Advances in Bladder Cancer

Meta-analyses now confirm that immunotherapy with BCG provides superior protection from tumor recurrence when compared with chemotherapy. The value of maintenance BCG therapy is also confirmed by meta-analysis, and is magnified by the finding that BCG significantly reduces disease progression but, apparently, only when maintenance schedules are utilized. While significant controlled comparison of BCG maintenance schedules has not been accomplished, the advantage of maintenance therapy appears to be highest using the SWOG 3 week schedule: once a week for 3 weeks at 3, 6, 12, 18, 24, 30, and 36 months. However, only 16% of patients received treatment at each interval, so we anticipate that less frequent maintenance may be required. Side effects of BCG can be reduced by BCG cutting the dose to 1/3, 1/10, 1/30, and 1/100th as needed.

Immunotherapy with KLH or interferon appears to be less toxic. Patients treated conservatively remain at risk of recurrence in the prostatic urethra and upper tracts and must be followed closely. About 60% of high risk patients who continue to recur despite BCG can be rescued with BCG plus interferon. New agents such as BCG genetically engineered to produce human IL-2 or other cytokines are being developed, and agents such as Advexin, Velcade, Regressin may prove to be beneficial.

Patients who progress on conservative treatment tend to have higher stage disease and mortality than patients who present with invasive disease. Improved monitoring is greatly needed. Urinary FISH and CT or MRI urograms may detect unsuspected residual, invasive or extravesical disease and improve the safety of conservative therapy.

Cystectomy remains the gold standard for the treatment of muscle invasive disease, and the value of wide resection and extended pelvic lymphadenectomy is increasingly appreciated. Advances in cystoprostatectomy including orthotopic neobladder, now accepted and successful in women as well as men, nerve-sparing cystoprostatectomy, and sural or genitofemoral nerve grafts have improved patient quality of life. In advanced disease MVAC remains the standard, and has been further improved with high density MVAC. Comparable results with less side effects appear to be obtained with newer agents such as gemcitabine and paclitaxel combined with cisplatin. New drugs such as pemetrexate (Alimta) and capecitabine (Xeloda) as well as angiogenesis, growth factor inhibitors, and proteosome inhibitors need to be evaluated to improve survival in patients who fail MVAC.

Created: 3/15/2005