Dec. 14, 2021 -- It’s a question that has divided men’s health experts for years: Should healthy men, with no symptoms or family history of prostate cancer, get a prostate specific antigen test and treatment right away if a tumor is found?
Men’s health experts and cancer specialists say the continuing back-and-forth on PSA testing and active surveillance has deepened widespread confusion for men with questions about what to do.
Proponents of routine PSA testing say it is the best screening tool in oncologists’ arsenals for catching prostate cancer early, when it is most treatable.
But opponents argue that it prompts many newly diagnosed men to seek invasive treatments that can cause impotence and incontinence, although up to 80% have low-risk tumors that will never be life-threatening. For them, they say, the best option is “active surveillance,” where doctors monitor patients closely for signs their cancer is advancing before treating it.
This fall, the influential National Comprehensive Cancer Network (NCCN) reignited the debate, recommending active surveillance, surgery, or radiation for men newly diagnosed with prostate cancer as a result of PSA testing -- giving equal weight to all three approaches.
After a firestorm of criticism, the NCCN reversed course and now recommends that “most men” with low-risk prostate cancer be managed through active surveillance as the “preferred” first treatment option over surgery and radiation.
The updated guidelines also reiterated the group’s stance against routine PSA testing for most men “as a general population screening tool due to its well-documented limitations” and its potential for prompting overtreatment.
Some oncologists even say the debate has eclipsed the most important point about prostate cancer -- that each case requires a personalized, patient-centered approach to testing and care that one-size-fits-all screening guidelines don’t take into account.
“These guidelines are always changing back and forth, and I’ve seen a lot of these changes,” says David Samadi, MD, a urologic oncologist and director of men’s health at St. Francis Hospital in Roslyn, NY. “But individualized care is the best way to go.”
He says men should work with their doctors to determine whether and when to have PSA testing, based on their unique genetic and biological makeup, age, family history, overall health, lifestyle, race, ethnic background, and other factors. Any course of cancer care should be approached in a similar, patient-centered way, he says.
Otis W. Brawley, MD, a professor of oncology and epidemiology at Johns Hopkins University, agrees that PSA testing is an important screening tool, but it should not always lead to treatment. Men need to weigh the risks and benefits of testing and understand that most diagnosed with prostate cancer should not be rushed to surgery, radiation, or other therapies, he says.
“Given the uncertainty that PSA testing results in more benefit than harm, a thoughtful and broad approach to PSA is critical,” Brawley says, citing the current position of the American Urological Association.
“Patients need to be informed of the risks and benefits of testing before it’s undertaken. The risks of over detection and overtreatment should be included in this discussion.”
Brawley says his own position on PSA testing has evolved over the past 3 decades, in part because most men are no longer routinely treated aggressively at the first sign of cancer.
“I was very much against screening for prostate cancer, especially in the 1990s,” he says. “Fifteen years ago, every man who was found to have localized prostate cancer in the United States, if he was diagnosed on a Tuesday or Wednesday, he was told it needs to be out of your body by Friday, week after next, literally.
“Now, there are areas of the United States where half of all men with screen-detected prostate cancer are watched and most of those men will never be treated for their prostate cancer.”
PSA Testing: Pros, Cons
A PSA test measures blood levels of prostate-specific antigen, which can be high when cancer is present in the prostate, the walnut-sized gland that produces seminal fluid and is key to a man’s sexual functioning.
The test was introduced in 1994 to detect the possible presence of prostate cancer, the second-leading cause of cancer deaths in American men. A PSA level of less than 4 nanograms per milliliter of blood is considered normal; when it spikes to 6 or higher in a year’s time, doctors are likely to suggest a biopsy to check for a tumor.
If prostate cancer is seen on a biopsy, PSA levels can be used to determine the stage of cancer -- how advanced it is. Cancers are also assigned a grade -- called a Gleason score -- that can show how likely it is to spread. Gleason scores of 6 or less are considered “low grade,” 7 is “intermediate,” and 8 to 10 is “high grade.”
But PSA testing is not foolproof. Cancer isn’t the only thing that can raise PSA levels. Inflammation, infection, and an enlarged prostate (common in men over 50) can cause increases in PSA. So it’s not as accurate a cancer predictor as, say, genetic tests for the BRCA1 and BRCA2 genes strongly linked to breast cancer (and a very small number of prostate cancers).
Even when testing turns up a tumor, it does not indicate whether it’s an aggressive form of cancer that needs treatment right away or is a slow-growing, low-risk tumor unlikely to be life-threatening. In fact, autopsy studies have found that undiagnosed prostate cancer is found in about a third of men over 70 who die from some other cause.
But there is no question that PSA testing has helped identify many cancer cases that might otherwise have not been found in early stages. Research shows:
- PSA screening can flag cancer about 6 years earlier than a digital rectal exam and 5-10 years before symptoms of the disease emerge.
- The death rate from prostate cancer has fallen by more than half since the FDA first approved PSA tests.
- Nine in 10 cases in the U.S. are found while the disease is confined to the gland (or nearby), when nearly all men with the disease survive 5 or more years.
- About 4 out of 5 men with an elevated PSA who are found on biopsy to have cancer have a low-risk form of the disease that is unlikely to kill them before something else does.
Even so, the doubts about PSA testing have led to widespread debate over who should have it done, at what age, and how doctors and patients should respond to an elevated level.
“Not everyone needs to be screened, not everyone found to have an elevated PSA needs to be biopsied, and Lord knows that not everyone with prostate cancer needs aggressive treatment,” said Colorado Springs urologist Henry Rosevear, MD, writing in Urology Times.
In the face of the uncertainties, men have to weigh competing and confusing advice on PSA testing and active surveillance.
- The American Cancer Society recommends that men with at least a 10-year life expectancy “make an informed decision” with their doctor about PSA testing. Discussions should begin at age 50 for men at “average” risk for cancer, 45 for those at “high risk” (African Americans and men with a father, brother, or son diagnosed with the disease before 65), and 40 for “higher risk” people (with more than one close relative diagnosed with prostate cancer at an early age).
- The National Comprehensive Cancer Network does not endorse routine screening but advises men 45 to 75 years old to discuss screening risks and benefits with their doctor.
- The American Urological Association recommends that men 55 to 69 years old weigh the risks and benefits of PSA screening and advises against testing for men under 40, those between 40 and 54 at “average risk,” and men over age 70 or with “a life expectancy less than 10-15 years.”
- In 2018, the U.S. Preventive Services Task Force (USPSTF) revised its controversial 2012 recommendation against prostate cancer screening and now advises that for men ages 55 to 69, “the decision of whether or not to undergo screening should be individualized.” For men 70 and older, the USPSTF recommends against PSA testing.
Samadi says tracking PSA levels and trends over a period of years or decades is far more valuable than a single isolated test result, when it comes to assessing a man’s cancer risk and how best to handle it.
“I’m a big proponent of PSA screening and … I always tell the patients to get a baseline PSA at the age of 40,” he says. “And if that’s absolutely normal, then you can repeat it every 2 or 3 years.”
But from the get-go, Samadi says, it’s important to understand that an elevated PSA test, on its own, does not necessarily mean any man needs surgery, radiation, or other treatment right away that can affect his quality of life.
Brawley agrees, noting that studies show a prostatectomy (surgery to remove all or part of the prostate) carries a 40% risk for impotence and/or urinary incontinence and a 0.5% chance of dying from the operation, while pelvic radiation can lead to bladder and bowel irritation and bleeding.
“A large number of men who are screened and who are diagnosed with prostate cancer today are going to be told you have one of the more benign-ish prostate cancers -- yes, it’s malignant, but it’s less aggressive,” he says. “Therefore, instead of giving you a radical prostatectomy [or] radiation … we’re going to watch you.”
Advances in Biomarkers, Genetics
In recent years, researchers have been working to develop more refined and sophisticated techniques than PSA testing to help identify more aggressive tumors early, reports James Eastham, MD, of Memorial Sloan Kettering Cancer Center in New York City.
One is the so-called 4Kscore test that assesses the levels of four prostate-specific antigens to gauge a man’s risk of having an aggressive cancer.
Another, called the prostate health index, combines three PSA measurements to identify cancer and help some men avoid a biopsy.
A third test, ExoDx Prostate IntelliScore, examines biomarkers in urine to help predict a man’s likelihood of having prostate cancer that will spread and become deadly without treatment right away.
Researchers are also studying an advanced form of MRI that can detect higher-risk prostate cancers.
In addition, other newly developed tests and methods -- some based on molecular and genetic tests -- are showing promise.
Samadi says these personalized, next-wave tests are more precise tools that go beyond PSA testing to help guide oncologists’ decisions on care, management, and treatment of their patients.
Maurie Markman, MD, a medical oncologist, believes this new breed of genetic tests and molecular biomarkers will revolutionize cancer therapy.
“As time goes on, there will be molecular markers that will be discovered that will help refine this [to] actually predict with a much higher precision those patients who will develop high-grade cancer or metastatic disease much better than PSA or Gleason score,” says Markman, president of medicine and science at the Cancer Treatment Centers of America. “That’s the future.”
Improvements in Treatment
Samadi says some of these advances have already improved prostate cancer detection and will continue to do so.
But at the same time, vast improvements have been in made in how doctors perform biopsies and treat cancer with surgery, radiation, chemo, or hormone therapy (known as androgen deprivation therapy), he says.
Major strides have been made in surgical techniques (using less invasive laparoscopic and robotic-assisted techniques), digital medicine (using MRI and other scans), and more targeted radiation therapy. Meanwhile, clinical trials are underway for new drugs designed to treat genetic factors that drive cancers of all types.
Samadi says he’s also seen major progress in treating prostate cancer as a result of changes in American medicine since the 1990s.
“When I was in training in residency, 25-30 years ago, we would see people coming in with hard-rock prostates, and we were doing a lot of surgery, chemo, hormonal treatment, and radiation,” he notes. “But over the course of the last 3 decades, a lot has changed, and [it] all happens to be good.”
For one thing, an elevated PSA no longer triggers the “knee-jerk reaction” that a biopsy must be done, and immediate treatment be sought if a tumor is uncovered.
And advances in MRI technology now allow doctors to use imaging -- instead of surgical biopsies -- to assess prostate tumors.
Twenty years ago, urologists would randomly biopsy six or more areas of the prostate in a hit-or-miss hunt for tumor cells that often required patients to have multiple procedures.
“But today, we’re using more of a targeted biopsy, we’re finding out where the lesion is, we go straight into the lesion, and we’re able to find out exactly what the cancer is,” Samadi says. “So it’s less invasive, less headache, more targeted, and more intelligent.”
Radiation techniques have also improved over the past 2 decades.
In the 1900s and early 2000s, full-pelvis radiation was common, often causing serious complications. But more precise radiation techniques -- involving “CyberKnife” therapy and proton therapy -- can now be used to deliver tiny, precisely aimed beams of radiation into tumor cells, sparing healthy surrounding tissues and reducing complication risks.
Cancer specialists are also optimistic about the promise of other therapeutics now in the pipeline.
Early research has found, for instance, that cutting-edge prostate-specific membrane antigen (PSMA) scans can identify high-risk cancers. These scans use radioactive tracers that attach to PSMA, a substance often found in large amounts on prostate cancer cells, and are now being used in some medical centers.
Another technique -- called “radioligand therapy,” already approved overseas -- combines a targeting compound that binds to cancer biomarkers to enable precisely targeted delivery of radiation to the tumor, leaving healthy surrounding tissue unharmed.
In addition to these advances in treatment options, Samadi says the approach to treating prostate cancer -- particularly in older men -- has undergone a sea change. Twenty years ago, men older than 70 were not considered good candidates for surgery or other treatment, he says.
“But that concept doesn’t make sense anymore today, and the reason is medicine has improved … and we see a lot of people in their 80s and 90s,” he says.
For instance, Samadi says some of his patients are 70 and older who are healthy, physically fit, and great candidates for surgery because they are likely to live many more years. On the other hand, he treats patients in their 50s who are obese, diabetic, and/or have heart disease who aren’t likely to benefit as much from prostate surgery.
“I look at my patients individually,” he says. “If they are healthy and they are in good physical shape and I think they would be an excellent candidate in the operating room under my care, then I know this guy can be cancer-free with our robotic surgeries and with good continence rate and good sexual function, etc.”
The upshot: As more men are living longer with prostate cancer as a result of improvements in diagnostics, surgery, radiation, and other advances, treatment decisions should not be based on age, PSA test results, or other single-factor considerations alone.
“A one-size-fits-all approach is not a good treatment plan,” Samadi says. “Individualized care is the best way.”