en diagnosed with early prostate cancer can safely choose active monitoring rather than surgery or radiation without cutting their lives short, according to an eagerly awaited landmark study published on Wednesday.
Although research dating back to the 1970s has hinted that many prostate cancers are too slow-growing to threaten a man’s life, the new study is the most definitive ever to test that premise. It is also the first to compare modern forms of active monitoring not only to surgery but also to radiation — the two treatments available for early, localized prostate cancer.
Experts unanimously hailed the bottom line: Men who received active monitoring had the same minuscule risk of dying of prostate cancer over the following 10 years — barely 1 percent — as men who underwent surgery to remove the prostate or radiation. “Virtually no one had died from prostate cancer,” said Dr. Mark Litwin, chair of urology at the David Geffen School of Medicine at UCLA, who was not involved in the research. “That is a really striking finding: All three groups have almost 100 percent surviving. That should give all men pause before pursuing radical treatment for low- or intermediate-risk tumors.”
With active monitoring, cancer can continue to grow within the prostate or even spread beyond it. The study found that metastasis was twice as likely to happen in the untreated group. But even that did not put the patients at greater risk of dying, at least during the decade that they have been followed by researchers at the University of Oxford. “If the cancer spreads or progresses” in men who selected active monitoring, “we just pull the trigger” and begin treating it, said oncologist Dr. Marc Garnick of Beth Israel Deaconess Medical Center in Boston, who specializes in prostate cancer and was not involved in the study. That occurs in about half of patients, he said.
The findings, published in the New England Journal of Medicine, are in line with many other studies, including one last year which found that men who opted for active surveillance had about the same risk of dying of their disease over the 15 years after diagnosis as men who chose to be treated.
But those were mostly observational studies, in which men chose what treatment, if any, to undergo. In the new study, 1,643 men diagnosed (via blood test) with localized prostate cancer who volunteered for the “ProtecT” clinical trial starting in 2001 were randomly assigned to one of three groups: active monitoring, surgery to remove the prostate, or radiation plus a short course of hormone-deprivation therapy. Such randomization produces more reliable results, minimizing the chance that men who chose monitoring were different — healthier — than men who chose treatment.
In active monitoring, men with localized prostate cancer (it has not spread beyond that organ) do not get surgery or radiation right after they’re diagnosed. Instead, they have regular biopsies, blood tests, and MRIs to see if their cancer is progressing. If it is, they can receive treatment.
Although some oncologists advise men with early, low-grade prostate cancer to choose active surveillance — and professional groups such as the American Society of Clinical Oncology recommend it — many patients recoil at what sounds like “let’s just wait for your cancer to become really advanced.” A decade ago fewer than 10 percent of men diagnosed with prostate cancer chose monitoring, UCLA researchers found. But that is changing. Now at least half of men do.
That made sense to Garth Callaghan, author of the best-selling Napkin Notes, a book of missives he tucked into his daughter’s lunch box. Diagnosed with early prostate cancer in 2012, he said, “none of the choices seemed particularly attractive to a 43-year-old man” who dreaded the possibility of side effects of surgery or radiation, including incontinence and impotence. “I was completely torn. My previous experience [with illness] was, just get it out of my body.” But after his doctor explained that prostate cancer is grossly overtreated in the United States, “I did a complete 180” and chose active monitoring.
And if the cancer progresses or spreads beyond his prostate? “We can treat it then,” Callaghan said.
The study shows that “you have no business treating low-grade prostate cancer in someone with a life expectancy of less than 15 years” because the side effects outweigh any benefits, said urological surgeon Dr. Peter Albertsen of the University of Connecticut Health. The Oxford scientists reported that 46 percent of men who had their prostate removed were using adult diapers six months later (versus 4 percent in the monitoring group). Similarly, only 12 percent of men who got surgery and 22 percent who had radiation could sustain an erection, compared to 52 percent of the monitoring group.
An estimated 180,890 men in the US will be diagnosed with prostate cancer this year, according to the American Cancer Society. Some 26,120 will die of it in 2016, almost always because it has spread to a vital organ.
In an editorial accompanying the study, radiation oncologist Dr. Anthony D’Amico of Brigham and Women’s Hospital focused on the finding that men who opted for monitoring were more than twice as likely to develop metastatic prostate cancer. That is, malignant cells reached the bones, lung, liver, or brain.
But the actual numbers were very small. Among the 545 men receiving monitoring, 33 eventually developed metastatic disease; of the 553 who had their prostate removed, 13 did; of the 545 who had radiation therapy, 16 developed metastases. The treatment groups also had lower rates of disease progression, meaning that the cancer became more aggressive or grew: that happened to 46 men who got surgery, 46 who had radiation, and 112 who had only monitoring.
“If you are a man in excellent health, with a life expectancy greater than 10 years, these data say if we continue to [just] watch over you, you are twice as likely to develop metastatic cancer,” D’Amico said. “That requires hormone treatment” — androgen deprivation therapy that starves prostate cancer cells — “for the rest of your life, which essentially causes chemical castration and can make life miserable.”
But one-quarter of the men in the study had intermediate-risk cancer, not low-risk, and it is the latter to whom most doctors suggest active monitoring, said Dr. Laurence Klotz, a veteran prostate cancer researcher at Toronto’s Sunnybrook Health Sciences Center. “It’s not surprising this group, therefore, had a higher metastasis rate, but that should not be generalized to low-risk patients.”
Garnick agreed: The intermediate-risk men “we would never assign to active monitoring.” If the increased metastases came from these patients, “it would explain those differences and even more strongly encourage the role of active management” in truly low-risk prostate cancer.
The conflicting conclusions that experts draw from the same data reflects the fact that the cancer world “is rather polarized,” said epidemiologist Jenny Donovan of the University of Bristol, who helped lead the study. But with the nearly 100 percent rate of survival with treatment or monitoring, “men do not need to rush to make a decision about treatment.” Instead, they should weigh the chances of disease progression and side effects, “and make a choice that suits their views about their quality of life and current or likely future health concerns.”