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.
OBJECTIVE
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-beta1).


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-beta1 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-beta1 (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-beta1 achieved a concordance index of only 0.75.


CONCLUSIONS
We found that pretreatment plasma levels of IL6SR and TGF-beta1 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.
Kattan
Michael W
MW
Scott Department of Urology, Baylor College of Medicine, 6535 Fannin St, Houston, TX 77030, USA. kslawin@bcm.tmc.edu.
Shariat
Shahrokh F
SF
Andrews
Ben
B
Zhu
Kuichun
K
Canto
Eduardo
E
Matsumoto
Kazumasa
K
Muramoto
Masatoshi
M
Scardino
Peter T
PT
Ohori
Makoto
M
Wheeler
Thomas M
TM
Slawin
Kevin M
KM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery; D019947:Receptors, Interleukin-6 / Q000032:analysis*; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1
D014408:Biomarkers, Tumor; D019947:Receptors, Interleukin-6; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017430:Prostate-Specific Antigen