Patients With Bladder Cancer May Avoid Removal of Extra Lymph Nodes, Study Finds
For years, doctors have thought that a more extensive surgery that removes a wider swath of lymph nodes was the best option for certain patients with bladder cancer. Now, a new clinical trial is upending that belief.
Researchers found that the strategy — known as extended lymphadenectomy — was no better than standard surgery at prolonging patients' lives or the amount of time they lived free of a bladder cancer recurrence. What's more, it increased their risk of complications like blood clots, serious infections and death within 90 days of surgery.
Experts said the long-awaited results, from a clinical trial begun over a decade ago, will likely change many surgeons' practice.
At the center of the issue are patients with muscle-invasive bladder cancer — where the cancer has spread past the inner lining of the bladder and penetrated the muscle tissue of the bladder wall. That raises the chances that tumor cells have escaped to lymph nodes just outside the bladder, or beyond.
In the United States, more than 83,000 people are diagnosed with bladder cancer each year, and about 25% have muscle-invasive cancer, according to the American Urological Association.
Those patients typically have the whole bladder surgically removed, along with other pelvic tissues — including nearby lymph nodes that might contain tumor cells.
But at many hospitals, surgeons have been doing extended lymphadenectomy procedures for years — taking out additional nodes, farther up into the abdomen. That was based on studies showing that patients' survival tended to improve when a greater number of lymph nodes was removed.
The approach "has become increasingly embedded in our teaching," said lead investigator Dr. Seth Lerner, chair of urologic oncology at Baylor College of Medicine, in Houston.
What's been lacking is a "gold standard" clinical trial to rigorously test whether the extended strategy is really more effective than standard pelvic node removal. Lerner and his colleagues are now reporting on just such a trial, funded by the U.S. National Institutes of Health.
And the verdict is: Extended lymph node removal is not the better procedure after all.
The trial involved 618 patients at 27 medical centers in the United States and Canada. All were undergoing a radical cystectomy (complete bladder removal) for muscle-invasive bladder cancer.
During the procedure, the patients were randomly assigned to have either standard removal of the pelvic lymph nodes or extended node removal.
Patients in the extended group had substantially more nodes removed — typically around 39, versus 24 in the comparison group. Still, they were no more likely to have their lymph nodes test positive for cancer spread.
Nor did they fare any better over the next six years, the trial found. Patients in both treatment groups had similar overall survival and disease-free survival — the amount of time they lived free of a cancer recurrence. The actual survival figures were not reported.
There were some numbers on harms, though. Over 90 days, more patients in the extended lymphadenectomy group died: 19, versus seven in the standard surgery group.
They were also more likely to have side effects like blood clots and sepsis — a potentially life-threatening complication of certain infections. In all, 49% of patients in the extended group and 42% in the standard group had some kind of serious side effect.
Lerner presented the findings Monday at the American Society of Clinical Oncology's annual meeting, in Chicago. Findings released at meetings are generally considered preliminary until they are published in a peer-reviewed journal.
Why wasn't the extended strategy the better choice?
Lerner said it's not clear, but he noted that muscle-invasive bladder cancer is a curable disease. And patients often not only receive surgery, but — if they're healthy enough to tolerate it — chemotherapy. More than half of the trial patients received pre-surgery chemo.
Lerner said it's also possible that many patients were cured after their surgery, and taking out additional lymph nodes made no difference.
The bottom line, he said, is that for patients like those in the trial, there is no reason to use the extended strategy.
A bladder cancer specialist who was not involved in the trial agreed that the findings should change practice.
"A lot of people thought this would be a better technique," said Dr. Scot Niglio, an oncologist at NYU Langone's Perlmutter Cancer Center, in New York City.
It made sense that removing more nodes might improve patients' outlook. "But," Niglio said, "this shows that just because we can doesn't mean we should."
The good news, both doctors said, is that muscle-invasive bladder cancer is treatable, and more options have become available in recent years. Patients whose cancer has a high risk of coming back, for example, may receive immunotherapy — drugs that enlist the immune system to battle the cancer.
But relative to other common cancers, bladder cancer does not get much attention. "It just doesn't get talked about a lot," Niglio said.
One important point about the disease, he noted, is that the primary controllable risk factor is smoking. So, it's yet another reason for smokers to quit.
As for symptoms of the disease, blood in the urine is often the first. That can also be a sign of many other conditions, Lerner said, and people should see their doctor to get to the bottom of it.
The Bladder Cancer Advocacy Network has more on muscle-invasive bladder cancer.
SOURCES: Seth Lerner, MD, chair, urologic oncology, professor, urology, Baylor College of Medicine, Houston; Scot Niglio, MD, medical oncologist, Perlmutter Cancer Center, NYU Langone, assistant professor, medicine, NYU Grossman School of Medicine, New York City; June 5, 2023 presentation, American Society of Clinical Oncology annual meeting, Chicago