Evolving Paradigms In Bladder Cancer: Current Treatment Strategies

¹³Bladder cancer is treated by surgery, chemotherapy, immunotherapy, radiation therapy, or a combination of these modalities.

Surgery is employed in nearly every bladder cancer treatment strategy. Transurethral resection of bladder tumor (TURBT) is used to treat early bladder cancer. It is performed using a cystoscope inserted through the urethra. A wire loop on the end of the cystoscope is used to remove the cancer or burn it away using an electric current, a process called fulguration. Cystectomy is another procedure in which part of or the entire bladder is removed. Partial (segmental) cystectomy is performed in patients with low-grade tumors localized to one area of the bladder. In addition to the tumor itself, nearby lymph nodes are removed. Following this surgery, patients are able to urinate normally, but possibly will do so more often.

Radical cystectomy, in which the entire bladder is removed, is employed in patients with muscle-invasive disease. In addition to the bladder, any nearby lymph nodes and organs in which cancer has been detected are removed. The prostate is usually removed in men, and the uterus is sometimes removed in women.³⁰During radical cystectomy, the surgeon provides a new way for urine to leave the body. A bag may be carried outside of the patient’s body to collect urine, or part of the small intestine may be used to create a pouch inside of the patient’s body (ileal conduit).³¹

Chemotherapy is a treatment that is designed to kill cancer cells or prevent them from dividing. Chemotherapeutic agents may be delivered locally or systemically. For example, lower stages of bladder cancer may be treated with intravesical chemotherapy, in which chemotherapeutic agents are delivered directly into the bladder via catheter. Agents that are frequently used to treat bladder cancer intravesically are mitomycin and thiotepa; others include valrubicin, doxorubicin, and gemcitabine.

Alternatively, bladder cancers that have progressed outside of the bladder into nearby organs or distant metastatic sites may be treated with systemic chemotherapy in the attempt to kill both the local tumor, as well as tumor cells that have spread to other sites. Chemotherapy may be delivered as single agents or as a combination of agents.³⁰

Immunotherapy is a strategy for cancer treatment in which the patient’s immune system is stimulated to target cancer cells. Natural or synthetic agents are delivered to enhance, redirect, or restore the immune system’s ability to eradicate aberrant tumor cells. One immunotherapy that is utilized for early-stage bladder cancers is Bacillus Calmette-Guerin (BCG), a live, attenuated strain of Mycobacterium bovis. BCG is delivered intravesically directly into the bladder, activating local immune cells and killing tumor cells. Interferon is another intravesical, immunotherapeutic agent that is commonly used in treating bladder cancer. Interferons stimulate the immune system and program immune cells to kill cancer cells. The most common interferon applied to bladder cancer therapy is interferon alpha.³²

Radiation therapy is used to kill cancer cells by exposure to highenergy x-rays or other forms of radiation. There are two types of radiation therapy: external and internal. External radiation therapy directs radiation from a source outside of the body to a localized area of the body. Internal radiation uses a radioactive agent that is sealed within needles, catheters, seeds, or wires that are placed in proximity to or into the cancer.³³

FIGURE 6

Bladder cancer treatment is based primarily on tumor stage.describes treatments that are recommended for patients with nonmuscle-invasive disease (CIS and T1), muscle-invasive disease (T2, T3, and T4), and metastatic disease (T4).

TABLE 2

For carcinoma in situ and stage T1 bladder cancers, TURBT is performed with fulguration and is followed by intravesical chemotherapy or intravesical BCG immunotherapy. Alternatively, partial or radical cystectomy may be performed, or the patient may choose to enroll in a clinical trial.^13,34Seefor examples of clinical trials that are currently recruiting participants. In highly selected cases with T1 bladder cancer with limited lamina propria invasion and no CIS, observation only may also be suitable.13

Patients with stage T2, T3, or T4 bladder cancers may be treated in a number of ways. Because the disease is muscle-invasive, more radical approaches are usually employed to combat the cancer. For stage T2 tumors, partial or radical cystectomy is performed and is usually accompanied by neoadjuvant chemotherapy. Maximal TURBT with concurrent chemotherapy and radiation is another treatment option for patients with T2 bladder cancer. Patients with poor performance or extensive comorbid disease may choose TURBT alone or chemotherapy plus radiation. Finally, patients may enroll in clinical trials of experimental therapies.^13,34

Treatment of stage T3 and nonmetastatic T4 bladder cancer is usually radical cystectomy with or without neoadjuvant chemotherapy. Similar to patients with T2 bladder cancer, maximal TURBT with concurrent chemotherapy and radiation may be used to treat patients with T3 or nonmetastatic T4 bladder cancer. TURBT alone, chemotherapy alone, or chemotherapy plus radiation, or clinical trial participation are also available options.^13,34

Metastatic T4 bladder cancer is treated primarily with chemotherapy. Palliative therapy, including urinary diversion, external beam radiation therapy, and/or cystectomy, is another option to alleviate symptoms and improve quality of life. Clinical trials of new cancer drugs or strategies are available for all patients with stage T4 bladder cancer.^13,34