Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial.

Specificity constitutes a component of validity for a screening test. The number of false-positive (FP) results has been regarded as one of major shortcomings in prostate cancer screening. We estimated the specificity of serum prostate-specific antigen (PSA) determination in prostate cancer screening using data from a randomised, controlled screening trial conducted in Finland with 32 000 men in the screening arm. We calculated the specificity as the proportion of men with negative findings (screen negatives, SN) relative to those with negative and FP results (SN/(SN+FP)). A SN finding was defined as either PSA

Prostate cancer screening within a prostate specific antigen range of 3 to 3.9 ng./ml.: a comparison of digital rectal examination and free prostate specific antigen as supplemental screening tests.

PURPOSE: Performing biopsy in all men with a serum prostate specific antigen (PSA) of 3 to 3.9 ng./ml. increases the sensitivity of prostate cancer screening compared with a PSA cutoff of 4 ng./ml. but decreases specificity and may contribute to over diagnosis. Therefore, we evaluated the detection rate and specificity attributable to digital rectal examination and percent free PSA within the PSA range of 3 to 3.9 ng./ml. MATERIALS AND METHODS: Serum PSA was determined in 20,716 participants in the Finnish population based screening trial. Supplementary digital rectal examination was offered to men with a PSA of 3 to 3.9 ng./ml. during 1996 to 1998 (protocol 1). Those with a suspicious digital rectal examination finding were referred for biopsy. The screening algorithm was modified by substituting percent free PSA for digital rectal examination with a cutoff of 16% as a biopsy criterion in 1999 (protocol 2). In addition, biopsies were performed in all men with PSA 4 ng./ml. or greater. RESULTS: A total of 23 cancers (2.9%) were detected by digital rectal examination among 801 men, while percent-free PSA resulted in the diagnosis of 13 cases (4.8%) among 270 men with a PSA of 3 to 3.9 ng./ml. The detection rate of tumors with a Gleason score of 5 or greater increased from 1.6% (13 of 801 cases) to 4.4% (12 of 270) in the modified screening program. The PSA cutoff of 3 ng./ml. alone showed 88.6% and 87.5% specificity in protocols 1 and 2 but specificity increased to 93.3% and 91.7% using digital rectal examination and percent free PSA, respectively. CONCLUSIONS: Using percent free PSA increased the detection rate of aggressive disease compared with digital rectal examination and provided higher specificity than PSA alone.

Predicting the outcome of prostate biopsy in screen-positive men by a multilayer perceptron network.

OBJECTIVES: To assess whether an artificial neural network (multilayer perceptron, MLP) and logistic regression (LR) could eliminate more false-positive prostate-specific antigen (PSA) results than the proportion of free PSA in a prostate cancer screening. METHODS: MLP and LR models were constructed on the basis of data on total PSA, the proportion of free PSA, digital rectal examination (DRE), and prostate volume from 656 consecutive men (aged 55 to 67 years) with total serum PSA concentrations of 4 to 10 ng/mL in the randomized population-based prostate cancer screening study in Finland. The MLP and LR models were validated using the "leave-one-out" method. RESULTS: Of the 656 men, 23% had prostate cancer and 77% had either normal prostatic histology or a benign disease. At a 95% sensitivity level, 19% of the false-positive PSA results could be eliminated by using the proportion of free PSA versus 24% with the LR model and 33% with the MLP model (P < 0.001). At 80% to 99% sensitivity levels, the accuracy of the MLP and LR models was significantly higher than that of the proportion of free PSA. At 89% to 99% sensitivities, the accuracy of the MLP was higher than that of LR (P

Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer.

PURPOSE: The combination of interferon alfa-2a (IFNalpha2a) plus vinblastine (VLB) induces objective tumor responses in patients with advanced renal cell cancer. However, no prospective randomized trial has shown that this treatment prolongs overall survival. We compared overall survival after treatment with IFNalpha2a plus VLB versus VLB alone in patients with advanced renal cell cancer. PATIENTS AND METHODS: We prospectively randomized 160 patients with locally advanced or metastatic renal cell cancer to receive either VLB alone or IFNalpha2a plus VLB for 12 months or until progression of disease. In both groups, VLB was administered intravenously at 0.1 mg/kg every 3 weeks, and in the combination group IFNalpha2a was administered subcutaneously at 3 million units three times a week for 1 week, and 18 million units three times a week thereafter for the second and subsequent weeks. For patients unable totolerate IFNalpha2a at 18 million units per injection, the dose was reduced to 9 million units. RESULTS: Median survival was 67.6 weeks for the 79 patients receiving IFNalpha2a plus VLB and 37.8 weeks for the 81 patients treated with VLB (P =.0049). Overall response rates were 16. 5% for patients treated with IFNalpha2a plus VLB and 2.5% for patients treated with VLB alone (P =.0025). Treatment with the combination was associated with constitutional symptoms and abnormalities in laboratory parameters, but no toxic deaths were reported. CONCLUSION: The combination of IFNalpha2a plus VLB is superior to VLB alone in the treatment of patients with locally advanced or metastatic renal cell carcinoma. This is the first study to demonstrate that survival can be prolonged by using IFNalpha2a for these patients.

European randomized study of prostate cancer screening: first-year results of the Finnish trial.

Approximately 20000 men 55-67 years of age from two areas in Finland were identified from the Population Registry and randomized either to the screening arm (1/3) or the control arm (2/3) of a prostate cancer screening trial. In the first round, the participation rate in the screening arm was 69%. Of the 5053 screened participants, 428 (8.5%) had a serum prostate-specific antigen (PSA) concentration of 4.0 ng/ml or higher, and diagnostic examinations were performed on 399 of them. A total of 106 cancers were detected among them corresponding to a positive predictive value of 27%, which is comparable with mammography screening for breast cancer. The prostate cancer detection rate based on a serum PSA concentration of 4.0 ng ml(-1) or higher was 2.1%. Approximately nine out of ten screen-detected prostate cancers were localized (85% clinical stage T1-T2) and well or moderately differentiated (42% World Health Organization (WHO) grade I and 50% grade II), which suggests a higher proportion of curable cancers compared with cases detected by other means.

Polyestradiol phosphate (160 mg/month) or LHRH analog (buserelin depot) in the treatment of locally advanced or metastasized prostatic cancer. The Finnprostate Group.

The clinical efficacy, cardiovascular complications and mortality of polyestradiol phosphate (PEP) 160 mg/month i.m. were compared with the luteinizing hormone releasing hormone (LHRH) analog, buserelin, in a prospective, randomised multicentre study including 147 patients with prostatic cancer. The cumulative non-progression rate at three years was 0.53 in the PEP group and 0.70 in the LHRH group. The mortality from cardiovascular diseases was the same in the two treatment groups. The parenterally given PEP was not associated with an increased risk of cardiovascular complications. The dosage of PEP 160 mg monthly seems, however, to be insufficient in the treatment of prostatic cancer.

Integrin distributions in renal cell carcinomas of various grades of malignancy.

We studied 41 renal cell carcinomas, classified according to histologic grades G1 through G3, by indirect immunofluorescence microscopy using a panel of monoclonal antibodies (MAb) against various integrin subunits, and the basement membrane (BM) components laminin and collagen type IV. Selected cases also were immunostained using the avidin-biotin-complex method. The alpha 3 and beta 1 integrin subunits were detected in tumor cells of all the carcinomas. All G1 carcinomas, like normal tubular epithelial cells, expressed the alpha 6 subunit, whereas it was lacking in 20% and 40% of G2 and G3 carcinomas, respectively. Furthermore, when alpha 6 was expressed, a lack of basally polarized organization of the subunit, coupled with disorganization of the BM components, correlated with histologic grade. Another feature that appeared to characterize the more anaplastic tumors was their high level (80%) of the alpha v subunit expression as compared with its absence in the G1 carcinomas. Stromal myofibroblasts, identified by double-labeling with anti-myosin, were often characterized by the expression of the alpha 1, alpha 3, alpha 5 and beta 1 subunits. These results indicate that changes in integrin expression in renal cell carcinomas may be correlated with their degree of histologic malignancy.

Can fine needle aspiration biopsy detect incidental prostatic carcinoma (T1) prior to TUR?

The purpose of this study was to find out whether randomly taken fine needle aspiration biopsy (FNA) can detect incidental prostatic carcinoma prior to transurethral resection (TUR) and what are the effects of local tumor stage and grade on detection rate. Biopsies were taken from 344 patients, who came to hospitals for elective TUR without clinical evidence of prostatic carcinoma. Histologic examination of the TUR material showed prostatic carcinoma in 49 cases (14%). Sufficient material for cytologic examination was found in 343 cases. Of the 16 cases of T1a carcinoma in histologic examination, cytology found only 1, which was a G3 carcinoma. Of 33 T1b carcinoma in histologic examination, cytology found 6 and an additional 7 were suspect findings. Out of 6 G3 tumors in histologic examination, cytology showed 4. In our hands the proportion of false-negative cytologic findings in randomly taken FNA was so large that routine use of random FNA prior to TUR or as a screening procedure cannot be recommended, but positive FNA finding can be regarded as cancer.

Orchiectomy versus oestrogen in the treatment of advanced prostatic cancer.

The primary clinical efficacy of orchiectomy and the combination therapy of intramuscular polyoestradiol phosphate 80 mg monthly and oral ethinyl oestradiol 0.15 mg daily was evaluated by progression and cancer mortality rates in a series of 277 prostatic cancer patients representing part of the Finnprostate study. After a follow-up of 5 years there was a significant difference between the groups in terms of progression rate and prostatic cancer deaths. The oestrogen combination was more effective in delaying progression of the disease. The overall mortality rate was similar in both groups. About one-third of the patients were alive after 5 years.

Intravesical chemotherapy (mitomycin C) versus immunotherapy (bacillus Calmette-Guérin) in superficial bladder cancer.

Both intravesical mitomycin C (MMC) and bacillus Calmette-Guérin (BCG; Pasteur strain F) were effective in the present prospective randomized multicenter study consisting of 91 patients with frequently recurrent superficial (Ta-T1) bladder cancer. The result was in favour of BCG, as shown by the measurements with complete response (CR), disease-free interval and recurrence rate. CR of 58% with MMC and 40% with BCG were reached in 22 instillation series on carcinoma in situ of 18 patients. Due to side effects, MMC instillations were discontinued in 8.6%, and BCG instillations in 19.6%, respectively. After the 2-year follow-up also 1 case of pulmonary tuberculosis occurred in the BCG group.

Efficacy and side-effects of prazosin as a symptomatic treatment of benign prostatic obstruction.

This randomized double-blind crossover trial was conducted to assess the effects of prazosin, an alpha 1-adrenoceptor blocking drug, on the voiding of 35 patients with benign prostatic obstruction. Maximum and mean flow rates, residual urine, blood pressure and heart rate were measured at baseline and 2, 4, 6, and 8 weeks after starting the treatment with placebo or prazosin. At 4 weeks the treatments were switched over. The patients filled micturition charts at home and scored their voiding associated feelings. The maximum and mean flow rates increased significantly during prazosin treatment, as also did the maximum and mean voided volumes. Residual urine decreased and voiding improved subjectively but these changes were not statistically significant. Blood pressure was lowered and heart rate increased. Prazosin caused postural dizziness more often than placebo. Prazosin seems to offer an alternative to improve voiding in some patients with prostatic obstruction.

Binding of the blood group-reactive lectins to human adult kidney specimens.

The binding of a panel of blood group-reactive lectins to frozen sections of human kidney was studied with a special emphasis on reactivity with endothelia and basement membranes. The blood group A-reactive lectins, all specific for alpha-D-N-acetylgalactosamine (GalNAc), Helix aspersa (HAA), Helix pomatia (HPA), and Griffonia simplicifolia I-A4 (GSA-I-A4) agglutinins bound to the endothelium in specimens with blood groups A and AB. In other samples, these lectins reacted predominantly with tubular basement membranes, as well as with certain tubules. Both Dolichos biflorus (DBA) and Vicia villosa agglutinins (VVA), reported to react with blood group A1 substance, failed to reveal endothelia in most specimens, but bound differently to tubules in all blood groups. The blood group B-reactive lectins, specific for alpha-D-galactose (alpha-Gal) or GalNAc, respectively, GSA-I-B4 and Sophora japonica agglutinin (SJA), bound to the endothelia in specimens from blood group B or AB and in other specimens bound only to certain tubules. Among the blood group O-reactive lectins, specific for alpha-L-fucose (Fuc), Ulex europaeus I agglutinin (UEA-I) conjugates, but not other lectins with a similar nominal specificity, bound strongly to endothelia in specimens with blood group O. The UEA-I conjugates bound distinctly more faintly to endothelia in specimens of other blood groups. The present results indicate that lectins, binding to defined blood group determinants, react with endothelia in specimens of the respective blood group status. Furthermore, they suggest that basement membranes and some tubules in the human kidney show a distinct heterogeneity in their expression of saccharide residues, related to their blood group status.

A controlled, double-blind, cross-over study of terodiline in motor urge incontinence.

In a placebo-controlled, randomized, double-blind, cross-over study, terodiline (50 mg/d) was compared with emepronium (600 mg/d) in 20 patients with motor urge incontinence. Evaluation of clinical efficacy was based on changes in micturition pattern, flow measurements, residual urine, cystometry and patient preferences, and safety on adverse reactions, blood chemistry, urine examinations and ECG. The number of voluntary micturitions decreased from a mean of 21.5 per 48 h on placebo by 1.6 on terodiline and 2.8 on emepronium. Involuntary micturitions decreased from 3.6 per 48 h by 1.3 on both treatments (p less than 0.05). The maximal flow rate decreased from a mean of 24.5 ml/sec to 19.6 ml/sec on emepronium and increased to 25.4 ml/sec on terodiline. Residual urine decreased from a mean of 54 ml to 49 ml on terodiline and increased to 60 ml on emepronium. Volume at first desire to void in the supine position increased on emepronium by 44 ml (p less than 0.05) and on terodiline by 3 ml, on the upright position by 11 ml and 18 ml, respectively. Bladder capacity increased in the supine position on emepronium by 32 ml and decreased on terodiline by 8 ml, in the upright position increased by 9 ml and 5 ml, respectively. The bladder pressure at first desire to void in the supine position increased on emepronium by 2 cmH2O, and decreased on terodiline by 2 cmH2O. The intravesical pressure at strong desire to void decreased on emepronium by 6 cmH2O and on terodiline by 7 cmH2O, in the upright position by 2 cmH2O and 1 cmH2O, respectively. 39% of the patients preferred terodiline, 39% emepronium and 22% placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Early results of the Finnish Multicentre Study of Prostatic Cancer (Finnprostate).

Four hundred and four prostatic cancer patients diagnosed in the years 1979-1982 in nine Finnish hospitals have been followed up for a mean period of three years. The aim of this study is to evaluate the situation of this malignancy in the Finnish male population and to discuss the diagnostic procedures and treatment modalities. In one fifth of the patients the carcinoma was as incidental finding on microscopical examination of tissue removed by transurethral resection or enucleation for presumed benign prostatic hyperplasia. At the diagnostic moment 69% of the tumours were locally advanced beyond the prostatic capsule and one third of all cases had metastasized. 134 out of 404 (33%) have died and 45% of these of prostatic cancer. Survival was adversely affected by the tumour differentiation grade. In non-metastasized cases the local extent of the tumour had no notable effect on prognosis. Some early comparisons are made between orchidectomy and oestrogen therapy.