Once upon a time (that is, before the 1990s), prostate cancer was a fearful disease. It was scary because it was silent. Early prostate cancer has virtually no warning signs. By the time there are symptoms like trouble urinating, blood in urine or semen, or lower back pain, chances are high that the tumor has grown large and perhaps begun to spread. If that happens, it is considered incurable.
Back then, detecting prostate cancer when it was still contained was usually the result of a digital rectal exam during a routine physical, or a coincidental finding from another urinary tract operation.
The PSA test
Then, in the mid-1990s, the cancer’s silence was broken. Research revealed a very small voice that says, “I might be here.” That message comes from a telltale biomarker that is measured in a blood sample. It’s called Prostate Specific Antigen, or PSA. It’s a protein found on the surface of all prostate cells, including
cancerous ones. Prostate cells normally “shed” small amounts of PSA into circulation, but when there’s new activity like an infection, having sex, even bike riding or a digital rectal exam, more PSA is released. The amount can be assessed in a lab, and given a numeric score. The higher the number, the more likelihood of abnormal prostate disturbance. In many cases, it’s a cancer tumor—which also emits PSA.
Thus, the PSA test became the standard early warning. It was inexpensive and easy to administer. In addition to doctor visits, screening campaigns were launched. Mobile clinics and men’s health events offered free PSA tests and digital rectal exams. Practically overnight, the blood test started picking up hundreds of thousands of cases that could well have gone unidentified until it was too late. The medical community hopped on the bandwagon. “Screening saves lives” was their slogan. For the next 15 years or so, all men were encouraged to have an annual blood draw, usually starting around age 55, or sooner epending on known risk factors such as family history, race/ethnicity, exposure to toxic substances, etc.
Uh, not so fast…
In 2012, however, the US Protective Services Task Force (USPSTF) put the brakes on broad screening. This panel is not a government agency, but rather a volunteer advisory group. They looked at evidence of unintended harms resulting from the PSA test. By then, a million men annually were having a needle biopsy based on suspicious PSA results. The standard ultrasound-guided biopsy itself had a 30-40% error argin, and it often led to aggressive treatment that left countless men with urinary and sexual side  fects. Keep in mind that science lacked good tools to filter who really needed a biopsy or not. Plus, there were few alternatives to the existing take-no-prisoners approach to treatment—surgery or radiation—that had side effect risks. So, the USPSTF recommended against the test.
Throwing the baby out with the bath
With a dramatic drop in PSA tests, a troubling trend began. As the number of PSA tests decreased, so did the detection of many early-stage prostate cancers. Within 2-3 years, clinical statistics showed that fewer patients were diagnosed with early-stage cancer while more men were being diagnosed with later stage, more aggressive disease which is harder to treat. Experts began connecting the dots. Fewer PSAÂ tests, more potential terminal prostate cancer. Had the task force thrown the baby out with the bath?
To screen or not to screen—that was the question. With the new data, the USPSTF was faced with a dilemma. On the one hand, PSA led to more collateral damage. On the other hand, no PSA led to more possible death sentences. In 2018 they issued this statement: “For men aged 55 to 69 years, the decision to undergo periodic prostate-specific antigen (PSA)-based screening for prostate cancer should be an individual one.” While they qualified this concerning higher-risk groups, and men over 70, their recommendation kicks the dilemma can down the road. Now, it’s up to each man and his doctor.
The case in favor of PSA, or a new middle ground
Many experts are in favor of keeping annual PSA because we now have solutions to its 2 big problems: • It’s not specific just for prostate cancer, so who really needs a biopsy and who doesn’t? • It leads too quickly to a biopsy, and the standard biopsy has a sizable margin of error.
There are two new tools that provide the rationale for keeping the cheap, easy annual PSA test. First, imaging using a special method called multiparametric MRI (mpMRI) reveals any area suspicious for prostate cancer that needs biopsy. Second, sophisticated biomarker tests can tell if prostate cancer is present and how aggressive it is. To illustrate, let’s take a hypothetical patient, Brian.
Brian’s annual PSA was always low, at 2.0, but when he turned 57 it was suddenly up to 4.3. Instead of rushing to biopsy, Brian’s doc ordered a repeat blood test in 2 months to rule out lab error. It comes back at 4.4—no lab error but a slight rise. Brian’s doc prescribes an mpMRI scan. This high resolution, 3- dimensional visual analysis shows nothing alarming, so no biopsy. Brian’s doc says, “See you next year.”
The following year, Brian’s PSA is 4.8. He has another mpMRI. This time it shows a small but suspicious spot on the right side of his prostate. His doctor orders a new urine test called the MPS2 that can tell if Brian has a slow-growing or aggressive prostate cancer. Brian’s result says he has slow-growing cancer. Now, says the doctor, it’s time for a biopsy. With all your test results we can plan a personalized
treatment strategy, but I want you to have the least invasive yet most accurate type of biopsy. Brian returns to the radiology center. While he’s in the mpMRI, the radiologist can see where to place 2 or 3 needles into the precise spot. Brian’s diagnosis of early low-risk cancer is accurate. Since he is still sexually active, he wants a treatment with low side effects. His doctor says he’s a good candidate for Active Surveillance, but Brian doesn’t want to hold off on treatment. His doctor suggests a focal therapy, meaning a targeted treatment to destroy just the tumor while sparing healthy tissue. The cancer is gone with low chance of side effects. Brian opts for a specific method called Focal Laser Ablation. Lucky Brian—the outpatient treatment is successful and he can keep his sex life.
This once-upon-a-time tale has a happy ending for Brian, and thousands of other men who get their PSA checked annually. This new early detection pathway from blood test to imaging/biomarkers identifies who really needs a biopsy. With early diagnosis, there are now alternatives to whole-gland treatments for patients, and this pathway shows they are candidates for them. It’s a new prostate cancer world, all due to a simple starting point: the PSA blood test done every year to listen for that little voice.
