UroToday - In the May issue of the Journal of Urology, Joudi and colleagues from Iowa City report data from a national phase II multicenter trial of intravesical BCG plus interferon-alpha. The cohort consisted of 1,106 patients treated with 81 mg of BCG plus 50 MU IFN-alpha if BCG naďve, one-third of the BCG dose with 50 MU IFN-alpha if previously treated with BCG, or one-tenth the BCG dose with 100 MU IFN-alpha if previously intolerant to BCG. The inclusion criteria consisted of patients with all types of superficial bladder cancer, with or without CIS, and with or without prior intravesical chemotherapy or immunotherapy.
After a follow-up of 24 months, overall cancer-free rates were 45% for patients younger than 50 years, 59% for ages 51-60, 61% for 61-70 years, 49% for 71-80 years, and 39% for patients older than 80 years. Patients older than 80 years had a 74% higher likelihood of not responding to intravesical BCG plus IFN-alpha (Hazard ratio: 1.74, 95% CI 1.377 - 2.73). In multivariate analysis, age was an independent predictor of poor outcome after controlling for stage, grade, tumor size, sex, prior therapy, and maintenance therapy. Interestingly, patients younger than 50 years also exhibited a worse outcome (HR 1.54, 95% CI 1.07 - 2.37). Nevertheless, young patients who were previous BCG failures responded well to BCG plus IFN-alpha, suggesting that these patients have a preserved immune recall.
These data suggest that in a mixed cohort of patients with superficial bladder cancer treated with varying doses of intravesical BCG plus IFN-alpha, advanced age was associated with a decreased response even to salvage immunotherapy. The author's postulate that the depressed immune status of the elderly may account for a decreased immunological response preventing the synthesis of essential cytokines (such as IL-2) required for BCG efficacy. As suggested by Dr. Lamm in the accompanying editorial, perhaps combination intravesical therapy with BCG and interleukin-2 should receive more intense study in this cohort of patients.
By Ricardo F. Sánchez-Ortiz, MD
Reference:
J Urol. 2006 May; 175(5):1634-40.
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Joudi FN, Smith BJ, O'Donnell MA, Konety BR
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