Does age have an effect on response of superficial bladder cancer to intravesical immunotherapy ?

Data from 1008 patients with superficial bladder cancer enrolled in a phase II study of combination BCG (Bacillus Calmette-Guerin) plus Interferon-alpha were analyzed. Response rates were obtained by age decade. Patients 61-70 years of age had the best response rate with 61% cancer free survival at a median follow up of 24 months. Patients > 80 years old had an overall poor response rate ( 39%). Response rates were even lower in this group of  patients if they had previously been treated with BCG ( 47% for BCG naive patients versus 32% for BCG failure patients). Multivariate analysis showed that age was a significant independent prognostic factor ( p=0.024). Patients > 80 years old had a 74% higher likelihood of not responding to BCG plus Interferon-alpha compared to patients 61-70 years old. Patients < 50 years of age also had a poor response rate of 45%.

Enhanced urinary T-helper type 1 cytokine levels (IL-2 and IFN-γ) have been observed during intravesical BCG therapy and they may be associated with an immune reaction that is necessary to eradicate bladder cancer. It is  known that  response to intravesical immunotherapy relies on a robust immune system that generates a vigorous immune response. Bladder cancer is a disease of older patients with analysis of SEER (Surveillance, Epidemiology, and End Results) database showing that 64% of the patients were age 65 or older. This may become a more significant health issue as life expectancy improves. The effect of a waning immune system has been seen in other tumors like melanoma and renal cell carcinoma. Based on our findings we  hypothesize that older patients had a poor response due to their depressed baseline immune status and subsequent inability to launch an adequate immune response.   One can suggest that older patients can be evaluated for an immune response by checking urine cytokines ( like IL-2 ). The implication of this would be that alternative therapy ( intravesical chemotherapy vs cystectomy) could be considered in patients who cannot launch an immune response . Further studies evaluating the influence of age on the response in other databases are warranted.

Bibliographical refrence:

Joudi FN et al.: "The impact of age on the response of patients with superficial bladder cancer to intravesical immunotherapy", J Urol. 2006 May;175(5):1634-9

Fadi N. Joudi

Department of Urology, University of Iowa, Iowa City, Iowa, USA