Preoperative Plasma Levels of Transforming Growth Factor Beta(1) Strongly Predict Clinical Outcome in Patients with Bladder Carcinoma

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.