Standardization of assay for cytokeratin-related tumor marker CYFRA21.1 in urine samples.

The determination of tumor markers in urine samples has been proposed as an effective diagnostic tool in bladder cancer. The aim of the present investigation was to validate in urine samples the assay of the CYFRA21.1 cytokeratin-related marker, the serum concentrations of which showed promising diagnostic utility in patients with bladder cancer. First-voided urine samples were collected from patients with different malignancies. CYFRA21.1 was assayed with a commercially available enzyme immunoassay (Boehringer Mannheim). Different centrifugation patterns, the use of different buffers and nonionic detergents, and pH variations were evaluated. We demonstrated that: (a) cells and cell debris contain a large amount of CYFRA21.1 and must be eliminated by centrifugation; (b) storage at -20 degrees C causes amorphous precipitate, which may aspecifically bind CYFRA21.1; (c) the latter behavior may be prevented by diluting fresh urine samples with phosphate buffer with nonionic detergent added; (d) pH variations within the range 4.9-8.2 do not significantly affect CYFRA21.1 assay results. Provided that samples are diluted with buffer containing nonionic detergent, the CYFRA21.1 assay showed good precision and accuracy characteristic in urine samples. We therefore propose a standard protocol for the collection of urine samples for CYFRA21.1 assay. In a preliminary clinical evaluation, CYFRA21.1 concentrations in 16 patients with primary bladder cancer were higher than in healthy subjects. In the urine collected in the follow-up of patients treated for bladder cancer, CYFRA21.1 tended to be higher in relapsed patients than in those without evidence of disease. These preliminary data induced us to extend the clinical trial to establish the actual role of this assay in routine use.

Longitudinal evaluation of prostate-specific antigen levels in a case-control study.

BACKGROUND: Over the last period--late 1970 to early 1990--the incidence of prostate carcinoma has nearly doubled, even though many more patients die with prostate cancer rather than of it. This finding, together with the slow growth of this tumor and the absence of a controlled trial, makes early diagnosis for this pathology quite questionable. On the other hand, it is well known that prostatic carcinoma is curable as long as it is intracapsular and that there is an ever increasing encouragement for early detection in all diseases. Since prostatic pathology increases its incidence as age advances, the first step in early diagnosis is to be able to discriminate between healthy, benign prostatic hyperplasia and cancer cases with a well-accepted and easily understandable method. The problem is to find the best method to do it. METHODS: We measured serum prostate-specific antigen (PSA) levels in 435 men participating in an epidemiological study, at first in 1987 and again in 1992. Men with PSA levels above 4 ng/ml (in 1992) were invited to undergo other diagnostic tests (digital rectal examination, transrectal ultrasonography, biopsy) in sequence on the basis of the results of the previous tests. The pathological findings from biopsies were the reference test to determine the presence or absence of prostate cancer (2.5% of the population). RESULTS: We divided PSA concentrations into three categories, according to the most used cutoffs ( < 4, 4-10, > 10 ng/ml); in the meantime, we took into account the change rate in PSA concentration in time, defined as delta PSA. By the comparison between PSA categories and delta PSA, we found out that the first one does not discriminate between benign and malignant pathologies, while the use of delta PSA strongly discriminates them (p < 0.001). CONCLUSION: On the basis of our results, we think that delta PSA might be the best parameter to indicate the presence of prostate cancer cases in an asymptomatic population.

Is serum PSA measurement a good test for early diagnosis of prostate cancer? Results of a pilot study and cost analysis.

Over the last years--late 1970s to early 1990s--the incidence of prostate carcinoma has nearly doubled, even though many more patients die suffering from prostate cancer than because of it. This finding, together with the slow growth of this tumor and the absence of a controlled trial that would suggest a benefit from screening, makes early diagnosis of this disease quite questionable. On the other hand, it is well known that prostatic carcinoma is curable as long as it is intracapsular, and that there is an ever increasing encouragement to early detection in all diseases. The costs of screening and the difficulty in balancing the benefits of screening against its negative effects, such as psychological impact and overtreatment, must be taken into account as well. In our opinion, one of the advantages of early diagnosis should be that the patients' quality of life improves, because the stage at diagnosis and, as a result, the number of patients suffering from bone metastasis decrease, and unknown benign pathologies can be cured. These observations are not at all negligible. Our study aims to demonstrate that by using PSA as an initial test, the screening costs are reasonable and the disease incidence is just as expected.