‘A call to arms’: Addressing the undertreatment of advanced bladder cancer
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For decades, the 5-year survival rate for patients with advanced bladder cancer has remained at about 35%.
This standstill might suggest a lack of effective treatment options, but data suggest otherwise: a 2018 study showed 79% of patients who underwent radical cystectomy and 69% of those treated with trimodal therapy survived at least 10 years.
According to Ralph de Vere White, MD, UC Davis Health distinguished professor emeritus, the reason for this disparity is undertreatment, particularly of muscle-invasive bladder cancer.
De Vere White and colleagues reviewed data from several studies and found that more than half of patients with muscle-invasive bladder cancer received no treatment with curative intent. Their paper was published in Journal of Clinical Oncology and has been endorsed by the Society of Urologic Oncology.
“It’s a call to arms,” Harry W. Herr, MD, urologic oncologist at Memorial Sloan Kettering Cancer Center, told Healio. “I agree [with the paper] that urologists need to be more aggressive and recognize the seriousness of this disease. Untreated bladder cancer is a disaster. It kills patients in 18 months, and they don’t live very well. They have a bad existence.”
Not just a U.S. problem
In their paper, de Vere White and colleagues cited one study of 28,691 patients with muscle-invasive bladder cancer in the National Cancer Database that showed only 41.3% underwent radical cystectomy and 7.6% received definitive radiotherapy. When analyzed by age, the researchers found that 64% of patients aged 50 years and younger underwent radical cystectomy, and 15% received surveillance. Similar proportions of patients aged 61 to 70 years underwent radical cystectomy (60%) and surveillance (19%).
A separate study by Gore and colleagues assessed 3,205 Medicare patients with stage II (organ-confined, nonmetastatic) bladder cancer in the SEER database. Among them, only 21% underwent radical cystectomy, resulting in a 5-year OS rate of 42%. In contrast, the 51% of patients who received surveillance had a 5-year OS rate of 14.5%.
De Vere White and colleagues attributed the differences in the results of the two studies to the fact that 80% of patients in the National Cancer Database receive treatment at teaching/research hospitals affiliated with medical schools and/or NCI-designated cancer centers, whereas SEER is more representative of the general U.S. population.
Studies of non-U.S. populations yielded similar findings. In an analysis of Sweden’s national Bladder Cancer Database between 1997 and 2014, researchers found no improvement in overall mortality or cancer-related mortality over time among patients with bladder cancer. Additionally, 55% of men and 62% of women with nonmetastatic muscle invasive bladder cancer received no treatment with curative intent during the study interval. Patients with stage T2 bladder cancer treated without curative intent had median OS of 12 months, and those with T3 disease treated without curative intent had median OS of 9 months.
“Sweden and the U.S. have very, very different health care systems,” de Vere White told Healio. “You could even say they have very different philosophies in life, and yet we have the same findings. I think when you look at this, it’s incontrovertible that in America, half of the patients who have the most curable form of muscle-invasive bladder cancer are not receiving treatment intended to cure their disease.”
Factors involved
The low rates of standard-of-care radical cystectomy among this patient population can be explained by various factors, according to de Vere White and colleagues, who sought to identify some of the most prominent reasons.
Those mentioned in the SEER study included age of the patient, comorbidity and travel distance to a treatment center.
However, de Vere White and colleagues wrote that it “stretches credulity” to believe that of the 348 patients aged 66 to 69 years, 125 were deemed too ill to receive treatment with curative intent.
“For one thing, age is likely not the main issue; these patients were in the same age group,” de Vere White told Healio. “The second thing is that it is not believable that in the 66- to 69-year-old age group, the comorbidity was so bad that the number of patients not treated with curative intent equaled the number who had cystectomies.”
Herr agreed that age and comorbidity do not fully explain the low rates of curative-intent treatment among these patients.
“These patients are elderly and they’re getting older, because bladder cancer is a disease of advanced age,” he said. “Patients also tend to have comorbid conditions and are often frail or nutritionally compromised, so aggressive treatment is difficult. But that is not the major reason.”
The third reason cited in the SEER study was the travel required for patients to access a treatment center. The study reported that the chances of receiving radical cystectomy declined by 40% if a patient had to travel 50 miles or more to a center.
De Vere White said regardless of whether the patient received radiation therapy, radiation with neoadjuvant chemotherapy, neoadjuvant chemotherapy and cystectomy, or cystectomy, the visit to a Center of Excellence would likely entail more than an overnight stay.
“The median age for this disease is 72 [years],” he said. “Think about this for a second. You’re 50 miles away from a center that does those treatments. In 2018, 60% of Americans said they did not have $1,000 worth of savings that they could utilize for a major emergency.”
He also mentioned the time investment involved, and the need to enlist adult children for transportation or accompaniment.
Herr said issues of location and travel are particularly relevant in the United States, which is geographically large, sprawling and rural compared to Europe. He added that urologists at community hospitals may not feel prepared to undertake cystectomy.
“The main barrier that I see is that the urologist may or may not see the patient, and when they do see the patient, may not be prepared to do major surgery that has high morbidity — or may not have hospitals available to take care of patients requiring intensive care,” Herr said. “Or maybe they don’t want to do the surgery because they’re not equipped, or it’s too difficult. The complication rate is high; reimbursement is low.”
The paper reported the following rates within 90 days after radical cystectomy at Centers of Excellence: major complications, 24%; ED visits, 38%; readmissions, 30%; and death, 4%. Patients who undergo radical cystectomy at major centers may be treated for complications and recover at local hospitals. Because these hospitals often have less experience in dealing with these complications, these patients may have worse outcomes.
Possible solutions
De Vere White said for this situation to improve, clinicians at Centers of Excellence need to work with physicians at community hospitals to provide consultation and guidance in the treatment of these patients.
“The first thing we have to do is build and ensure true cooperation and physician collaboration in the community and the Centers of Excellence,” he said. “The experts at Centers of Excellence have to work in partnership with the community doctors.”
Herr said setting up high-volume centers in every state would be another feasible approach to address the problem.
“The only real solution I can see is regional centers. Regional centers have to be set up where high-volume places — probably one, two or three in a state — are available, and patients will need to be transferred there,” he said.
Another crucial piece of the puzzle is to ensure that patients who are candidates for treatment with curative intent are fully aware of the consequences of refusing treatment. De Vere White said patients may be forgoing treatment due to issues of traveling distance or treatment-related adverse events without fully understanding the choice they are making.
“These patients need to be fully informed in making this decision. They need to understand the expected outcome of not getting treatment,” he told Healio. “The expected outcome is they will lose about 2 to 5 years of life and have a 75% chance of dying of bladder cancer. Also, based on the best data we have, there is a 40% to 50% chance they will be dead within a year.”
He added that the quality of life for that year typically is not good for these patients.
“The best we can say at this time is that there is no evidence that if you turn down those treatments based on side effects, your quality of life will be any better than if you had the treatment,” he said.
For more information:
Ralph de Vere White MD can be reached at 4501 X St. #3003, Sacramento, CA 95817; email: rwdeverewhite@ucdavis.edu.
Harry Herr, MD can be reached at 1275 York Ave., New York, NY 10065; email: herrh@mskcc.org.
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