Preoperative plasma levels of transforming growth factor beta(1) strongly predict clinical outcome in patients with bladder carcinoma.

Abstract

Elevated local and circulating levels of transforming growth factor (TGF)-beta(1) have been associated with cancer invasion, progression, and metastasis. The authors tested the hypothesis that preoperative plasma TGF-beta(1) levels would independently predict cancer stage and prognosis in patients with transitional cell carcinoma (TCC) of the urinary bladder. The study group consisted of 51 patients who underwent radical cystectomy for muscle-invasive or intravesical immuno- and/or chemotherapy refractory Tis, Ta, or T1 TCC (median follow-up, 45.7 months). Preoperative plasma levels of TGF-beta(1) were measured and correlated with pathologic features and clinical outcome. Transforming growth factor-beta(1) levels also were measured in 44 healthy men without any cancer. The mean preoperative plasma TGF-beta(1) level in patients who eventually developed metastases to distant (11.9 +/- 0.9 ng/mL) or regional (9.6 +/- 2.4 ng/mL) lymph nodes was significantly higher than that in patients with nonmetastatic muscle-invasive TCC (5.4 +/- 1.1 ng/mL), which, in turn, was significantly higher than that in patients with nonmetastatic Tis, Ta, or T1 TCC (4.5 +/- 1.2 ng/mL) and healthy subjects (4.5 +/- 1.2 ng/mL; P < 0.001). Preoperative plasma TGF-beta(1) level was an independent predictor of lymphovascular invasion (P = 0.002), metastases to lymph nodes (P = 0.030), disease recurrence (P = 0.009), and disease specific survival (P = 0.015). In a subgroup of patients with muscle-invasive TCC, TGF-beta(1) level was associated with disease recurrence (P = 0.005) and death from bladder carcinoma (P = 0.001). The authors confirm that plasma TGF-beta(1) levels are elevated in patients with muscle-invasive TCC before cystectomy. Transforming growth factor-beta(1) levels are highest in patients with bladder carcinoma metastatic to lymph nodes and are a strong independent predictor of disease recurrence and disease specific mortality.