What is the role of PSA and the new 4KScore Test? How does mpMRI fit into this?

PSA in Detection


PSA is a biomarker, that when elevated suggests a patient may have prostate cancer. However, it is not specific for prostate cancer and several other conditions can cause PSA elevation.Men at risk for prostate cancer  were routinely were screened with PSA up until 2012 when the USPSTF task force recommended against screening  because over diagnosis, resulted in overtreatment of nonsignificant cancers, with significant side effects, and escalating costs. USPSTF felt the benefits of screening with PSA did not outweigh the harms. 

USPSTF in April 2017 reversed their decision. Based on data from the ERSPC trial*, that showed PSA screening reduced chances of advanced cancer by 30% and death by 20% they concluded that PSA may be useful and that screening should be a shared decision between patient and physician. *

*www.nejm.org/doi/pdf/10.1056/NEJMoa0810084 ; ERSPC Lancet 2014 ; ERSPC.org

*JAMA USPSTF Revised recommendations April 11 2017; doi:10.1001/jama.2017.4413


Dr. Anthony D'Amico  Head of Radiation Oncology at Brigham and Women's Hospital in Boston states 

"Men at risk for prostate cancer, including black men, should be screened for PSA starting at 40. Men at average risk should be screened starting at 50 with a base screening in their 30s."

The American Cancer Society recommends that men "make an informed decision with their health care provider about whether to be screened for prostate cancer. The decision should be made after getting information about the uncertainties, risks, and potential benefits of prostate cancer screening."

The discussion about screening should take place at:

  • Age 50 for men at average risk of prostate cancer and are expected to live at least 10 more years.

  • Age 45 for men at high risk of developing prostate cancer. This includes African Americans and men who have a first-degree relative (father, brother or son) diagnosed with prostate cancer at an early age (younger than age 65).

  • Age 40 for men at even higher risk (those with more than one first-degree relative who had prostate cancer at an early age).

After these discussions have taken place, men who still want to be screened should get the PSA blood test. The digital rectal exam may also be used as a part of the screening.


There is a new test that overcomes the current disadvantages of standard PSA. This test along with Multiparametric MRI may reduce the incidence of over diagnoses and thereby over treatment. ​


Biomarkers that can differentiate between aggressive cancers and non aggressive cancers are important tools to avoid unnecessary biopsies in patients with elevated PSA. In the first 20 years of PSA development, screening reduced prostate cancer mortality but overdiagnosis and overtreatment has resulted in too many side effects. The 4K test uses 4 different types of PSA proteins along with other clinical information in an algorithm to predict the percent risk for the patient having high grade cancer (gleason 7 or higher) on biopsy. In several peer reviewed publications, the 4K test has shown to improve predictability for aggressive cancer both in biopsy specimens as well as in patients who have had their prostates  surgically removed.

The 4K test may be done in any patient with an abnormal DRE or elevated PSA in whom an initial or repeat biopsy is being considered. The 4K score can be used to select men who are at risk for aggressive cancer  who need treatment. Men with a low 4K score may feel safer to defer biopsy.










The 4K test, is a new blood test that accurately identifies risk of aggressive prostate cancer. It has an important significance in deciding whether to proceed with a biopsy if a patient has an abnormal DRE or elevated PSA. It has accuracy in predicting aggressive cancer and accuracy in predicting metastasis 20 years before it occurs. It also has individual predictive ability so patients can set personal thresholds for themselves along with their care provider based on their age, life expectancy, and health.


The 4K test analyzes 4 different types of PSA-related proteins in blood samples and calculates the likelihood from 1% to 100% that a biopsy would find aggressive cancer. An aggressive cancer is defined as one that has a Gleason score of 7 or above. The 4K test became  FDA approved in 2014 and is paid for by most insurances. The 4k test is better than traditional enhancements of PSA such as PSA density, PSA velocity, and age specific PSA.

A man’s decision to proceed with biopsy  will vary based on many factors including the man’s age, general health status, life expectancy, family history of prostate cancer and ethnicity. Each of these factors will  have a bearing on his risk for cancer. Other factors include his personal preferences, anxiety level and his ability to tolerate uncertainty if he decides to do nothing for a period of time.


For example if the 4K blood test shows he has a 20% risk of  having aggressive cancer if biopsied, a man who is 50 years of age in good health may want to proceed right away to biopsy; whereas a 70 year old who  is of average health may want to do nothing and check his PSA in 6 months.


Men should know that several options are available and there may be more than one right answer provided the man has  had a shared discussion with one or preferably two doctors willing to spend the time and explain the options. 


Role of mpMRI

After the blood test shows a man has a significant risk for having aggressive cancer and he decides to have a biopsy it would be ideal to have an imaging test to see if he has a visible cancer that can be biopsied. Until recently prostate cancer was the only cancer where blind biopsies were being done with an image to guide where to biopsy.With availability of mpMRI, imaging can used as a triage test for men at risk of aggressive prostate cancer  to further confirm the validity of the blood test findings. Patients with a visible lesion  on imaging could have a targeted biopsy. A lesser number of biopsies may be required since there is a target area to biopsy.


As these tests become widely available and standardized several advantages accrue to men who are at risk for prostate cancer. Overdiagnosis may  be reduced because fewer clinically insignificant prostate cancers will be detected by chance as only patients with  a visible suspected area of cancer on imaging  will undergo a biopsy.  Since less men will undergo biopsy there will be less overtreatment. For the same reasons  the  costs and complications of biopsy  will be reduced.   Also risk assignment will improve since men with significant cancers will be biopsied, graded and staged  more accurately.  Biopsy samples will be representative of the whole tumor and less subject to sampling error. This will result in more appropriate treatment choices. Men on active surveillance will have less chances of getting upgraded and upstaged due to initial misclassification. Men with insignificant cancers need not undergo radical therapies due to  fear of  misclassification. Less men will get  radical therapies so costs are contained. Complications of radical treatments  will occur in less number of men since number of radical surgeries and radiation will be reduced.

At HIFU SOLUTION we recommend all men to get a mpMRI prior to biopsy so that targeted biopsies can be done which are more accurate and allow partial treatment of gland with less side effects.