Prostate-specific antigen (PSA) screening has helped propel a 50 percent decline in prostate cancer mortality over the past 20 years. However, universal routine PSA testing is no longer recommended because, used in isolation, the test often triggers unnecessary biopsies, over-diagnosis, and potentially unwarranted treatment of low-risk, indolent disease.

As a result, clinicians now employ risk stratification tools such as prostate MRI and novel biomarkers in conjunction with PSA screening to inform decisions about biopsies. In a recent study published in Urology, Department of Urology researchers at NYU Langone’s Perlmutter Cancer Center and NYU Grossman School of Medicine assessed the accuracy of two commonly used tests—4Kscore and SelectMDx—in predicting detection of clinically significant disease in men with elevated PSA levels.

The investigators found that the two tests often yield conflicting guidance on whether to proceed with biopsy. However, the 4Kscore performs significantly better than SelectMDx when combined with MRI. Although further comparative studies are needed, the findings suggest that the 4Kscore may be a better option to guide clinical decision-making.

Biomarkers Aid Tumor Detection

The 4Kscore and SelectMDx tests are validated to predict detection of significant prostate cancer on biopsy (Gleason Grade Group >1). The 4Kscore measures four prostate-specific biomarkers: total PSA, free PSA, intact PSA, and the protein kallikrein 2, which has been shown to be a marker for prostate cancer. SelectMDx is a urine test that measures the expression of two genetic markers for prostate cancer (HOXC6 and DLX1). Both scores also consider other factors, such as the patient’s age, family history, and prior biopsy results.

Several previous studies have looked at the tests individually and reported comparable sensitivity and specificity for detecting clinically meaningful prostate cancer, the NYU Langone investigators note. However, before this study there have been no data directly comparing performance of the two tests.

“Each of these new tests aim to fine-tune the diagnostic decision associated with an elevated PSA, namely whether or not to proceed with prostate biopsy,” says the study’s lead author, James S. Wysock, MD, MS, a urologic oncologist at the Smilow Comprehensive Prostate Cancer Center and assistant professor in the Department of Urology at NYU Langone. “A strength of our study is that all patients underwent both types of tests as well as MRI before biopsy.”

4Kscore Outperforms SelectMDx

For the current study, investigators analyzed results from 114 patients who received 4Kscore and SelectMDx testing. The two tests yielded discordant guidance on whether to perform biopsy in about half the cases. Clinically significant disease was found in 22 (44 percent) of the 50 patients who had biopsy based on the test results.

“Our study illustrates that there is very weak agreement between the two tests on whether to perform biopsy,” says Dr. Wysock. “Based on our results, the two scores would often lead to different biopsy recommendations.”

For example, Dr. Wysock says, if one doctor orders a 4Kscore while a second orders SelectMDx, their decisions on whether to perform a biopsy would be different in about half of all cases.

Researchers also looked at how the two tests performed in men who had elevated PSA and suspicious MRI findings. They found that the specificity of the 4Kscore for detecting cancer was significantly greater in this group of patients compared with SelectMDx, while the 4Kscore still maintained acceptable sensitivity.

“Despite our small sample size, we were able to show significant differences in the performance of the two biomarker scores,” says the study’s senior author, Herbert Lepor, MD, the Martin Spatz Chair and professor in the Department of Urology at NYU Langone. “This is the first study to compare PSA-based (4Kscore) and non–PSA-based (SelectMDx) biomarkers that inform decisions about prostate biopsy.”

While future research is needed to compare these and other commercially available biomarker tests, the current study raises questions about which score should be used to guide decision-making.

“The observed discordance between the two tests is disconcerting,” says Dr. Lepor. “Larger head-to-head studies are needed that capture detection of clinically significant disease in order to optimize use of these biomarkers in practice.”