Bladder cancer can take many forms, ranging from wart-like growths that are not life-threatening to a highly malignant, rapidly fatal disease. Currently, it is very difficult to determine the biologic potential of bladder cancer from its appearance, even under the microscope. For this reason, we are developing new indicators to predict the behavior of individual bladder cancers. Our research makes use of the rapidly developing field of genetic markers and very sensitive tests for genetic damage. This theme guides our approach to the entire spectrum of bladder cancer. The challenges of treating each stage appear below.
Early stage bladder cancer
Most patients discover that they have bladder cancer after seeking medical attention for blood in the urine. For most patients, the detectable cancer is confined to the bladder, and is therefore potentially curable. The challenge is to match each patient with the most appropriate therapy. When the cancer is entirely within the lining of the bladder (Stage Ta), and especially when it is not high-grade (highly cancerous), the usual treatment is removal of the cancer using instruments passed through the urinary channel. However, some patients with Ta cancers will progress to more threatening cancers. The early identification of these patients, while their disease is still curable, is an important area of clinical research.
Invasive bladder cancer
For patients with high-grade cancers or cancers that have started to invade into the bladder wall (stage T1), the usual therapy (called BCG) has been shown to be highly effective in the short term, with about 85% of patients showing marked improvement. However, most patients will eventually have recurrent cancer despite BCG. At present, there is no standard therapy for patients that do not benefit from BCG. Being able to predict who will be adequately treated with BCG, and developing therapies for those who fail BCG treatment is a very active area of research. We have made a major, long-term commitment to study gene therapy and other novel forms of treatment. We have recently completed a trial of p53 gene therapy, and will be studying a form of the retinoblastoma gene (RB94) very soon.
For patients with invasion into the muscular wall of the bladder (stage T2), the standard treatment remains cystectomy or partial cystectomy (removal of all or part of the bladder). We are working on refining the criteria for how to select the extent of surgery, and also how to monitor the portion of the bladder that is left behind. Unfortunately, up to 40 to 50% of patients with cancers that seem to be confined to the bladder wall will have life-threatening, recurrent cancer despite prompt surgical removal of the bladder. Currently, we are trying to identify the patients at risk of recurring so that additional therapy can be offered.
Locally advanced bladder cancer
When the cancer is outside the bladder (i.e., stage T3 or T4), surgical cure rates are only in the range of 10 to 30%. By use of both surgery and chemotherapy, the expectation of cure increases to about 60%. Currently, we give the chemotherapy first, since this allows us to assess the response in each patient. Metastatic bladder cancer patients have been an important group for us to study, because we can directly relate characteristics of their cancer to sensitivity to chemotherapy, and the overall probability of cure.
Metastatic bladder cancer
Patients with bladder cancer that has spread to distant sites, i.e., metastatic bladder cancer, are treated with chemotherapy. We have been very active in developing new combinations of chemotherapy drugs, and developing new ways of studying these combinations in clinical trials. Among other things, we are studying the interaction of gemcitabine with other drugs that damage DNA. We are also developing brand-new chemotherapy drugs and treatments for patients that are not healthy enough to withstand traditional therapy. Our goal is to find new therapeutic solutions, since it is clear that traditional chemotherapy alone does not provide long-term control of the disease in most patients.
For more information about recent findings in bladder cancer research at MD Anderson, see our list of recent publications.