Effectiveness of radioimmunoassay of human prostate-specific acid phosphatase in the diagnosis and follow-up of therapy in prostatic carcinoma.

The radioimmunoassay of human prostate-specific acid phosphatase and the measurement of the catalytic activity of acid phosphatase using p-nitrophenyl phosphate as substrate were compared in the diagnosis and follow-up of therapy of prostatic cancer patients. We monitored 17 patients without metastases and eight patients with metastases for 12 months. We detected elevation of the catalytic activity of acid phosphatase [the upper limit for the reference range was mean + 2 (S.D.)] in 24% of the sera of all these patients (n = 25), and the concentration of prostate-specific acid phosphatase measured by radioimmunoassay [the upper limit for the reference range was mean + 3 (S.D.)] was elevated in 80% of these samples before therapy. The radioimmunological measurement of prostate-specific acid phosphatase was therefore more efficient in detecting prostatic cancer than was measurement of the catalytic activity. Favorable effects of the various forms of endocrine treatment were detected more clearly by the measurement of immunoassayable prostatic acid phosphatase than by the measurement of catalytic activity. Activation of the disease during various forms of endocrine treatment of prostatic carcinoma is possibly more efficiently signaled by radioimmunoassay than by measurement of catalytic activity.

Gene expression and prostate specificity of human prostatic acid phosphatase (PAP): evaluation by RNA blot analyses.

A fragment of a complementary DNA (cDNA) clone for human prostatic acid phosphatase (PAP) (EC 3.1.3.2.) was used to study the expression of corresponding mRNA in human tissues. The specificity of its expression in benign prostatic hyperplasia (BPH) and prostatic carcinoma tissues were indicated in RNA blot analyses. The PAPcDNA probe did not recognize any specific mRNAs in RNAs extracted from human liver cancer, lung cancer, pancreatic cancer, placenta, breast cancer cells (MCF-7), mononuclear blood cells or acute promyelocytic leukemia cells (HL-60), according to Northern blot analysis. mRNA for PAP was detected in the androgen-dependent human prostatic cancer cell line LNCaP, but not in the androgen-insensitive human prostatic cancer cell line PC-3. In contrast, lysosomal acid phosphatase (LAP) mRNA was detected in both of these human prostatic cancer cell lines. Our findings indicate a high specificity for the PAP gene in prostatic tissue. The mean abundance for the PAPmRNA expression was 0.26 for prostatic carcinoma samples (n = 11) and 0.46 for BPH samples (n = 8) according to slot-blot analysis. The differences observed between the different categories of prostatic tissue in PAPmRNA abundances call for additional studies on regulation of its expression.

The simultaneous radioimmunoassay of seven steroids in human spermatic and peripheral venous blood.

Seven unconjugated neutral steroids, including testosterone and some of its precursors and metabolites, were measured in the peripheral and spermatic venous blood males, employing specific radioimmunoassays after the fractionation of steroids on Lipidex-5000 (hydroxyalkoxypropyl Sephadex) microcolumns. Respective mean concentrations (ng/ml) and ranges of steroids estimated in peripheral and spermatic venous blood in all groups of patients were as follows: pregnenolone, 0.71 (0.29-2.39) and 10.97 (0.83-30.1); progesterone, 0.31 (0.02-0.57) and 10.17 (1.51-33.24); 17 alpha-hydroxyprogesterone, 1.04 (0.48-2.20) and 37.33 (1.68-141.00); androstenedione, 1.01 (0.26-2.65) and 11.87 (0.97-30.18); testosterone, 3.84 (0.63-10.64) and 255.1 (2.85-619.1); 5alpha-dihydrotestosterone, 0.19 (0.07-0.28) and 3.74 (0.04-9.71); androsterone, 0.27 (0.12-0.47) and 0.97 (0.20-2.15). Concentrations are similar to those estimated by mass spectrometry and protein binding assays, except for androsterone which has not previously been measured in this context. The low, but significant testicular secretion of both 5alpha-hydrotestosterone and androsterone suggests that these two steroids are testicular androgen metabolites, and that androgen metabolism in this tissue may be monitored by way of their measurement in spermatic vein blood.

Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. The Scandinavian BPH Study Group.

OBJECTIVES: To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia (BPH) is maintained over 2 years, and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months. METHODS: This was a multicenter, double-blind, placebo-controlled study involving 707 patients with moderate symptoms of BPH enrolled at 59 centers in five Scandinavian countries. Following enrollment and a 4-week single-blind placebo run-in period, patients were randomized to receive finasteride 5 mg once daily or placebo for 24 months. Urinary symptoms, urinary flow rate, prostate volume, postvoiding residual urinary volume, and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24. Interim physical and laboratory examinations were performed when indicated clinically. RESULTS: In finasteride-treated patients the total symptom score improved throughout the study, with a significant difference between the two groups at 24 months (P < or = 0.01), whereas in placebo-treated patients, there was an initial improvement in the symptom score but no change from baseline at 24 months. The maximum urinary flow rate decreased in the placebo group, but improved in the finasteride group, resulting in a between-group difference of 1.8 mL/s at 24 months (P < or = 0.01). The mean change in prostate volume was +12% in the placebo group versus -19% in the finasteride-treated group (P < 0.01). Finasteride was generally well tolerated throughout the 2-year study period. CONCLUSIONS: The efficacy of therapy with finasteride 5 mg in improving both symptoms and maximum urinary flow rate and reducing prostate volume has been shown to be maintained during 24 months while patients receiving placebo experienced a return to baseline or deterioration of these parameters during the study. These results demonstrate that finasteride can reverse the natural progression of BPH.

Ceftazidime vs. tobramycin for serious infections in urological patients.

A prospective, randomized study was undertaken to compare the efficacy and safety of tobramycin and ceftazidime in the treatment of serious infections in 77 urological patients. Of the 39 tobramycin-treated and 38 ceftazidime-treated patients, 74% and 82%, respectively, were cured clinically. Microbiological cure rates were 72% and 79%, respectively. Three patients treated with tobramycin and two treated with ceftazidime developed a significant superinfection. Both drugs were tolerated well. Because of potential ototoxicity and nephrotoxicity the use of aminoglycosides is less advantageous than ceftazidime for seriously infected urological patients.

[Finanseride in symtomatic benign prostatic hyeprtrophy. A 2-year placebo-controlled study]. / Finasterid ved symptomgivende benign prostatahypertrofi. Et toårs placebokontrolleret studie. Skandinaviske BPH-Studiegruppe.

The efficacy and safety of treatment with finasteride 5 mg daily for 24 months was assessed in this multicentre double blind placebo-controlled study including 707 patients with moderately symptomatic benign prostatic hyperplasia. Efficacy parameters were changes in voiding- and bladder storage symptoms assessed by a validated symptom score, changes in maximum urinary flow rate and changes in the prostate volume. In the finasteride patients, symptom score improved during the whole study with a significant difference between active treatment and placebo after 24 months (p < 0.01). Maximum flow rate increased in finasteride treated patients resulting in a difference between these and the placebo treated patients of 1.8 ml/s after 24 months (p < 0.01). Prostate volume was reduced by 19% in the finasteride treated patients versus an increase of 12% in the placebo treated patient group (p < 0.01). Finasteride was well tolerated. Patients receiving placebo progressed in symptoms after 16 months. Finasteride can halt the natural progression of moderately symptomatic BPH over a 24 month period.

Treatment of advanced prostatic carcinoma with a slow release depot LHRH analogue (Zoladex depot).

We treated 38 patients with newly diagnosed advanced prostatic cancer with monthly injections of a long acting depot preparation of a luteinizing hormone-releasing hormone superagonist (Zoladex depot). After 6 months' treatment 10% of the patients had complete objective regression, 77% had partial objective regression, 3% stable disease and 10% had objective progression. The LHRH analogue does not have the metabolic side effects of oestrogens. Depot luteinizing hormone-releasing hormone analogue may well become a preferred alternative for patients with advanced prostatic cancer.

Radioimaging of lymph node involvement in prostatic carcinoma.

We have previously shown that Tc-99m- or In-111-labelled derivatives of monoclonal antibodies against prostatic acid phosphatase can be used to reveal bone metastases of prostatic carcinoma. In this study, seven patients who were candidates for radical prostatectomy and two patients with bone metastases, were investigated to evaluate the applicability of this technique for preoperative staging of the patients. One milligram of monoclonal antibodies was injected bilaterally into the periprostatic space, and the patients were subjected to measurements by gamma camera. In one patient metastases were detected in the left para-aortic, iliac and obturator lymph nodes by this technique. The lesions incorporating radioactivity were confirmed to be metastases of prostatic cancer following staging pelvic lymphadenectomy. In the other four patients, radioimaging did not show any lymph node metastases, and this negative finding was confirmed at the operation. These early data indicate the possibility of preoperative staging of prostatic cancer by means of radiolabelled derivates of monoclonal antibodies, raised against prostatic acid phosphatase and injected into the periprostatic area.

Tumor markers. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

This chapter mainly deals with biochemical aspects on prostate specific antigen (PSA) and its clinical value. To a limited extent, also other tumor markers, which might be of importance in the evaluation of patients with prostate cancer are discussed. In serum, PSA exists in a free form or bound to antichymotrypsin. Interestingly, only 10% of PSA secreted from cancer cells seems to exist in a free form, as compared to 30% of PSA secreted from cells in benign prostatic hyperplasia (BPH). PSA seems to be closely, but not absolutely, related to tumor grade and stage. The mean value of PSA in patients with tumors dominated by Gleason grades 3 or below, was 10 ng/ml, compared to 29 ng/ml in those with higher grades. Patients with PSA values of 50 ng/ml or above almost exclusively had tumor of Gleason grades 4 or 5, and this limit usually reflected a generalized disease. Patients with PSA-values below 10 ng/ml almost exclusively had tumors confined to the prostate gland. In countries where screening for prostate cancer is believed in, it is important to understand that normal cut-off values are related to patient's age. The upper normal limit of males below 50 years of age should be set at 2.5 ng/ml, as compared to 6.5 ng/ml for men over 70 years of age. To improve the value of PSA determination and for scientific purposes, the standardization of the assay is urgently needed and under way. Prostate acid phosphatase (PAP) has in most centres been replaced by PSA. An elevated PAP value, as measured by the enzymatic method, invariably indicates a generalized disease and could thus be used as a complementary informative assay to PSA. Other markers have been used mainly to achieve additional prognostic information. In a multivariate analysis, the non-specific tumor marker neopterin, which reflects the host response to tumor antigens, was closely related to short-term prognosis. Neopterin was followed by thymidine kinase, a protein reflecting the cell turn-over and tumor grade. Also PSA at diagnosis seemed to add some prognostic information, whereas other markers did not.