A (-5, -7) proPSA based artificial neural network to detect prostate cancer.

OBJECTIVE The pro-forms of prostate specific antigen (-2,-5,-7 proPSA) and also %free PSA based artificial neural networks (ANN) have been suggested to enhance the discrimination between prostate cancer (PCa) and no evidence of malignancy (NEM). This study reports on the combined use of proPSA within a %free PSA based ANN to enhance specificity of PCa. METHODS Serum samples from 898 patients with PCa (n=384) or NEM (n=514) within the PSA range 1-10 microg/l were analyzed for PSA, free PSA and (-5,-7) proPSA (Roche assays). Patient data from two centers - taken first from the Swiss site of the ERSPC (Aarau) and from a referral population (Berlin) have been analyzed. Leave-one-out ANN models with the variables PSA, %fPSA, proPSA, prostate volume and status of digital rectal examination (DRE) were constructed and compared by receiver-operating characteristic (ROC) curve analysis. RESULTS (-5,-7) proPSA was only significantly different between NEM and PCa in the PSA range 4-10 microg/l. Within the PSA range 4-10 microg/l (Berlin group) the ANN including only the two variables %fPSA and proPSA could reach the same performance like the conventional ANN with PSA, %fPSA, age, prostate volume and DRE (both AUCs: 0.84) However, at 95% sensitivity all ANN could not improve specificity compared to %fPSA. CONCLUSIONS ProPSA as single parameter did not improve specificity over %fPSA whereas proPSA and %fPSA within an ANN in the PSA range 4-10 microg/l substituted prostate volume and DRE. At 95% sensitivity only ANN with prostate volume and DRE perform significantly better than %fPSA.

[1]  D. Chan,et al.  Clinical utility of proPSA and "benign" PSA when percent free PSA is less than 15%. , 2004, Urology.

[2]  Klaus Jung,et al.  Multicenter evaluation of an artificial neural network to increase the prostate cancer detection rate and reduce unnecessary biopsies. , 2002, Clinical chemistry.

[3]  S. Loening,et al.  A multicenter clinical trial on the use of (-5, -7) pro prostate specific antigen. , 2005, The Journal of urology.

[4]  Mesut Remzi,et al.  Novel artificial neural network for early detection of prostate cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  H. Klocker,et al.  Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml. , 2003, The Journal of urology.

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

[7]  V Kairisto,et al.  Software for illustrative presentation of basic clinical characteristics of laboratory tests--GraphROC for Windows. , 1995, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[8]  S. Holm.  A Simple Sequentially Rejective Multiple Test Procedure , 1979 .

[9]  U. Stenman,et al.  Estimation of prostate cancer probability by logistic regression: free and total prostate-specific antigen, digital rectal examination, and heredity are significant variables. , 1999, Clinical chemistry.

[10]  J. Oesterling,et al.  Prostate specific antigen: a decade of discovery--what we have learned and where we are going. , 1999, The Journal of urology.

[11]  W. Hoesel,et al.  Development and evaluation of an enzyme linked immunosorbent assay for the measurement of proPSA forms in sera , 2002 .

[12]  H. Klocker,et al.  Proenzyme psa for the early detection of prostate cancer in the 2.5-4.0 ng/ml total psa range: preliminary analysis. , 2003, Urology.

[13]  Dietmar Schnorr,et al.  An artificial neural network considerably improves the diagnostic power of percent free prostate‐specific antigen in prostate cancer diagnosis: Results of a 5‐year investigation , 2002, International journal of cancer.

[14]  Z. Zhang,et al.  Performance of a neural network in detecting prostate cancer in the prostate-specific antigen reflex range of 2.5 to 4.0 ng/mL. , 2000, Urology.

[15]  K. Jung,et al.  Factors influencing the ratio of free to total prostate‐specific antigen in serum , 1997, International journal of cancer.

[16]  O. Vorm,et al.  Identification of precursor forms of free prostate-specific antigen in serum of prostate cancer patients by immunosorption and mass spectrometry. , 2001, Cancer research.

[17]  Jerome P. Richie,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.

[18]  R. Wolfert,et al.  A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. , 1997, Urology.

[19]  P Finne,et al.  Predicting the outcome of prostate biopsy in screen-positive men by a multilayer perceptron network. , 2000, Urology.

[20]  B. G. Blijenberg,et al.  The value of (−7, −5)pro‐prostate‐specific antigen and human kallikrein‐2 as serum markers for grading prostate cancer , 2004, BJU international.

[21]  H. Cammann,et al.  Clinical utility of human glandular kallikrein 2 within a neural network for prostate cancer detection , 2005, BJU international.

[22]  Georg Bartsch,et al.  Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2 to 4 ng/ml prostate specific antigen. , 2004, The Journal of urology.

[23]  M. Peyromaure,et al.  Pro PSA : a "pro cancer" form of PSA? , 2005, Medical hypotheses.

[24]  A. Partin,et al.  An algorithm combining age, total prostate-specific antigen (PSA), and percent free PSA to predict prostate cancer: results on 4298 cases. , 1998, Urology.

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

[26]  W. Catalona,et al.  Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer. , 2004, Clinical chemistry.

[27]  P. Carpenter,et al.  A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. , 2001, Cancer research.