Skeletal morbidity is a major problem in multiple myeloma. Histomorphometric studies have demonstrated that increased bone resorption can be present even in the absence of radiographic abnormalities. To overcome diagnostic problems in estimating the activity of bone resorption, new laboratory parameters that reflect bone metabolism accurately are urgently needed. We analyzed three parameters of osteoclastic bone destruction, i.e. deoxypyridinoline (Dpd) and amino-terminal collagen type-I telopeptide (NTx) in urine and carboxy-terminal telopeptide of type-I collagen (ICTP) in serum, of 75 patients with multiple myeloma (n = 57) or monoclonal gammopathy of undetermined significance (MGUS, n = 18) by ELISA/RIA techniques. Serum ICTP and urinary Dpd levels increased parallel to the stage of the disease and differed significantly (P< 0.001 for ICTP and P = 0.03 for Dpd) between MGUS, myeloma stage I, and myeloma in stages II and III according to Salmon and Durie. ICTP and Dpd were significantly elevated in patients with multiple myeloma in stage I compared to individuals with MGUS, while no significant difference was found for NTx. In this first study comparing the prognostic relevance of ICTP, NTx, and Dpd in multiple myeloma patients, ICTP was found to be a prognostic factor for overall survival in the Kaplan-Meier analysis (log-rank test: P < 0.03). Urinary NTx showed borderline significance (P = 0.05), and Dpd had no prognostic value in the survival analysis. Our data show that serum ICTP and urinary Dpd levels increase in parallel to advanced disease stages, and gives the first report on a significant difference in the bone resorption parameters ICTP and Dpd between individuals with MGUS and patients with myeloma in stage I. Among the bone resorption parameters studied serum ICTP was found to be the best prognostic factor for survival in multiple myeloma.
Background: The aim of this study was to compare the diagnostic utility of a new assay that measures all forms of prostate-specific antigen complexed (cPSA) to serum proteins except α2-macroglobulin with the assay of free PSA (fPSA) and the corresponding ratios to total PSA (tPSA) to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Methods: Serum samples were collected from 91 men without prostate disease and with normal digital rectal examination (controls), 144 untreated patients with PCa, and 89 patients with BPH. tPSA and cPSA were measured using the Bayer Immuno 1 system; fPSA and the additional tPSA were measured with the Roche Elecsys system. Results: The median cPSA/tPSA, fPSA/tPSA, and fPSA/cPSA ratios were significantly different between patients with BPH and PCa (78.7% vs 90.7%, 25.5% vs 12.1%, and 36.8% vs 14.3%, respectively; P <0.001). No correlations of cPSA and its ratios to tumor stage and grade were found. ROC analysis showed that cPSA was not different from tPSA (areas under the curve, 0.632 vs 0.568), whereas the cPSA/tPSA ratio was similar to the fPSA/tPSA ratio in increasing discrimination between BPH and PCa patients with tPSA concentrations in the tPSA gray zone between 2 and 10 μg/L (areas under the curve, 0.851 vs 0.838). Conclusions: Compared with tPSA, the fPSA/tPSA and cPSA/tPSA ratios both improve the differentiation between BPH and PCa comparably and are similarly effective in reducing the rate of unnecessary biopsies, whereas cPSA alone does not have any effect.
Our study was performed to evaluate the diagnostic usefulness of %fPSA alone and combined with an ANN at different PSA concentration ranges, including the low range 2-4 ng/ml, to improve the risk assessment of prostate cancer. A total of 928 men with prostate cancer and BPH without any pretreatment of the prostate in the PSA range 2-20 ng/ml were enrolled in the study between 1996 and 2001. An ANN with input data of PSA, %fPSA, patient's age, prostate volume and DRE status was developed to calculate the individual's risk before performing a prostate biopsy within the different PSA ranges 2-4, 4.1-10 and 10.1-20 ng/ml. ROC analysis and cut-off calculations were used to estimate the diagnostic improvement of %fPSA and ANN in comparison to PSA. At the 90% sensitivity level, %fPSA and ANN performed better than PSA in all ranges, enhancing the specificity by 15-28% and 32-44%, respectively. For the low PSA range 2-4 ng/mL, we recommend a first-time biopsy at an ANN specificity level of 90%. For PSA 4 -10 ng/mL, we recommend a first-time biopsy based on the ANN at the 90% sensitivity level. Use of an ANN enhances the %fPSA performance to further reduce the number of unnecessary biopsies within the PSA range 2-10 ng/ml. © 2002 Wiley-Liss, Inc. Key words: prostate cancer; prostate-specific antigen; receiver operating characteristic; neural network; prostate biopsyProstate cancer is the most common neoplasia among men in the Western world and PSA is recognized as the best marker for its early detection. 1 Due to lack of specificity, various techniques, such as PSA density, velocity and age-specific ranges, have been developed but are reported to be only partially successful. 1 Measurements of the molecular forms of PSA improve specificity over tPSA alone. 2,3 Approximately 20 -25% of all biopsies could be avoided using %fPSA in the tPSA range 4 -10 ng/ml 4,5 as well as for tPSA values lower than 4 ng/ml. 6 -8 For further enhancement of %fPSA specificity to differentiate between prostate cancer and benign prostate diseases, logistic regression 9,10 and ANNs have been successfully used. 11,12 Briefly, these models can predict diagnostic outcome using a variety of factors. Based on the data of 28 studies, both methods perform equally, especially for large cohorts. 13 However, ANNs can predict an outcome for an individual patient, which cannot currently be done with traditional statistics and they can better handle a greater number of variables with more nonlinear relations. 14 In a study of 656 men within the 4 -10 ng/ml tPSA range, Finne et al. 11 demonstrated an advantage of ANNs compared to logistic regression, avoiding approximately one-third of unnecessary biopsies at 95% sensitivity. For the lower tPSA range 2.6 -4 ng/ml, Babaian et al. 12 used a combination of 3 different ANNs and saved 63.6% of all unnecessary biopsies. To date, no study has evaluated 1 valid, clinically practicable ANN on %fPSA data for the whole tPSA range 2-10 or 2-20 ng/ml.We used data from a 5-year period of %fPSA measurements with only 1 assa...
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