Certain bladder-cancer patients may be at high risk of disease recurrence despite bladder removal
Patients with advanced bladder cancers that are surgically removed might need additional therapy to prevent recurrence in certain situations, a new UT Southwestern Medical Center study suggests.
The five-year international study led by researchers at UT Southwestern validates the use of a marker panel to predict which patients are more likely to have a recurrence of cancer after bladder removal, thereby identifying those patients as good candidates for follow-up chemotherapy.
The findings, published in the most recent edition of European Urology, are important because additional molecular information could help bladder-cancer patients and their physicians decide whether administering further toxic chemotherapy is worth the risk, said Dr. Yair Lotan, professor of urology at UT Southwestern and the study’s primary investigator and first author.
Bladder cancer is the fourth most common cancer diagnosed in men, according to the American Cancer Society. The ACS estimates that more than 72,500 cases will be diagnosed in the United States this year, and that more than 15,200 people will die from the disease in 2013.
Patients with muscle-invasive bladder cancer typically are treated by removing all or part of the bladder (a cystectomy procedure) but are infrequently given additional chemotherapy, despite an overall relapse rate of one in every three cases.
Using five commercially available markers and the tissues of patients who had their bladders removed, UT Southwestern researchers in the departments of urology and pathology and the Harold C. Simmons Cancer Center monitored a group of 216 patients to track if their cancers recurred.
What is bladder cancer and how common is it?
Bladder cancer is a common cancer. About 10,000 people develop bladder cancer in the UK each year. In most cases in the UK, the bladder cancer develops from the transitional cells which line the inside of the bladder. This type of cancer is called transitional cell bladder cancer. Other types of bladder cancer are rare in the UK.
The rest of this leaflet only deals with the common type of bladder cancer - transitional cell bladder cancer.
Transitional cell bladder cancer is divided into two groups:
Superficial tumours. These occur in about 4 in 5 cases. These tumours are confined to the inner lining, or just below the inside lining, of the bladder. Sometimes the cells which form this type of cancer multiply to form little growths which stick out like warts from the inside lining of the bladder.
Muscle invasive tumours. These occur in about 1 in 5 cases. These tumours have spread to the muscle layer of the bladder, or right through the wall of the bladder.
The treatment and outlook for each of these two groups are very different. Superficial tumours rarely spread and can usually be cured. However, if left untreated, in some cases they can develop into muscle invasive tumours. Muscle invasive tumours have a high chance of spreading to other parts of the body (metastasise), and treatment has less chance of being curative.
When controlled for pathologic factors such as stage, grade, lymphovascular invasion, lymph node status, surgical margin status, and whether the patients had already received chemotherapy, the number of altered biomarkers were found to be an independent predictor of recurrence and cancer-specific mortality, the researchers found.
“It is well known that bladder cancer tumors have certain molecular alterations, but the problem is that there has been little data regarding which patients should get additional therapy, especially if there is no radiologic or pathologic evidence that the cancer has spread beyond the bladder,” Dr. Lotan said. “This situation exists despite the fact that approximately 35 percent of patients treated by cystectomy develop metastatic disease and many of these individuals die of their disease.”
Bladder cancer patients over 70 less likely to get curative treatment
Older bladder cancer patients are less likely than younger patients to receive treatments intended to cure their disease such as surgery to remove the bladder or radiotherapy. But this difference cannot be fully explained by age, according to new research by scientists published in the British Journal of Cancer1.
Researchers, funded by Yorkshire Cancer Research at the University of Sheffield, looked at the records of around 3,300 bladder cancer patients diagnosed in Sheffield between 1994 and 2009. They wanted to investigate how age, type of bladder cancer and treatment affected the chances of surviving the disease2.
They found that 52 per cent of patients under 60 had potentially curative treatments such as surgery or radiotherapy, compared with 34 per cent of patients in their 70s and only 12 per cent of patients over 80.
And older patients over 70 were more likely to die of their bladder cancer than younger patients.
The researchers believe that the higher number of deaths in those over 70 is because these patients had a higher proportion of more aggressive tumours and were less likely to receive radical treatments such as radiotherapy or surgery to remove the bladder and nearby organs.
The investigation’s goal was to establish whether molecular markers that are involved in cell cycle regulation and proliferation could help identify those patients at higher risk for recurrence or metastasis following bladder-cancer surgery, Dr. Lotan said.
The next steps will be to try to incorporate the molecular marker panel into clinical practice. Dr. Lotan is also a member of the Simmons Cancer Center.
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Other UT Southwestern researchers involved in the study are Dr. Arthur Sagalowsky, professor of urology and surgery; Dr. Ganesh Raj, associate professor of urology; Dr. Payal Kapur, associate professor of pathology; Dr. Vitaly Margulis, assistant professor of urology; Dr. Yull Arriaga, assistant professor of internal medicine; Dr. Aditya Bagrodia, urology resident; and medical student Varun Rachakonda. Medical oncologists and urologists from NewYork-Presbyterian/Weill Cornell Medical Center; the University Vita-Salute San Raffaele in Milan, Italy; and the University of Heidelberg’s Mannheim Medical Center in Germany also contributed to the research.
Please visit the Harold C. Simmons Cancer Center to learn more about clinical services for oncology at UT Southwestern, including highly individualized treatments for cancer at the region’s only National Cancer Institute-designated center.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 100,000 hospitalized patients and oversee more than 2.1 million outpatient visits a year.
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