New Prostate Cancer Screening Tool Offers More Accurate Risk Assessment

A study presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting revealed that a new screening method, P-CARE, which integrates genetics, family history, and ancestry, may offer a more objective risk assessment for metastatic prostate cancer than traditional screening.

Prostate cancer (PCa) screening guidelines often emphasize shared decision-making and individual risk assessment. However, traditional methods of screening based on family history and race are often subjective and inconsistent.

Previous research has demonstrated a strong association between a polygenic hazard score (PHS) derived from 290 genomic variants (PHS290) and the age at which aggressive prostate cancer (PCa) is diagnosed. This association has been consistently observed in large datasets, including the racially and ethnically diverse Million Veteran Program (MVP).

In this study, Dr. Anna Dornisch of the Department of Radiation Medicine and Applied Sciences, UC San Diego, California, and colleagues developed and validated a new screening model called Prostate Cancer Integrated Risk Evaluation (P-CARE) for more precise risk assessment.

The study used genetic and phenotypic data from the diverse MVP (n=648,422) to identify genetic variants associated with Prostate cancer (PCa), aggressive PCa, benign prostatic hyperplasia, or Prostate-specific antigen elevation.

The researchers used a regularized PHS model to fit a PHS with 601 genetic variants (PHS601), using age at diagnosis as the time to event while considering genetic ancestry. They then combined the new PHS with family history and ancestry to create an integrated risk score, P-CARE.

Dr. Dornisch and colleagues found 707 unique candidate variants, with 601 ultimately included in the PHS601 model.

PHS601 was found to improve risk stratification for any prostate cancer, metastatic, and fatal prostate cancer across ancestry groups, including those with African ancestry, who face higher risks of fatal PCa over the older PHS290 model.

Furthermore, the researchers found that patients in the highest 20% of P-CARE had a 6.3 times higher risk of any PCa and a 6.7 times higher risk of metastatic PCa compared to those in the lowest 20%.

The researchers concluded that “P-CARE combines genetic ancestry, family history, and PHS601 to achieve objective risk stratification for metastatic PCa.”

P-CARE is being validated in additional datasets and will be used in a nationwide randomized clinical trial (ProGRESS) to evaluate precision screening in the VA healthcare system.

Reference

Dornisch A, Karunamuni R, Maxwell K, et al. Prostate Cancer Integrated Risk Evaluation (P-CARE): A Model to Stratify Risk of Any, Metastatic, and Fatal Prostate Cancer. Abstract #338. Presented at the 2024 American Society for Radiation Oncology Annual Meeting; September 29-October 2, 2024; Washington DC.