We demonstrated here that the PCPT risk calculator effectively stratified the risk of being diagnosed with prostate cancer diagnosis in a high-risk screening population, including a large number of young, primarily AA men with a low baseline PSA. Specifically, men with a 20% increased PCPT risk score had a nearly three-fold increased risk of being diagnosed with prostate cancer. Furthermore, men who had a significantly higher baseline PCPT risk score had a significantly increased risk of being diagnosed with Gleason ≥ 7 cancers as well.
In the initial description of the PCPT calculator by Thompson et al.4
, PSA, family history, and abnormal DRE were significant predictors of prostate cancer on biopsy, while patients with a history of prior negative prostate biopsy were found to be at a reduced risk of diagnosis of prostate cancer.4
Significant predictors for Gleason ≥7 cancers in this study included PSA, abnormal DRE, age, and AA race. However, the cohort originally used to generate the PCPT risk calculator was composed primarily of older (mean age 62 at enrollment, 70 at biopsy) men, the majority of whom were educated and were white (95.6%).4
In addition, patients with a baseline PSA>3.0ng/ml were excluded from the study.4
This study supports further evaluation of the PCPT risk calculator in an ethnically-diverse group of patients at high-risk for prostate cancer.
Although a previous validation of the PCPT risk calculator has been performed, 6
the population from that follow-up study was composed of 13% African American, 37% Hispanic, and 49% non-Hispanic white patients. The present evaluation of the Fox Chase Cancer Center PRAP population therefore represents an evaluation of the PCPT risk calculator in a unique group of patients. In PRAP, the majority (61.2%) of men are African American, while Caucasians have either a family history of prostate cancer or BRCA 1/2 mutation. Therefore, the present study demonstrates the ability of the PCPT calculator to stratify prostate cancer risk in this cohort, further expanding the applicability of this predictive model.
The interpretation of serum PSA for prostate cancer risk has continued to evolve. While a threshold PSA of 4.0ng/ml was initially used to determine which patients should undergo prostate biopsy, additional studies have recommended biopsy at PSA levels of 2.5 or even 1.5 ng/ml.11,14,15
Prostate cancer risk has been found to exist as a continuum with increasing PSA.4
As such, PSA has been increasingly viewed as a variable which should be interpreted in the context of a patient's other risk factors for prostate cancer. Variables such as advancing age, family history, DRE, previous prostate biopsy, and race can individually provide information to predict the likelihood of developing prostate cancer. The use of predictive tools such as the PCPT risk calculator, which incorporate the impact of these various factors together to determine a patient's risk for prostate cancer diagnosis, can therefore provide valuable information for patient counseling and risk-stratification. After further characterization, such a risk stratification tool may be used to target those high-risk patients who may benefit most from preventative measures or clinical trials. As additional means for predicting prostate cancer such as genetic markers, biomarkers, and imaging studies are developed and refined, they can be incorporated into such existing predictive tools as well.11-13
There are some limitations to this study. The average follow-up in PRAP is approximately 60%, which may hinder the interpretation of our findings since not all prostate cancers may have been detected. In addition, not all participants underwent prostate biopsy, which may have underestimated the true incidence of prostate cancer. Although our sample size was relatively small, we still found that the PCPT risk calculator was able to stratify high-risk men who developed any prostate cancer as well as high-grade disease. Further study in high-risk men is needed in order to improve the accuracy of risk prediction and assessment of prostate cancer.