Beyond prostate-specific antigen: new serologic biomarkers for improved diagnosis and management of prostate cancer.

The use of total prostate-specific antigen (tPSA) measurement has dramatically improved the ability to detect prostate cancer at earlier stages. However, as the number of men presenting with advanced disease (and high tPSA levels) has decreased, and given the fact that tPSA is highly reflective of benign prostatic hyperplasia, the need has emerged for novel biomarkers specifically associated with prostate cancer in order to improve predictive models. Several new biomarkers have shown promise, and studies continue to investigate the role of these markers in the detection, staging, and prognosis of prostate cancer. As new useful biomarkers continue to emerge, guidelines for their employment, as well as coordination of further research studies, are needed; a systematic, phased, nomogram-based model is a rational way to manage these efforts.

[1]  R. Kane,et al.  Prostate‐specific antigen lewels in 1695 men without evidence of prostate cancer: Findings of the American cancer society national prostate cancer detection project , 2010, Cancer.

[2]  T. Wheeler,et al.  Effects of systematic 12-core biopsy on the performance of percent free prostate specific antigen for prostate cancer detection. , 2004, The Journal of urology.

[3]  T. Wheeler,et al.  Tissue expression of transforming growth factor-beta1 and its receptors: correlation with pathologic features and biochemical progression in patients undergoing radical prostatectomy. , 2004, Urology.

[4]  M. Kattan,et al.  Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression , 2004, Clinical Cancer Research.

[5]  Michael W Kattan,et al.  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. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  M. Kattan,et al.  Preoperative blood reverse transcriptase-PCR assays for prostate-specific antigen and human glandular kallikrein for prediction of prostate cancer progression after radical prostatectomy. , 2002, Cancer research.

[7]  Pierre I Karakiewicz,et al.  International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  A. Partin,et al.  Free prostate-specific antigen in serum is becoming more complex. , 2002, Urology.

[9]  M. Kattan,et al.  Percent free prostate specific antigen is not an independent predictor of organ confinement or prostate specific antigen recurrence in unscreened patients with localized prostate cancer treated with radical prostatectomy. , 2002, The Journal of urology.

[10]  M. Kattan,et al.  Association of preoperative plasma levels of insulin-like growth factor I and insulin-like growth factor binding proteins-2 and -3 with prostate cancer invasion, progression, and metastasis. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  M. Kattan,et al.  Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis. , 2001, Urology.

[12]  M. Ittmann,et al.  Interleukin-6 is an autocrine growth factor in human prostate cancer. , 2001, The American journal of pathology.

[13]  A. Haese*,et al.  Human glandular kallikrein 2 levels in serum for discrimination of pathologically organ‐confined from locally‐advanced prostate cancer in total PSA‐levels below 10 ng/ml , 2001, The Prostate.

[14]  J. Blasko,et al.  Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer. , 2001, Urology.

[15]  J. Hugosson,et al.  Discrimination of prostate cancer from benign disease by plasma measurement of intact, free prostate-specific antigen lacking an internal cleavage site at Lys145-Lys146. , 2001, Clinical chemistry.

[16]  C. Roehrborn,et al.  Clinical predictors of spontaneous acute urinary retention in men with LUTS and clinical BPH: a comprehensive analysis of the pooled placebo groups of several large clinical trials. , 2001, Urology.

[17]  M. Kattan,et al.  Preoperative plasma levels of transforming growth factor beta(1) (TGF-beta(1)) strongly predict progression in patients undergoing radical prostatectomy. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  G. Yousef,et al.  The new human tissue kallikrein gene family: structure, function, and association to disease. , 2001, Endocrine reviews.

[19]  T. Tammela,et al.  Use of the complex between prostate specific antigen and alpha 1-protease inhibitor for screening prostate cancer. , 2000, The Journal of urology.

[20]  S. Loening,et al.  Ratio of alpha 1-antichymotrypsin--prostate specific antigen to total prostate specific antigen in prostate cancer diagnosis. , 2000, Anticancer research.

[21]  K. Slawin,et al.  Seminal plasma contains “BPSA,” a molecular form of prostate‐specific antigen that is associated with benign prostatic hyperplasia , 2000, The Prostate.

[22]  E. Metter,et al.  Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer. , 2000, The Journal of clinical endocrinology and metabolism.

[23]  T. Stamey,et al.  Preoperative serum prostate specific antigen does not reflect biochemical failure rates after radical prostatectomy in men with large volume cancers. , 2000, The Journal of urology.

[24]  M W Kattan,et al.  Pretreatment nomogram for predicting the outcome of three-dimensional conformal radiotherapy in prostate cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  M. Kattan,et al.  Correlation of preoperative plasma IGF-I levels with pathologic parameters and progression in patients undergoing radical prostatectomy. , 2000, Urology.

[26]  G. Wise,et al.  Cytokine variations in patients with hormone treated prostate cancer. , 2000, Journal of Urology.

[27]  T. Tammela,et al.  Insulin-like growth factor I is not a useful marker of prostate cancer in men with elevated levels of prostate-specific antigen. , 2000, The Journal of clinical endocrinology and metabolism.

[28]  T. Hill,et al.  Different proportions of various prostate‐specific antigen (PSA) and human kallikrein 2 (hK2) forms are present in noninduced and androgen‐induced LNCaP cells , 2000, The Prostate.

[29]  Y. Horiguchi,et al.  Serum interleukin 6 as a prognostic factor in patients with prostate cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[30]  T. Wheeler,et al.  A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue. , 2000, Cancer research.

[31]  H. Lilja,et al.  Sensitive and specific immunodetection of human glandular kallikrein 2 in serum. , 2000, Clinical chemistry.

[32]  W. Catalona,et al.  The combination of human glandular kallikrein and free prostate-specific antigen (PSA) enhances discrimination between prostate cancer and benign prostatic hyperplasia in patients with moderately increased total PSA. , 1999, Clinical chemistry.

[33]  D. Tindall,et al.  Use of human glandular kallikrein 2 for the detection of prostate cancer: preliminary analysis. , 1999, Urology.

[34]  J. Richie,et al.  Prediction of post-radical prostatectomy pathological outcome for stage T1c prostate cancer with percent free prostate specific antigen: a prospective multicenter clinical trial. , 1999, The Journal of urology.

[35]  D. Chan,et al.  Use of percentage of free prostate-specific antigen to identify men at high risk of prostate cancer when PSA levels are 2.51 to 4 ng/mL and digital rectal examination is not suspicious for prostate cancer: an alternative model. , 1999, Urology.

[36]  D. Tindall,et al.  Highly sensitive automated chemiluminometric assay for measuring free human glandular kallikrein-2. , 1999, Clinical chemistry.

[37]  H. Miyake,et al.  Elevation of serum levels of urokinase‐type plasminogen activator and its receptor is associated with disease progression and prognosis in patients with prostate cancer , 1999, The Prostate.

[38]  M. Kattan,et al.  Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  P. Boyle,et al.  Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. , 1999, Urology.

[40]  J. Simons,et al.  Characterization of the role of IL‐6 in the progression of prostate cancer , 1999, The Prostate.

[41]  H. Klocker,et al.  Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. , 1998, Cancer research.

[42]  M. Stampfer,et al.  Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. , 1998, Science.

[43]  C. Mantzoros,et al.  Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. , 1998, Journal of the National Cancer Institute.

[44]  A W Partin,et al.  Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. , 1998, JAMA.

[45]  M. Kattan,et al.  A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. , 1998, Journal of the National Cancer Institute.

[46]  V. Speights,et al.  Differential expression of insulin-like growth factor binding proteins in high versus low Gleason score prostate cancer. , 1998, The Journal of urology.

[47]  J. Hugosson,et al.  Characteristics of screening detected prostate cancer in men 50 to 66 years old with 3 to 4 ng./ml. Prostate specific antigen. , 1998, The Journal of urology.

[48]  G G Klee,et al.  Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial neoplasia and adenocarcinoma: a novel prostate cancer marker. , 1997, Urology.

[49]  D. Ornstein,et al.  Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. , 1997, JAMA.

[50]  E. Metter,et al.  Percentage of free prostate-specific antigen in sera predicts aggressiveness of prostate cancer a decade before diagnosis. , 1997, Urology.

[51]  F. Gauthier,et al.  Potential involvement of kallikrein hK2 in the hydrolysis of the human seminal vesicle proteins after ejaculation. , 1996, Journal of andrology.

[52]  W. Catalona,et al.  Longitudinal screening for prostate cancer with prostate-specific antigen. , 1996, JAMA.

[53]  R. Bast,et al.  Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. , 1996, Journal of the National Cancer Institute.

[54]  J. Thrasher,et al.  Immunohistochemical localization of insulin-like growth factor binding proteins 2 and 3 in prostate tissue: clinical correlations. , 1996, The Journal of urology.

[55]  U. Stenman,et al.  Purification and characterization of different molecular forms of prostate-specific antigen in human seminal fluid. , 1995, Clinical chemistry.

[56]  J. Simons,et al.  Interleukin-6: a candidate mediator of human prostate cancer morbidity. , 1995, Urology.

[57]  M. Stampfer,et al.  A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer. , 1995, JAMA.

[58]  T. Wheeler,et al.  Prostate specific antigen and gleason grade: an immunohistochemical study of prostate cancer. , 1994, The Journal of urology.

[59]  M. Papa,et al.  Serum insulin-like growth factor-binding protein-2 (IGFBP-2) is increased and IGFBP-3 is decreased in patients with prostate cancer: correlation with serum prostate-specific antigen. , 1993, The Journal of clinical endocrinology and metabolism.

[60]  T. Stamey,et al.  Elevated levels of insulin-like growth factor-binding protein-2 in the serum of prostate cancer patients. , 1993, The Journal of clinical endocrinology and metabolism.

[61]  O. Nilsson,et al.  Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. , 1991, Clinical chemistry.

[62]  J. Oesterling,et al.  Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia. , 1990, The Journal of urology.

[63]  B. Binder,et al.  Urokinase-type plasminogen activator as a marker for the formation of distant metastases in prostatic carcinomas. , 1988, The Journal of urology.

[64]  T. Stamey,et al.  Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. , 1988, The New England journal of medicine.

[65]  S. Loening,et al.  Prostate-specific antigen, its molecular forms, and other kallikrein markers for detection of prostate cancer. , 2002, Urology.

[66]  A. Lu,et al.  Preoperative serum prostate specific antigen levels between 2 and 22 ng./ml. correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng./ml. , 2002, The Journal of urology.

[67]  M. Kattan,et al.  Validation study of the accuracy of a postoperative nomogram for recurrence after radical prostatectomy for localized prostate cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  P. Schellhammer,et al.  Serum prostate specific antigen is a strong predictor of future prostate growth in men with benign prostatic hyperplasia. PROSCAR long-term efficacy and safety study. , 2000, The Journal of urology.

[69]  S. Loening,et al.  Molecular forms of prostate-specific antigen in malignant and benign prostatic tissue: biochemical and diagnostic implications. , 2000, Clinical chemistry.

[70]  T. Stamey,et al.  Examination of the 3 molecular forms of serum prostate specific antigen for distinguishing negative from positive biopsy: relationship to transition zone volume. , 2000, The Journal of urology.

[71]  R. Wolfert,et al.  "BPSA," a specific molecular form of free prostate-specific antigen, is found predominantly in the transition zone of patients with nodular benign prostatic hyperplasia. , 2000, Urology.

[72]  M. Kattan,et al.  Elevated levels of circulating interleukin-6 and transforming growth factor-beta1 in patients with metastatic prostatic carcinoma. , 1999, The Journal of urology.

[73]  W. Catalona,et al.  Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer. , 1998, The Journal of urology.

[74]  M. Saedi,et al.  Human glandular kallikrein, hK2, shows arginine‐restricted specificity and forms complexes with plasma protease inhibitors , 1998, The Prostate.

[75]  J. Thrasher,et al.  Insulin-like growth factor-binding protein-2 and -3 expression in benign human prostate epithelium, prostate intraepithelial neoplasia, and adenocarcinoma of the prostate. , 1996, The Journal of clinical endocrinology and metabolism.

[76]  A. Melman,et al.  Elevated plasma levels of TGF-beta 1 in patients with invasive prostate cancer. , 1995, Nature medicine.

[77]  P. Scardino,et al.  Association of transforming growth factor-beta 1 with prostate cancer: an immunohistochemical study. , 1993, Human pathology.

[78]  M. Steiner,et al.  Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. , 1992, Molecular endocrinology.

[79]  U. Stenman,et al.  A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. , 1991, Cancer research.

[80]  R. Babaian,et al.  Prostate‐specific antigen and prostate gland volume: Correlation and clinical application , 1990, Journal of clinical laboratory analysis.