OBJECTIVES:The urokinase plasminogen activation (uPA) system plays an important role in tumor invasion and metastasis by mediating proteolysis, adhesion, and migration of tumor cells. We tested the hypothesis that preoperative plasma levels of uPA and its specific receptor, uPAR, would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder.METHODS:The study group consisted of 51 patients who underwent radical cystectomy for muscle-invasive cancer or Tis, Ta, or T1 transitional cell carcinoma refractory to intravesical therapy and 44 men without cancer. Preoperative plasma levels of uPA and uPAR were measured by enzyme-linked immunosorbent assay in patients with available samples (51 and 38, respectively) and correlated with the clinical and pathologic characteristics and clinical outcome.RESULTS:Plasma uPA and uPAR levels were both greater in those with bladder cancer than in the healthy subjects (P <0.001). Plasma uPAR levels were greatest in patients with metastases to distant lymph nodes (P = 0.042). Preoperative uPA was independently associated with metastases to regional lymph nodes (P = 0.017), lymphovascular invasion (P = 0.019), disease progression (P = 0.030), and death from bladder cancer (P = 0.038). uPAR was not associated with bladder cancer outcome.CONCLUSIONS:Plasma uPA and uPAR levels were greater in those with bladder cancer compared with healthy controls. For patients with bladder cancer, a greater preoperative plasma uPA level was an independent predictor of poor outcome after radical cystectomy.

Purpose: Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta(1) (TGF-beta(1)).Patients and Methods: Between November 7,1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta(1), were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance.Results: In the multivariable Cox model, PSA (P = .004), IL6SR (P < .001), TGF-beta(1) (P < .001), primary Gleason grade (P < .002), and secondary Gleason grade (P = .029) were associated with PSA progression, whereas clinical stage (P = .696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta(1) achieved a concordance index of only 0.75.Conclusion: We found that pretreatment plasma levels of IL6SR and TGF-beta(1) improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated. (C) 2003 by American Society of Clinical Oncology.

PURPOSE:Elevated levels of interleukin-6 (IL-6) are associated with metastasis and poor prognosis in various malignancies. Since the IL-6 soluble receptor (IL-6sR) potentiates the systemic effects of IL-6, each may independently impact the disease process. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder.MATERIALS AND METHODS:The study group consisted of 51 patients who underwent radical cystectomy for transitional cell carcinoma and 44 men without cancer. Preoperative plasma levels of IL-6 and IL6sR were measured by enzyme-linked immunosorbent assay and correlated with pathological features and clinical outcome.RESULTS:IL-6 levels were higher in patients with bladder cancer than in healthy controls (p <0.001). In bladder cancer cases elevated levels of IL-6 and IL-6sR were associated with adverse pathological features, including muscle invasion, lymphovascular invasion and lymph node metastases (p <0.05). High levels of IL-6sR were also associated with pathological tumor grade (p = 0.036). In separate multivariate models that included clinical stage and grade IL-6 and IL-6sR levels were independent predictors of lymphovascular invasion, metastases to lymph nodes, disease recurrence and disease specific survival (p <0.05). In a preoperative Cox proportional hazards model IL-6 (p = 0.050) and IL-6sR (p = 0.035) predicted disease specific survival.CONCLUSIONS:We found that plasma IL-6 levels were higher in patients with bladder cancer than in healthy controls. Levels of IL-6 and IL-6sR were associated with cancer stage and metastases, and were strong independent predictors of disease recurrence and disease specific survival.

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 TI TCC (4.5 +/- 1.2 ng/mL) and healthy subjects (4.5 +/- 1.2 ng/mL; P < 0.001). Preoperative plasma TGF-P, 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. (C) 2001 American Cancer Society.

Objectives. Elevated circulating levels of interleukin 6 (IL-6) have been associated with cancer metastasis. IL-6 binds either to membrane or to soluble IL-6 receptor (IL-6sR), which then induces homodimerization of gp130 that activates downstream signaling. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels are associated with prostate cancer stage, progression, and metastasis after radical prostatectomy.Methods. Plasma levels of IL-6 and IL-6sR were measured in 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer, 44 healthy men without any cancer, 19 men with prostate cancer metastatic to the regional lymph nodes, and 10 men with prostate cancer metastatic to bone.Results. Plasma IL-6 and IL-6sR levels were highest in patients with bone metastases (P<0.001). The preoperative IL-6 and IL-6sR levels were associated with the preoperative prostate-specific antigen (PSA) level (P0.041), prostatectomy tumor volume (P less than or equal to0.048), and final Gleason sum (P less than or equal to0.042). The preoperative IL-6 and IL-6sR levels and biopsy Gleason sum were independent predictors of PSA progression (P less than or equal to0.029). However, in a model that included both IL-6 and IL-6sR, only IL-6sR and the biopsy Gleason sum predicted progression (P less than or equal to0.040). In patients whose disease progressed, the preoperative IL-6 and IL-6sR levels were highest in those with presumed aggressive failure (P less than or equal to0.042).Conclusions. Plasma IL-6 and IL-6sR levels were dramatically elevated in the men with prostate cancer metastatic to bone. In patients with clinically localized prostate cancer, the preoperative plasma IL-6 and IL-6sR levels independently predicted biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy. UROLOGY 58: 1008-1015, 2001. (C) 2001, Elsevier Science Inc.