Prediction of response to treatment in superficial bladder carcinoma through pattern of interleukin-2 gene expression

Purpose: Superficial bladder carcinoma, treated by resection and intravesical administration of bacillus Calmette-Guerin (BCG), yields a remission rate that approaches 70%, We examined whether expression of interleukin-2 (IL-2) or interferon-gamma (IFN-gamma) genes can serve to predict response. Patients and Methods: During BCG treatment, we analyzed induction of IL-2 and IFN-gamma mRNA in peripheral-blood mononuclear cells (PBMC) from 73 patients: 51 with papillary tumors and 22 with carcinoma-in-situ (CIS). Results were correlated with remission, relapse, or tumor persistence over a 4-year follow-up period. Results: Independent of tumor type, induction of IL-2 mRNA was observed for patients who responded with remission, but not far those who relapsed (P = .0001). Multivariate logistic analysis showed that inducibility of IL-2 mRNA is the discriminating parameter, which yields a predictive value of 97% for remission, Of 23 patients with relapse/persistence, 22 lacked inducibility of IL-2 mRNA (sensitivity, 95.6%), while 35 of 50 patients ire remission exhibited inducibility (specificity, 70%), For patients with carcinoma-in-situ, in which remission or failure depends solely on response to BCG, sensitivity and specificity were 88% and 86%, respectively; for patients with papillary tumors, they were 100% and 64%. IFN-gamma mRNA, by contrast, was clearly inducible in PBMC from all patients (P = .51), The disease-free interval increased progressively with inducibility of IL-2 mRNA; this trend was highly significant (P = .0001). Conclusion: IL-2 gene expression is essential for mounting an antitumor response in superficial bladder carcinoma, Inducibility of IL-2 mRNA is an independent prognostic parameter and useful predictive indicator of remission versus relapse. (C) 1996 by American Society of Clinical Oncology.