Urinary fibronectin levels: Aiming for establishing the best timing of BCG intravesical instillation after TUR-BT

Introduction and Objectives: Intravesical BCG treatment in superficial transitional cell carcinoma (TCC) patients is well established. It has been found that the first step in BCG activity is attachment to bladder wall through high affinity receptors to Fibronectin. Fibronectin, a matrix glycoprotein in basement membranes, exists also in soluble form in plasma and other body fluids. BCG was found to bind to matrix Fibronectin at the exposed areas following TURBT. On the other hand, BCG binding and subsequently its antitumor activity, were inhibited by administration of exogenous soluble Fibronectin into the bladder, through a competitive receptor binding mechanism. Thus, urinary Fibronectin, originating from- bleeding points or from tumor destruction, could interfere with Fibronectin-BCG binding and could significantly lower BCG efficacy if BCG was administered too early. We conducted this trial as to fully characterize urinary Fibronectin levels following TUR-BT. Our results should help in establishing a scientific basis of the correct timing for BCG intravesical instillation. Methods: Morning urine samples were collected in 25 patients admitted for TUR-BT for bladder TCC. Urine specimens were collected before and another 7 samples on days 2-28 after TUR-BT. We documented the following data: tumor volume, area and depth of resection, macroscopic hematuria in samples and pathological stage and grade. Fibronectin urine level was measured by ELISA Results: In 21 patients significant increase in Fibronectin level was measured after operation. In 10 patients with elevated pre-op levels, a 100-fold increase was noticed. Urinary Fibronectin levels decreased to minimal values or disappeared within 15 days in 18 patients. Hématuric samples showed significantly higher levels. No correlation was found between the other mentioned parameters and Fibronectin peak level or decline rate. Conclusions: Urinary Fibronectin level is undetectable in most patients 2 weeks after operation and should not interfere with BCG attachment. Instillation of BCG less than 2 weeks after TUR-BT may be much less effective and is not recommended. Macroscopic hematuria may lower BCG binding and waiting to its cessation should be considered.