Beyond prostate-specific antigen: alternatives for prostate neoplasm screening

Abstract

Prostate adenocarcinoma (PCa) is one of the most prevalent cancers in the world. Second only to lung cancer, the key to its successful treatment is in its early detection. With the introduction of prostate-specific antigen in the early 1990s, a screening test involving measuring levels of this protein was developed to detect PCa in asymptomatic individuals. This test is also known as the PSA test. PCa-specific mortalities have been in decline since the test's introduction.

Despite this decline, recent studies have called the efficacy of the PSA test into question. Two large randomized controlled trials conducted in the US and Europe reveal contradicting results as to PSA's accuracy and usefulness. Concerns of overdiagnosis and overtreatment as the result of using PSA screening has led to many national organizations recommending caution or even recommending against its use. Through a thorough review of a large collection of current PCa literature, this study reviews the flaws of using PSA to screen for PCa and investigates alternative approaches currently being pursued through active research to make PCa early detection more accurate. These approaches include improving the accuracy of the PSA screen using PSA-derived testing methods, using PCa-induced epigenetic modifications as a new target for PCa screening, and using urine biomarkers. All of these methods were compared using area under the curve (AUC) values obtained via receiver operating characteristic analysis.

Each method has its own flaws but by comparing each of the different approaches, I was able to conclude that out of the currently available screening methods, screening for Engrailed-2 protein in urine is the most promising screening method with the highest AUC values compared to the other methods. Although this method has been introduced in the UK, it has not been introduced in the US yet. Epigenetic screening methods hold the most promise for accurate PCa screening in the future as it confers the highest accuracy in detecting PCa. However, as it hasn't been shown that epigenetic modifications can be easily obtained in the urine or blood serum for easy and accurate screening, I believe more work has to be done in order for it to be successful in being applied as a screening test. By determining the most promising screening type, we can focus resources and efforts towards finding a way to detect PCa early, allowing for successful treatment.