Most patients diagnosed with early-stage prostate cancer will live just as long if they simply watch their cancers rather than have them surgically removed, according to the results of a landmark clinical trial that could upend the medical approach to a disease that affects 1 in 6 men.
The study, which focused on cancers still confined to the prostate, should reassure patients who want to avoid distressing side effects of surgery – such as urinary incontinence and sexual dysfunction – but still protect their lives, cancer experts said. If embraced by patients and doctors, the new information stands to radically change prostate cancer management in the U.S., where the majority of early prostate cancers are treated aggressively with surgery or radiation therapy.
The much-anticipated results of the so-called PIVOT trial, reported in Thursday’s edition of the New England Journal of Medicine, did find that surgery provided a slight benefit for patients with higher-risk early cancers. That group included men whose blood levels of prostate-specific antigen, or PSA, were above 10 nanograms per milliliter or who had larger tumors with cells that were more abnormal in appearance.
And because the average age of the 731 men who participated in the trial was 67, with only 10% under age 60, the implications for younger men who have more potential years ahead of them are less certain, experts noted.
But overall, the clinical trial – the largest of its kind and the first in the era of widespread PSA screening – should be welcome news for men diagnosed with early prostate cancer, said Dr. Mark S. Litwin, chair of urology at UCLA and a researcher at the university’s Jonsson Comprehensive Cancer Center.
“The trial gives us results that we have been waiting for in urology for quite some time,” said Litwin, who was not involved in the study. “It confirms many of the recent reports that men with prostate cancer, by and large, can be safely managed with close monitoring.”
The conclusions may well overstate the benefit of surgery, said study leader Dr. Timothy J. Wilt, a specialist in disease prevention and health promotion who works at the University of Minnesota and the Minneapolis Veterans Affairs Health Care System.
That’s because only about half the men in the trial discovered their tumors through PSA tests, which are more common today than they were when men joined the trial, starting in 1994. In addition, doctors at the time would wait for higher PSA levels before ordering biopsies.
As a consequence, men in the past often had larger tumors by the time their prostate cancers were found.
“Men diagnosed today will likely have an even better prognosis with observation,” Wilt said.
An estimated 241,740 new cases of prostate cancer will be diagnosed in the U.S. this year, and 28,170 men will die of it, according to the American Cancer Society. It is the second-leading cause of cancer death in men, after lung cancer.
Men in the trial were recruited from 44 Department of Veterans Affairs medical centers across the U.S. and eight medical centers that earned special recognition from the National Cancer Institute. Patients were randomly assigned either to receive surgery or to forego treatment and have their cancers followed with checkups every six months.
In the observation group, symptoms such as difficulty in urination or cancer that spread to the bones were treated as they arose.
About half of the men – who were tracked for a median of 10 years – died during the course of the study. But the vast majority of these deaths were not from prostate cancer, the authors noted. That finding underscores the often-repeated saying among urologists that more men die with prostate cancer than of it.
The likelihood of death from any cause was the same for patients who had surgery and those who didn’t. Surgery did not affect mortality rates for any subgroups based on race, age or overall health status.
Only 7.1% of men in the study died from prostate cancer or as a result of surgery to treat it, in statistically equal numbers in both groups.
“That’s a key point” that men should absorb, said Dr. Durado Brooks, director of prostate and colorectal cancers for the American Cancer Society. “When most men are told they have prostate cancer, their immediate thought is, ‘Oh my God, I’m going to die,’ and their immediate next step is, ‘Let’s do something about this.’ ” By then, Brooks said, “the idea of an observation approach is lost.”
That is significant, because the consequences of surgery are not benign. Twenty-one percent of men in the study experienced complications such as wound infection in the 30 days after surgery, and one man died. After two years, rates of urinary incontinence and erectile dysfunction were roughly twice as high in the surgery group compared with the observation group.
Though all of the men had a diagnosis of early prostate cancer with no spread to the bones, there were differences in the seriousness of those cancers. Some of the tumors were larger, some men had higher PSA levels, and some had higher so-called Gleason scores, numbers assigned to cancers based on how abnormal the cells look under a microscope.
When higher-risk cancers were assessed separately, the authors detected a slight edge with surgery, most clearly in those men with PSA scores over 10 nanograms per milliliter of blood. Among these patients, death from any cause was 13% lower in the surgery group and death related to prostate cancer was 7% lower compared with the observation group. Men who had surgery were also half as likely to see their cancer spread to the bones, which produces pain that is hard to manage and raises the risk of fractures.
For high-risk men, “surgery clearly has been shown to be beneficial over watchful waiting,” said study coauthor Dr. William Aronson, a urologist at the VA Greater Los Angeles Healthcare System.
Even so, experts noted, men in this category who are older or who have significant other health issues might consider observation or a more hands-on approach called active surveillance – in which PSA tests and biopsies are taken periodically and treatment is begun if the cancer appears to be spreading – because they are still more likely to die of something other than their prostate cancer.
Another factor to consider is a man’s personality and priorities, said 73-year-old prostate cancer survivor Jim Kiefert of Olympia, Wash., a member of the prostate cancer support organization Us Too.
Some men in the support group he leads – especially younger men – will welcome the study’s news because they greatly fear the side effects of surgery, he said. But it will be a hard sell to many others, he added.
“You have to be psychologically stable enough to say, ‘Look, I’ll let that cancer stay in me. If it starts to grow, I’ll do something about it. But if not, I’ll just go on with my life.’ “
The trial did not compare observation to radiation therapy, another common treatment for localized prostate cancer. But scientists said the outcome is unlikely to differ.
By Rosie Mestel, Los Angeles Times