The death rate from prostate cancer in the United States has decreased by more than 40% since the 1990s, largely due to prostate-specific antigen (PSA) screening. The bottom line is that PSA screening has saved the lives of tens of thousands of American men. Therefore, recommendations to abandon PSA screening seem absurd, especially for health care professionals who have watched men die of prostate cancer. Those of us who endorse PSA screening agree that the lack of PSA specificity for significant prostate cancer resulted in hundreds of thousands of men undergoing unnecessary biopsy and tens of thousands undergoing radical prostatectomy or radiation therapy without benefit. Therefore, it is equally absurd to indiscriminately perform biopsies on men with an elevated PSA and offer aggressive treatment for all screen-detected cancers. So what is the solution? We must screen smarter and biopsy smarter, which will allow us to treat smarter! There is emerging evidence that we have the ability to both screen and biopsy smarter.

How can we screen smarter? The following review article provides compelling evidence that the 4Kscore^® Test (OPKO Lab, Nashville, TN) is a useful tool in the identification of those men with an elevated PSA and/or abnormal digital rectal examination results who will be diagnosed with significant prostate cancer following transrectal ultrasound (TRUS) -guided random prostate biopsy. Therefore, one strategy to compensate for the lack of specificity of PSA screening for detecting significant prostate cancer is to perform the 4Kscore Test as a reflex test on those men with an elevated PSA level and perform biopsy only on those men based on a probability that significant disease will be diagnosed. The threshold probability for proceeding with prostate biopsy will vary based on life expectancy.

How can we biopsy smarter? NYU Langone Medical Center (New York, NY) has advocated multiparametric magnetic resonance imaging (MRI) in order to identify the site of significant prostate cancer within the gland. Using MRI/ultrasound fusion biopsy technology, we preferentially biopsy cancer-suspicious regions detected by MRI, which has greatly improved our ability to risk-stratify disease.

For urologists who have yet to embrace MRI imaging and fusion target biopsy, the 4Kscore Test is a reasonable first step to help improve our selection of candidates for TRUS-guided biopsy. Urologists such as I, who routinely obtain an MRI on men with an elevated PSA level, see a substantial percentage of men with a negative MRI result or sites that have a low probability of harboring significant disease. Until now, I have been reluctant to forego prostate biopsy in these cases despite its low diagnostic yield. In these cases, I use the 4Kscore Test to confirm the low risk of significant disease based on MRI results in order to avoid performing a biopsy.

The clinical utility of 4Kscore Test and MRI results is compelling for decreasing unnecessary biopsies and treatment. In men with elevated PSA levels, will the reflex test be the 4Kscore, followed by MRI to guide the biopsy, or MRI followed by the 4Kscore Test? Time will tell. My prediction is that the 4Kscore Test will play a role in selecting appropriate candidates for prostate biopsy. When a biopsy is indicated, it will be guided by findings on MRI.