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Some clinicians who don't recommend AS may simply be slow to change their ways: "In many disciplines, the way you’re trained is the way you treat.”

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Published On January 27, 2020

CLINICAL RESEARCH

The Art of Active Surveillance

Sometimes prostate cancer is best served by a wait-and-see approach. Yet many patients and doctors can't stand the thought of doing nothing. What would change their minds?

WHEN MEN RECEIVE A DIAGNOSIS of prostate cancer, which kills more than 30,000 Americans each year, they tend to be “like deer caught in the headlights,” says Mark Lichty. For his part, Lichty felt terrified and uncertain when he received his diagnosis in 2005 and a urologist recommended removing his prostate.

That procedure, a radical prostatectomy, is standard treatment; a common alternative is to use radiation therapy to destroy the tumor. Yet although both approaches can be effective and save many lives, they can also negatively affect the quality of life. Some two out of three men who undergo prostatectomy and more than half of men whose prostates are irradiated have long-term erectile dysfunction. Surgery causes short-term urinary incontinence in most men, and for one in five, that becomes a long-term condition. And there are persistent bowel problems for one in six patients who get radiation therapy.

Lichty had watched his father suffer what he describes as “gruesome” side effects of treatment in his losing battle against prostate cancer, and Lichty decided he didn’t want to follow suit. He rejected his urologist’s recommendation, choosing instead to put off surgery in favor of what was known then as watchful waiting—having his cancer closely monitored for signs of progression. It was a bold move, and among the medical professionals who urged him to have immediate treatment was his wife, a nurse practitioner. “She thought I was perhaps a bit off the edge,” Lichty says.

But Lichty, who co-founded a support organization called Active Surveillance Patients International in 2018, held firm to his plan, and now, almost 15 years later, routine monitoring shows that his cancer remains in check. I

n the years since Lichty made his decision, the strategy now known as active surveillance (AS) has become much more common. Major medical organizations recommend it as the preferred option for most men with low-risk prostate cancer, who account for about half of all diagnoses. Today some men with somewhat riskier tumors are being offered AS, too. Yet while the proportion of men who choose AS has nearly tripled in the United States since 2010, more than half of Americans who have low-risk prostate tumors still have them treated with surgery or radiation, choosing to live with the accompanying harms despite an equivocal benefit. “If this were like an appendectomy, where you have the operation, you recover and then you’re back to normal, it would be another story,” says University of Toronto urologist Laurence Klotz, an early proponent of AS. “But it’s not like that. To undergo unnecessary radical treatment for a disease that doesn’t pose a threat to the patient’s life is obviously a problem.”

In countries such as Canada and Sweden, the overwhelming majority of eligible men choose AS. Yet although some doctors in the United States have been offering AS as an option since the 1990s, acceptance has been relatively slow. Many patients and their physicians are understandably reluctant to leave a potentially deadly tumor in place, even when the risk is small. Moving more patients to AS may require making better data available to them as well as improving how tumors are detected and assessed for risk. It might also mean changes in how physicians portray AS, a tricky course of treatment that is less a magic pill than a conversation that can last for years.

RESEARCHERS AND CLINICIANS HAVE understood for decades that prostate cancer often poses little risk. When Klotz completed his residency and fellowship in the late 1970s and early 1980s, “it was widely known that low-grade prostate cancer was indolent in many cases,” he says. A few small studies had shown no ill effects in many men whose disease wasn’t treated. And surgeons who performed procedures to address urinary problems caused by enlarged prostates often detected small cancers in the gland—but didn’t raise the alarm. “I was trained to not tell the patient he had cancer,” Klotz says. “We were told to use euphemisms like: ‘We found a few abnormal cells,’” a practice he says was widespread.

The majority of men who did get a cancer diagnosis at the time had incurable disease that was either locally advanced or had spread to other organs. That changed in the early 1990s, however, with the arrival of the prostate-specific antigen (PSA) assay, a blood test that measures levels of a protein that rises when prostate cancer is present.

The test has known flaws: PSA can also rise for other reasons, such as noncancerous inflammation of the prostate, which can cause false-positive results. Yet the test can also catch cancer at an early stage, when it’s likely to be treatable. When the PSA test became available, urologists embraced it as a screening tool, and that led to a surge in prostate cancer diagnoses, the majority of which involved tumors that were small and confined to the gland. Yet in the decade after PSA testing was introduced, more than 90% of those diagnosed with low-grade tumors had radical prostatectomies or radiation therapy.

Like Klotz and a few others, Peter R. Carroll, a surgeon and professor and chair of the department of urology at the University of California, San Francisco, was troubled by that apparent disconnect between the promise of a new cancer screening tool and a surge in potentially unnecessary surgery and radiation. He was one of a small group of clinicians who began suggesting that some men with apparently low-risk cancers could be monitored, at least initially, instead of being sent to the operating room.

It seemed like a logical approach, and in 1995, Klotz and his colleagues began tracking a group of men who chose it. That led many other urologists to condemn what they saw as undertreatment. “I heard statements like, ‘Klotz doesn’t care if his patients die,’” he recalls. “But as the data matured, it became apparent that patients weren’t dying. And they were avoiding a lot of overtreatment.”

Large, long-term studies by Klotz, Carroll and others indeed have shown that men with low-risk prostate cancer who choose active surveillance rarely succumb to the disease. In one 2015 study of 1,298 men, researchers at Johns Hopkins University found that fewer than 1% died of prostate cancer or developed a metastasis over a 15-year period. Moreover, several clinical trials have found that men with low-risk prostate cancer who adopt AS die of prostate cancer about as often as those who receive immediate surgery or radiation—infrequently, in both cases.

As the results of these long-term studies have emerged, AS has become widely accepted, at least officially. The American Urological Association and the National Comprehensive Cancer Network now consider AS the preferred option for people with low-risk prostate cancer. And although criteria for defining low-risk vary, the ideal candidate for AS typically is someone whose tumor is small and confined to the prostate and who has a PSA lower than 10 nanograms per milliliter (ng/ml). That patient also must have had a biopsy of prostate tissue resulting in a score on the Gleason scale—used for gauging how aggressive a tumor may be—of no higher than 6. (Studies have shown that approximately half of prostate cancer diagnosed in the U.S. is Gleason 6 or below.) Guidelines from 2016 suggest that certain patients with intermediate-risk (Gleason 7) tumors could be offered AS, too, though those men are more likely to require treatment eventually, and most U.S. doctors remain uncomfortable with delaying their surgery or radiation.

THEN AGAIN, SOME PHYSICIANS still appear reluctant to offer AS, period. A 2019 study in The Journal of Urology surveyed urology practices across southeastern Pennsylvania and New Jersey and found that although some doctors had all of their low-risk prostate cancer patients in AS, others had as few as 10%. A study in Michigan found that among 30 urologists in one practice, the prevalence of AS ranged from 95% to none.

Some clinicians who don’t recommend AS may simply be slow to change their ways. “In many disciplines, the way you’re trained is the way you treat,” Carroll says, and for some doctors, learning about AS shook the foundation of their medical education. “The idea that you’d find a cancer and not treat it was something both patients and their physicians had a hard time considering,” Carroll says.

In other cases, patients want their doctors to be aggressive about ridding them of cancer. “I believe a lot of overtreatment has been driven by patients, and you can’t blame them,” says biostatistician Andrew Vickers of Memorial Sloan Kettering Cancer Center in New York City, who studies prostate cancer and AS. A meta-analysis of studies that included 7,627 men in AS protocols found that 20% of cases in which monitoring was abandoned in favor of treatment happened “because of patient choice or anxiety.”

Their concern is not out of left field. About one in three men who adopts an AS regimen eventually does get “upgraded,” with follow-up testing indicating a malignancy dangerous enough to warrant surgery or radiation. Informed patients who know these statistics may worry that delaying treatment could make their cancer deadlier (though that doesn’t appear to be true).

But some patients may lack a complete picture, either of the scope of their risks or the process of AS itself. Enrolling a patient relies on a physician navigating a complex conversation that encompasses not only the statistical realities of AS but also questions about quality of life. If the goal is to get more suitable patients into this protocol, then advances need to happen on two fronts: finding more effective ways for a physician to discuss the road ahead, and providing more reassuring data about whether tumors are likely to turn lethal.

PATIENTS MIGHT BE MORE likely to risk AS, for instance, if there were better ways to spot a prostate that does need immediate attention. Biopsies can be hit or miss, with the needles used to retrieve prostate tissue for testing inserted more or less at random. A more effective approach could be to use multiparametric magnetic resonance imaging (mp-MRI) to map where potential tumors might lie. Research shows that mp-MRI targeted biopsies find a greater number of aggressive tumors than standard biopsies, and a study published in JAMA Network Open in September 2019 found that undergoing a pre-biopsy scan can reduce the risk to as low as 8% that a man in AS will need to be upgraded. Study author Leonard Marks, a urological surgeon at the Ronald Reagan UCLA Medical Center in Los Angeles, says he believes mp-MRI should be performed to help guide biopsies in men entering AS programs.

So far, only about one in five prostate biopsies performed in the United States is guided by mp-MRI, Marks estimates. One reason it’s not more widely used may be the expense, which some insurance companies don’t cover. Another issue: “Performing and interpreting a prostate MRI requires advanced training, which many radiologists lack,” he says.

Newly available genetic tests that gauge whether a prostate tumor is likely to spread and turn deadly might also help, and several studies have shown that these tests are beginning to influence men’s decisions about whether to choose AS. According to the University of Toronto’s Klotz, however, the tests are likely to be most valuable for men with intermediate-risk tumors who are on the fence about AS. “These tests definitely have a role, but it’s for a minority of patients,” Klotz says.

Other kinds of innovations might help physicians convey the advantages of AS. Vickers and several colleagues at Sloan Kettering, including surgeon Behfar Ehdaie, collaborated with Deepak Malhotra, a professor at the Harvard Business School and an authority on negotiation, to develop a systematic approach to counseling patients that uses principles from the behavioral science of decision-making. For example, social scientists know that when people aren’t sure how to behave, they tend to look at what their peers typically do. So if a good candidate for AS is agonizing over his decision, a physician might advise the patient that AS is the choice of most of that doctor’s patients who have low-risk prostate cancer. “We can talk about why you might be different, and I’ll explain the other options,” the doctor might say, “but you should know that’s what most men do.” In a 2017 study published in European Urology, Vickers and his colleagues showed that using this and related techniques increased the proportion of men in their clinic who chose AS by 9 percentage points—a change that reduced overtreatment by 30%, according to their calculations.

A more radical proposal is to change the way low-risk malignancies in the prostate (and elsewhere, including the breast and thyroid) are discussed. “Patients report their anxiety skyrocketing when they hear the word ‘cancer’; they feel a sort of mental paralysis that stops them from hearing anything else,” says Kirsten McCaffery, who studies health literacy at the University of Sydney School of Public Health in Australia. McCaffery’s research shows that people who are told they have “lesions or abnormal cells” rather than cancer are less likely to opt for unnecessarily aggressive treatment.

THE MOVE TOWARD GREATER acceptance of active surveillance has played out against a different, though related, conversation about the advisability of screening for prostate cancer at all. In 2012, the United States Preventive Services Task Force (USPSTF), an advisory panel, recommended that men skip the PSA test, because the panel’s research showed that the test’s downsides—particularly its knack for identifying meaningless tumors that may prompt aggressive treatment and its accompanying harms—outweighed its benefits. But in 2018, the USPSTF softened its stance, recommending that men ages 55 to 69 should talk to their doctors and decide for themselves whether to have the test. A primary reason for the change of position, the panel noted, was that more men were enrolling in AS regimens. That meant fewer men were being needlessly harmed by a PSA-aided cancer diagnosis.

Klotz says he hopes the trend of more men opting for AS will “rehabilitate” PSA screening, which he believes is valuable. The test often detects deadly tumors as well as harmless ones, and when the USPSTF recommendation led to lower rates of screening, higher numbers of men began to be diagnosed with advanced disease. And death rates from prostate cancer, which had been falling for years, flattened. Having AS as an option can make prostate cancer screening more appealing, and if more men choose it, more serious tumors are likely to be caught in time for life-saving treatment. “Reducing the burden of treatment for a lot of these patients,” Klotz says, “could ultimately result in a decrease in prostate cancer mortality.”

DOSSIER:

Active Surveillance for Prostate Cancer: How to Do It Right,” by Juan D. Garisto and Laurence Klotz, Oncology, May 2017. The authors, who include an AS pioneer, offer an evidence-based rationale for this treatment approach and guidelines for administering it.

Active Surveillance for Low-Risk Prostate Cancer in Black Patients,” by Brandon A. Mahal et al., The New England Journal of Medicine, May 2019. This letter examines recent trends in the use of AS in black men with low-risk prostate cancer.

Renaming Low Risk Conditions Labelled as Cancer,” by Brooke Nickel et al., BMJ, August 2018. In this paper, the authors argue that removing the “cancer” label from low-risk prostate malignancies, as well as rarely lethal forms of other cancers (such as breast and thyroid), could reduce overdiagnosis and overtreatment.