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Objective: To evaluate the attitudes and practices related to prostate-specific antigen (PSA) screening for prostate cancer (PC) among Finnish physicians in 1999 and 2007., Materials and Methods: The first questionnaire survey was conducted in 1999 with a mailing to 102 urologists, 679 community physicians and 684 occupational health physicians identified from the membership files of three medical associations. The area of residence was divided into the study area of the Finnish PC screening trial and the rest of Finland. The second survey was carried out in 2007 targeting 168 urologists, 1039 community physicians and 938 occupational health physicians., Results: The response proportion was 48% in 1999 and 50% in 2007. In both rounds, urologists regarded PC as a more important public health issue than other physicians. On the other hand, the non-urologists considered early diagnosis and screening more important than the urologists. PC was rated by all physicians as a less important public health problem in 2007 than in 1999. A smaller proportion of urologists found routine PSA testing indicated for asymptomatic men, compared with other physicians (40% versus 74-60% in 1999, P < 0.001 and 35% versus 44-37% in 2007, P = 0.005). The proportion of physicians reporting regular PSA screening in asymptomatic men was reduced from 1999 to 2007 (from 18% to 9%, P < 0.0001)., Conclusion: Based on reported practices of Finnish urologists, community physicians and occupational health physicians, popularity of PSA testing declined between 1999 and 2007. Urologists found PSA testing among asymptomatic men justified less frequently than the other physicians.

Objective: To evaluate attitudes to prostate cancer screening with prostate-specific antigen (PSA) of men who complied with offered screening and those who declined it within the Finnish randomized population-based screening trial, and to compare general health-related quality of life (HRQL) between participants and non-participants., Subjects and Methods: Self-administered questionnaires were sent to 500 men randomized into the screening arm in 1996-99 within the Finnish component of the European Randomized Study on Screening for Prostate Cancer. A similar survey was conducted among 500 non-participants., Results: Response proportions among the screening participants and non-participants were 59% and 28%, respectively. Current smoking was less frequent (P < 0.05) among the participants. In terms of attitude, the participants regarded the prostate cancer study as more important and the invitation letter as more informative than the non-participants (P < 0.001). There was no clear difference in worry about treatment consequences. The most commonly given reasons for not participating included previous PSA testing (41%), forgetting the invitation (51%), or not wanting to think of prostate cancer (39%) and regarding possible further diagnostic examinations as unpleasant (28%). The non-participants had a lower mental health score (P < 0.001) than the participants in the RAND-36 Survey., Conclusion: Most men who chose not to attend screening had a positive attitude, but did not participate due to practical reasons. However, two-thirds of the non-participants indicated a willingness to participate in the next screening round.

Objectives: The percentage of free prostate-specific antigen (%fPSA) improves the diagnostic accuracy for prostate cancer when the serum level of total PSA (tPSA) is elevated. Approximately 14% of men with a tPSA below 3 microg/l have prostate cancer on biopsy, but the diagnostic value of %fPSA in such men is rather unknown. The purpose was to estimate the impact of %fPSA on future prostate cancer risk among men with a normal tPSA in prostate cancer screening., Subjects and Methods: The first round of the Finnish arm of the European Randomized Trial for Screening of Prostate Cancer in 1996 to 1999 comprised 20,793 men aged 55-67 yr. Screen-negative men (tPSA level below 3.0 microg/l, n=17,680) were followed up until the end of 2003. Cumulative risk of prostate cancer was calculated as a function of %fPSA., Results: During the median follow-up of 5.8 yr (range, 0-7.7 yr), 327 men were diagnosed with prostate cancer and 25% of them had a Gleason score of 7 or higher. Five years after the first screening, cumulative risk of prostate cancer was 1.7% (95%CI, 1.5-1.9%). Men with a %fPSA in the lowest quartile (<14.2%) showed a 6.9-fold risk compared with those with a level in the highest quartile (>23.7%)., Conclusions: In men with a low serum tPSA, a low %fPSA is a strong predictor of later diagnosis of prostate cancer.

We estimated the sensitivity of serum prostate-specific antigen (PSA) as a screening test for prostate cancer in the Finnish randomised, population-based prostate cancer screening trial. The study population consisted of 80,458 men aged 55-67 years identified from the national population registry and randomised to the screening or control arm of the trial. The screening algorithm was based on determination of serum PSA concentration. Test sensitivity was estimated based on interval cancer incidence during the first 4 years of follow-up among screening participants with a negative screening test. Interval cancers were defined as those occurring among men with a negative screening test. Altogether, 19 interval cancers were detected among 17,897 men with serum PSA < 3 ng/ml during the first screening interval. A further 5 cases were diagnosed among 811 men with PSA 3.0-3.9 ng/ml with a benign digital rectal examination or free total PSA ratio > or = 0.16. Test sensitivity based on serum PSA of 3 ng/ml was estimated to be 0.89 (95% confidence interval 0.84-0.93) and that based on PSA of 4 ng/ml combined with an ancillary test (digital rectal examination or free total PSA ratio in the PSA range 3.0-3.9) was 0.87 (0.82-0.92). Test sensitivity achieved with serum PSA in prostate cancer screening appears excellent in the context of a population-based effectiveness trial., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: Large randomized trials provide the only valid means of quantifying the benefits and drawbacks of prostate-specific antigen (PSA) screening, but the follow-up of ongoing studies is still too short to allow evaluation of mortality. We report here the intermediate indicators of screening efficacy from the second round of the Finnish trial., Experimental Design: The Finnish trial, with approximately 80,000 men in the target population, is the largest component in the European Randomized Study of Screening for Prostate Cancer. The first round was completed in 1996-1999. Each year 8,000 men 55-67 years of age were randomly assigned to the screening arm, and the rest formed the control arm. Men randomized to the screening arm in 1996 were reinvited 4 years later, in 2000, and PSA was determined., Results: Of the eligible 6415 men, 4407 (69%) eventually participated in the second round of screening. Of the first-round participants, up to 84% (3833 of 4556) attended rescreening. A total of 461 screenees (10.5%) had PSA levels of > or = 4 microg/liter. Altogether, 97 cancers were found, yielding an overall detection rate of 2.2% (97 of 4407). Seventy-nine cases were found among the 3833 second-time screenees (detection rate 2.1%) and 18 in those 574 men (3.1%) who had not participated previously. A PSA of > or = 4 microg/liter, but negative biopsy in the first screening round was associated with an up to 9-fold risk of cancer in rescreening relative to those with lower PSA levels at baseline. Ninety-one (94%) of all of the detected cancers were clinically localized., Conclusions: As surrogate measures of an effective screening program, both compliance as well as the overall and advanced prostate cancer detection rates remained acceptable. Men defined as screen-positive but with a negative confirmation of cancer at prevalence screen formed a high-risk group at rescreening.

Purpose: Early diagnosis of prostate cancer is a necessary, but not sufficient, prerequisite for an effective screening program aiming at mortality reduction. We compared tumor characteristics between the screening and control arms in the Finnish population-based screening trial., Experimental Design: The Finnish trial is the largest component in the European Randomized Study of Screening for Prostate Cancer. A total of 24,000 men aged 55-67 years were randomized to the screening arm, whereas 35,973 men formed the control arm during the first three screening years. At the time of invitation, 22,732 men were eligible for screening, and 15,685 (69%) participated. A prostate-specific antigen (PSA) concentration of > or ==" BORDER="0">4 micro g/liter was defined as a screening-positive finding., Results: The detection rate among screenees was 2.4% (377 of 15,685), whereas 0.6% (40 of 7,047) of nonparticipants in the screening arm and 0.3% (112 of 35,973) of the controls were diagnosed with prostate cancer during the first postrandomization year in the absence of screening. In the screening arm, 82% of the cancers were clinically organ confined compared with 65% in the control arm. Yet, both the absolute number and cumulative incidence of advanced cancer were higher in the screening arm. No differences were seen in the WHO grade distribution between the study groups. The median PSA was substantially lower among screen-detected cases (7.1 micro g/liter) than among nonattenders (15.7 micro g/liter) and controls (13.2 micro g/liter)., Conclusions: Our findings on intermediate indicators of PSA screening provide encouraging, yet inconclusive evidence for eventual mortality reduction.

Objectives: To study the factors determining new recurrences in patients with frequently recurring superficial bladder tumors., Methods: Of all 205 eligible patients, each received 5 weekly intravesical instillations of mitomycin C (MMC), with the first instillation given perioperatively. This was followed, according to randomization, by BCG instillations alone or by alternating instillations of interferon-alpha and BCG monthly for up to 1 year. Impact of 12 variables on time to first recurrence was retrospectively studied with the Cox multiple hazards regression and Kaplan-Meier analysis., Results: Type of regimen was the most significant factor determining new recurrences, with preceding recurrence rate being the most important prognostic factor. Timing of the first MMC was the third significant predictor in the main multivariate analysis, with more than a two-fold relative risk for a new recurrence if the first MMC instillation was given later than on day 0., Conclusion: Preceding recurrence rate, most accurately reflects, in patients with frequently recurring tumors, the inherent risk for new recurrences. This risk can be considerably reduced by use of an effective chemoimmunotherapy regimen, and in addition, by inclusion of an early perioperative chemotherapy instillation in such a regimen.

Purpose: Early detection of prostate cancer has been recommended for men with affected first-degree relatives despite the lack of evidence for mortality reduction. We therefore evaluated the impact of family history in the Finnish prostate cancer screening trial., Patients and Methods: Approximately 80,000 men were identified from the population register for the first screening round. Of the 32,000 men randomized to the screening arm, 30,403 were eligible at the time of invitation. A blood sample was drawn from the participants (n = 20,716), and serum prostate-specific antigen (PSA) was determined. Men with a PSA level > or = 4.0 ng/mL were referred for prostate biopsy. Information on family history was obtained through a self-administered questionnaire at baseline., Results: A total of 964 (5%) of the 20,716 screening participants had a positive family history, and 105 (11%) were screening-positive. Twenty-nine tumors were diagnosed, corresponding to a detection rate of 3.0% (29 of 964) and a positive predictive value of 28% (29 of 105). Of the 19,347 men without a family history, 1,487 (8%) had a PSA level > or = 4.0 ng/mL. The detection rate was 2.4% (462 of 19,347) and the positive predictive value was 31% (462 of 1,487). The risk associated with a positive family history was not substantially increased (rate ratio, 1.3; 95% confidence interval, 0.9 to 1.8). The results were not affected by the age of the screenee or age at diagnosis of the affected relative. The program sensitivity was 6% (29 of 491) (ie, selective screening policy would have missed 94% of cancers in the population). No differences were seen in the characteristics of screen-detected cancers by family history., Conclusion: Our findings provide no support for selective screening among men with affected relatives.

Background and Objective: Approximately 70% of the men with an elevated serum prostate-specific antigen (PSA) identified in prostate cancer screening do not have prostate cancer. Other available diagnostic variables may be utilized to reduce the number of false positive PSA results, but few algorithms for calculation of the combined impact of multiple variables are available. The objective of this study was to establish nomograms showing the probability of detecting prostate cancer at biopsy on the basis of total PSA, and the percentage of free PSA in serum, prostate volume and digital rectal examination (DRE) findings., Methods: In a randomized, population-based prostate cancer screening trial 10284 men aged 55-67 years were screened during 1996 and 1997 in two metropolitan areas in Finland. Results for men (n=758) with a serum PSA of 4-20 microg/l were used to establish the risk nomograms. Of these 200 (26%) had prostate cancer at biopsy., Results: Prostate cancer probability depended most strongly on the percentage of free PSA. Total PSA, prostate volume, and DRE also contributed to prostate cancer probability, whereas age and family history of prostate cancer did not. More false positive PSA results could be eliminated by using the multivariate risk model rather than the percentage of free PSA (p<0.001) or PSA density (p=0.003) alone., Conclusions: Wide variation in probability of detecting prostate cancer among screened men with a serum PSA of 4-20 microg/l was observed. The nomograms established can be used to avoid or defer biopsy in men with a low prostate cancer probability in spite of a serum PSA level exceeding 4 microg/l.

Objective: Lead-time in prostate cancer screening was estimated using data from the Finnish randomized, population-based trial., Methods: Lead-time was defined as the duration of follow-up needed to accrue the same expected number of incident prostate cancer cases in the absence of screening as detected in the initial screening round. Expected numbers were calculated using an age-cohort model., Results: Based on findings among 10,000 men screened in 1996-1997 with 292 screen-detected cancers, lead-time was estimated as approximately 5-7 years, depending on the reference rates used. This corresponds to a mean duration of the detectable preclinical phase (DPCP) of 10-14 years, given that the cancers were detected on average at the midpoint of the DPCP., Conclusions: The findings suggest that a screening interval substantially longer than the 2 years generally used for mammography screening is unlikely to cause a substantial loss of sensitivity. A long screening interval is further justified in order to diminish the extent of overdiagnosis, until mortality effects can be evaluated.

Objectives: The objective of the study is to evaluate the agreement of local and review urinary cytology in patients with newly diagnosed bladder cancer and in those being followed for their disease. In addition, the effect of the type of institution on agreement was determined., Methods: A total of 652 consecutive patients with bladder cancer from 19 institutions were evaluated; 575 (88.2%) of the patients had cytopathological sample available for central review and were eligible for analysis. One hundred and twenty nine (22.4%) of the patients had newly diagnosed bladder cancer, whereas the remaining 446 (77.6%) patients were under follow-up. A voided urine sample was obtained prior to transurethral resection of the bladder (TURB) or routine follow-up cystoscopy and split for culture and cytology. The cytopathological samples were first analysed by a local pathologist, and then re-analysed by a central reviewer. The agreement of cytological readings was determined by Kappa coefficient., Results: The sensitivities of local and review cytology in detection of primary bladder cancer were 38.8 and 31.0%, respectively. Recurrence was observed in 119 of the 446 (26.7%) patients under follow-up, of which both local and review cytology detected 21 (17.6%) cases. Specificities of local and review cytology were 97.6 and 96.6%, respectively. Overall agreement of urine cytology was good in patients with primary bladder cancer and moderate in those being followed for their disease as Kappa coefficients were 0.70 and 0.60, respectively. However, some disagreement was found when results were analysed according to type of institution, to type of primary tumour, and to result of follow-up cystoscopy. In patients with primary bladder cancer the Kappa coefficient was 0.86 (very good) in university hospitals and 0.36 (fair) in city hospitals. Accordingly, in patients under follow-up the Kappa coefficient was 0.65 (good) in university hospitals and 0.39 (fair) in district hospitals. Although the stage of primary tumour had no effect on agreement, agreement was moderate (Kappa coefficient 0.45) in those with low grade tumour and good (Kappa coefficient 0.67) in those with high grade tumour. In addition, Kappa coefficients were 0.65 (good) and 0.40 (fair) in those with and without recurrence at follow-up cystoscopy., Conclusions: Although overall agreement of routine cytology was from moderate to good in both diagnosis and monitoring of bladder cancer, there is some variation in agreement according to the type of institution. Accordingly, grade of primary tumour and the result of follow-up cystoscopy had effect on agreement reflecting subjectiveness and weak reproducibility of this test. This not only emphasises the need for continuing education and quality control for urine cytologic analysis, but also inspires the development of more objective tests.

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.

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.

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.

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.

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.

The value of angiography and fine needle aspiration biopsy in detecting, grading and staging of renal tumours was studied in 55 patients with renal tumours suspected clinically or on urography. 42 patients had malignant tumours. A correct angiographic diagnosis was made in 94% of the renal adenocarcinomas, the corresponding percentage for the aspiration biopsies was 71%. A combination of angiography and cytologic examination gave the correct diagnosis in 97%. In 4 cases of renal pelvic carcinoma the angiography showed extensive hydronephrosis only, the final diagnosis in these was cases achieved by fine needle aspiration biopsy. Angiographic staging of 30 renal adenocarcinomas was made according to the TNM system. The radiological staging was correct in 30% of T3 tumours, but in only 50% of T1 tumours and in one out of five T2 tumours. The difficulties seemed to be in determining the relation of tumours situated marginally near the renal capsule. Angiographic grading of the tumour was made according to the vascular pattern and the time of venous filling. Sparse vascularity and venous filling time of over 5 seconds was found in highly differentiated carcinomas and abundant vascularity and fast venous filling in neoplasms of moderate or low differentiation. The cytologic grading correlated fairly well with the histological grading. This study shows that angiography combine with fine needle aspiration biopsy provides good facilities for obtaining a correct diagnosis in renal tumours and preoperative information of the extent and degree of differentiation of renal malignant tumours.

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.

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)