The Addition of Interleukin-6 Soluble Receptor and Transforming Growth Factor Beta<sub>1</sub> Improves a Preoperative Nomogram for Predicting Biochemical Progression in Patients With Clinically Localized Prostate Cancer

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

doi:10.1200/jco.2003.12.037

Cited by 197 publications

(110 citation statements)

References 24 publications

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“…This approach has been previously reported by other authors for the prediction of a positive biopsy outcome 32 or the risk of biochemical failure subsequent to radical prostatectomy. 33 …”

Section: Discussionmentioning

confidence: 99%

Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy

Steuber

Vickers

Haese

et al. 2007

Intl Journal of Cancer

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Clinicians currently use simple cut-points, such as serum prostatespecific antigen (PSA) 4 ng/ml, to decide whether to recommend further work-up for prostate cancer (PCa). As an alternative strategy, we evaluated multivariable models giving probabilities of a PCa diagnosis based on PSA and several circulating novel biomarkers. We measured total PSA, free PSA (fPSA), fPSA subfractions (single-chain fPSA-I and multichain fPSA-N), total human glandular kallikrein 2 (hK2) and full-length and cleaved forms of soluble urokinase plasminogen activator receptor (suPAR) in pretreatment serum from 355 men referred for prostate biopsy. Age and total PSA were combined in a ''base'' regression model to predict biopsy outcome. We then compared this base model to models supplemented by various combinations of circulating markers, using concordance index (AUC) to measure diagnostic discrimination. PCa prediction was significantly enhanced by models supplemented by measurements of suPAR fragments and fPSA isoforms. Addition of these markers improved bootstrap-corrected AUC from 0.611 for a cut-point and 0.706 for the base model to 0.754 for the full model (p 5 0.005). This improved diagnostic accuracy was also seen in subanalysis of patients with PSA 2-9.99 ng/ml and normal findings on DRE (0.652 vs. 0.715, p 5 0.039). In this setting, hK2 did not add diagnostic information. Measurements of individual forms of suPAR and PSA isoforms contributed significantly to discrimination of men with PCa from those with no evidence of malignancy. ' 2006 Wiley-Liss, Inc.

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“…This approach has been previously reported by other authors for the prediction of a positive biopsy outcome 32 or the risk of biochemical failure subsequent to radical prostatectomy. 33 …”

Section: Discussionmentioning

confidence: 99%

Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy

Steuber

Vickers

Haese

et al. 2007

Intl Journal of Cancer

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“…When Kattan et al added interleukin-6 soluble receptor and TGFb to their nomogram, clinical stage lost its significance in predicting recurrence (27) in multivariate analysis. Recently, Yegnasubramanian et al showed in a subgroup of their study population analysis that CpG island hypermethylation of PTGS2 predicted for increased risk of recurrence following a radical prostatectomy, whereas pathologic stage lost its significance as well (28).…”

Section: Discussionmentioning

confidence: 99%

Promoter Hypermethylation as an Independent Prognostic Factor for Relapse in Patients with Prostate Cancer Following Radical Prostatectomy

Rosenbaum

Hoque²,

Cohen³

et al. 2005

Clinical Cancer Research

123

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Purpose: To analyze the prognostic significance of six epigenetic biomarkers (APC, Cyclin D2, GSTP1, TIG1, Rassf1A , and RARb2 promoter hypermethylation) in a homogeneous group of prostate cancer patients, following radical prostatectomy alone. Patients and Methods: Biomarker analyses were done retrospectively on tumors from 74 prostate cancer patients all with a Gleason score of 3 + 4 = 7 and minimum follow-up period of 7 years. Using quantitative methylation-specific PCR, we analyzed six gene promoters in primary prostate tumor tissues. Time to any progression was the primary end point, and development of metastatic disease and/or death from prostate cancer was a secondary point.The association of clinicopathologic and biomolecular risk factors to recurrence was done using the log-rank test and Cox proportional hazards model for multivariate analysis. To identify independent prognostic factors, a stepwise selection method was used. Results: At a median follow-up time of 9 years, 37 patients (50%) had evidence of recurrence: biochemical/prostate-specific antigen relapse, metastases, or death from prostate cancer. In the final multivariate analysis for time to progression (TTP), the significant factors were age > 60[hazard ratio (HR), 0.4; 95% confidence interval (95% CI), 0.2-0.8; P = 0.01], hypermethylation of GSTP1 (HR, 0.23; 95% CI; 0.09-0.64; P = 0.004), and hypermethylation of APC (HR, 3.0; 95% CI, 1.42-6.32; P = 0.004). In another multivariate analysis, a profile of hypermethylation of APC and cyclin D2 hypermethylation was significant as well: if either any one was hypermethylated (HR, 1.84; 95% CI, 0.92-3.72; P = 0.09) or if both were hypermethylated (HR, 4.3; 95% CI, 1.52-12.33; P = 0.01). Conclusions: Methylation status of selected genes in the prostate cancer specimen may predict for time to recurrence in Gleason 3 + 4 = 7 patients undergoing prostatectomy. These results should be validated in a larger and unselected cohort.

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“…24 In contrast, platelet-free plasma levels of transforming growth factor b 1 (TGF-b 1 ) and interleukin-6 soluble receptor, which have been reported to be markedly elevated in patients with distant metastases from PCa, significantly enhanced prediction of BCR over the standard Kattan pretreatment nomogram (concordance index of 0.75 vs. 0.83 for a model supplemented by TGF-b 1 and interleukin-6 receptor). 25 Measurements of prostate-specific tissue kallikreins such as multiple PSA-forms and hK2 in blood have been shown to improve early detection and staging of PCa. 11,12,26 However, there are no previous data reported whether these measurements may enhance the predictive accuracy of the standard pretreatment model to assess risk for BCR.…”

Section: Discussionmentioning

confidence: 99%

Risk assessment for biochemical recurrence prior to radical prostatectomy: Significant enhancement contributed by human glandular kallikrein 2 (hK2) and free prostate specific antigen (PSA) in men with moderate PSA‐elevation in serum

Steuber

Vickers

Haese

et al. 2005

Intl Journal of Cancer

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Most models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate‐specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate‐specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this “base” model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA ≤ 14 ng/ml (13%), and 28 patients (10%) with a pretreatment tPSA ≤ 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap‐corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA‐elevation (tPSA ≤ 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756–0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for “moderately elevated” PSA. For patients with a moderate tPSA‐elevation (tPSA ≤ 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR‐prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR. © 2005 Wiley‐Liss, Inc.

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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

Cited by 197 publications

References 24 publications

Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy

Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy

Promoter Hypermethylation as an Independent Prognostic Factor for Relapse in Patients with Prostate Cancer Following Radical Prostatectomy

Risk assessment for biochemical recurrence prior to radical prostatectomy: Significant enhancement contributed by human glandular kallikrein 2 (hK2) and free prostate specific antigen (PSA) in men with moderate PSA‐elevation in serum

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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

Cited by 197 publications

References 24 publications

Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy

Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy

Promoter Hypermethylation as an Independent Prognostic Factor for Relapse in Patients with Prostate Cancer Following Radical Prostatectomy

Risk assessment for biochemical recurrence prior to radical prostatectomy: Significant enhancement contributed by human glandular kallikrein 2 (hK2) and free prostate specific antigen (PSA) in men with moderate PSA‐elevation in serum

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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