Originally published as JCO Early Release 10.1200/JCO.2003.12.037 on August 11 2003

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The Addition of Interleukin-6 Soluble Receptor and Transforming Growth Factor Beta₁ Improves a Preoperative Nomogram for Predicting Biochemical Progression in Patients With Clinically Localized Prostate Cancer

Michael W. Kattan, Shahrokh F. Shariat, Ben Andrews, Kuichun Zhu, Eduardo Canto, Kazumasa Matsumoto, Masatoshi Muramoto, Peter T. Scardino, Makoto Ohori, Thomas M. Wheeler, Kevin M. Slawin

From the Baylor Prostate Center, the Scott Department of Urology, and Department of Pathology, Baylor College of Medicine; the Methodist Hospital, Houston, TX; and the Departments of Urology and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Kevin M. Slawin, MD, Scott Department of Urology, Baylor College of Medicine, 6535 Fannin St, Houston, TX 77030; e-mail: kslawin{at}bcm.tmc.edu.

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 beta₁ (TGF-ß₁).

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-ß₁ 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-ß₁ (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-ß₁ achieved a concordance index of only 0.75.

Conclusion: We found that pretreatment plasma levels of IL6SR and TGF-ß₁ 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.

Supported in part by grants from the Austrian Science Fund, the Frost Foundation, Inc, and the National Cancer Institute Specialized Program of Research Excellence (SPORE CA58203).

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