Treating prostate cancer is filled with guesswork and uncertainty. Most prostate cancers are tiny and will never leave the prostate or cause any harm. But a few of these small cancers will ultimately be fatal.
One of the reasons why the data on prostate screening have been confusing has to do with the fact that there has been no good way to determine which cancers will become deadly.
Now researchers at Columbia University Medical Center may have found a way. The presence or absence of three genes appears to determine these small tumors' fate. If the genes are present, the tumors will cause little if any trouble.
If the genes are absent, the tumors are aggressive and likely to spread beyond the prostate, leading to advanced prostate cancer.
The three-gene biomarker could take much of the guesswork out of the diagnostic process and ensure that patients are neither overtreated nor undertreated.
In a blind test of 43 biopsy specimens from patients with prostate cancer who had been monitored for at least ten years, the genetic test correctly identified all 14 men whose prostate cancer eventually became dangerous and spread.
“The bottom line is that, at least in our preliminary trial, we were able to accurately predict which patients with low-risk prostate cancer would develop advanced prostate cancer and which ones would not,” said researcher Cory Abate-Shen, a professor of urology and Associate Director of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center in a statement.
Doctors currently use several tests to diagnose prostate cancer and determine its severity. The first suggestion of prostate cancer comes either from a PSA test or a digital rectal exam. If these tests raise concern, a man is often advised to undergo a biopsy, in which a sample of prostate tissue is taken and examined microscopically.
Under the microscope, prostate cancer shows up as aberrant-looking cells. These are graded by their appearance — how much or how little their appearance deviates from normal prostate tissue. This is the Gleason score, a number ranging from 2-10, with 10 being the most aberrant.
Currently, men with scores of 8 or above are usually advised to get immediate treatment, while those with a score of 5 or below are usually advised to undergo active surveillance. But it's not clear what to do for men whose score is in the middle. And it's also not clear whether biopsies or even the PSA test itself ultimately do more harm than good.
Men with seemingly low-risk prostate cancer currently have two basic choices. Active surveillance is regular testing and monitoring, which can miss the window of catching the rare small but ultimately dangerous cancer when it is easily treatable.
Aggressive treatment, such as surgery or radiation, often has serious side effects. Deciding which choice is best for each case can be difficult and stressful for both doctor and patient.
“Most of the 200,000 prostate cancers diagnosed each year in the U.S. are slow-growing and will remain so, but the three-gene biomarker could take much of the guesswork out of the diagnostic process and ensure that patients are neither overtreated nor undertreated,” said Abate-Shen.
In their quest for a biomarker for slow-growing (indolent) prostate cancer, the researchers focused on genes related to aging, particularly those affected by cellular senescence, a natural phenomenon in which older cells stop dividing but remain metabolically active.
Cellular senescence is known to play a vital role in tumor suppression. After finding 19 candidate genes, they were eventually able to determine that three — FGFR1, PMP22, and CDKN1A — together can accurately predict the outcome of seemingly low-risk tumors.
A larger clinical trial is being planned.
An article on the study appears in Science Translational Medicine.