Correlation of preoperative levels of IGF-I and IGFBP-3 with pathologic parameters and clinical outcome in patients with bladder cancer.

OBJECTIVES

To test the hypothesis that plasma insulin growth factor (IGF)-I or IGF binding protein (BP)-3 levels would differ between patients with bladder cancer and healthy controls and whether preoperative plasma IGF-I or IGFBP-3 could predict the pathologic characteristics and clinical outcome of patients with bladder cancer undergoing radical cystectomy. The IGFs are mitogens that have been shown to play a significant role in regulating proliferation and differentiation of bladder cancer cells.

METHODS

The study group consisted of 51 patients who underwent radical cystectomy (median follow-up 45.7 months). The preoperative plasma levels of IGF-I and IGFBP-3 were measured using DSL-enzyme-linked immunosorbent assays. The IGF-I and IGFBP-3 levels were also measured in 44 healthy men.

RESULTS

The plasma IGF-I and IGFBP-3 levels in patients with bladder cancer were not significantly different from those in healthy subjects (P >or=0.339). In a preoperative model that included clinical grade, clinical stage, and either IGF-I or IGFBP-3, none of the parameters was associated with either metastases to lymph nodes or clinical outcome. However, in an alternative model that included both IGF-I and IGFBP-3 in addition to clinical stage and grade, only a lower preoperative plasma IGFBP-3 level was associated with metastases to regional lymph nodes, bladder cancer progression, and survival (P = 0.047, 0.050, and 0.040, respectively).

CONCLUSIONS

We found no association between preoperative plasma IGF-I and bladder cancer characteristics or outcome, limiting the clinical utility of IGF-I. In contrast, a lower preoperative plasma level of IGFBP-3 was associated with lymph node metastasis and poorer clinical outcome after radical cystectomy when adjusted for IGF-I level.