoses of prostate cancer, counts of prostate biopsies, rates of prostate-specific antigen testing and prostate MRI, self-rated health, and quality of life.

Final completion of the study is anticipated for September 2030.

References

1. Vassy J, Dornisch AM, Karunamuni A, et al. Translating genomic risk models to clinical trials in a learning health system: the Prostate CAncer integrated Risk Evaluation (P-CARE) model. Presented at: 2024 American Society of Human Genetics Annual Meeting. November 5-9, 2024. Denver, Colorado. Board 5171W

2. Broad Clinical Labs and Genomes2Veterans partner on Veterans Affairs' Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS). News release. Broad Clinical Labs. Published online and accessed November 6, 2024. https://www.prnewswire.com/news-releases/broad-clinical-labs-and-genomes2veterans-partner-on-veterans-affairs-prostate-cancer-genetic-risk-and-equitable-screening-study-progress-302296705.html

3. The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS). ClinicalTrials.gov. Last updated February 15, 2024. Accessed November 6, 2024. https://clinicaltrials.gov/study/NCT05926102