Soluble urokinase plasminogen activator receptor as a prognostic marker in men participating in prostate cancer screening.

BACKGROUND: The urokinase plasminogen activator (uPA) system is involved in tissue remodelling processes and is up-regulated in many types of malignancies. We investigated whether serum levels of different forms of soluble uPA receptor (suPAR) are associated with survival and in particular with prostate cancer and cardiovascular disease mortality. METHODS: Using time-resolved fluorescence immunoassays, we measured intact suPAR [suPAR(I-III)] and intact plus cleaved suPAR [suPAR(I-III) + suPAR(II-III)] and thus calculated the amount of suPAR(II-III) in serum samples from 375 men participating in a prostate cancer screening trial. A total of 312 men were free of prostate cancer and 63 men had prostate cancer diagnosed at the time of screening. The cohort was followed for 15 years. We assessed survival using Kaplan-Meier estimation and Cox proportional hazards regression. RESULTS: The mean age at blood sampling was 64 years. In total, 152 men died during follow-up. SuPAR(I-III) and suPAR(II-III) were significantly positively associated with mortality (P = 0.001 and P < 0.0001, respectively). In a Cox regression model adjusting for age and prostate cancer status, an increase in suPAR(I-III) and suPAR(II-III) by 1-unit (ln-scale) was associated with a hazard ratio (HR) of 2.26 [95% confidence interval (CI) 1.17-4.35] and 2.53 (95% CI 1.56-4.10), respectively. There was a trend towards an increased risk of death from prostate cancer in screening-detected prostate cancer patients with increased values of either suPAR form. However, this difference was not significant and the association disappeared after adjusting for age, tumour stage, tumour grade and prostate-specific antigen. Being in the highest quartile of any of the suPAR forms was associated with a highly significant increased risk of cardiovascular death, with HR adjusted for age of 3.27 (95% CI 1.38-7.73) for suPAR(I-III) quartile 4 versus quartile 1. Conclusions. High concentrations of serum suPAR(I-III) and suPAR(II-III) were associated with poor overall survival. The association was particularly strong for death from cardiovascular disease. No similar association was found for prostate cancer after adjustment for other prognostic factors.

Low IL-1alpha expression in bladder cancer tissue and survival.

OBJECTIVE: To investigate whether the previously reported association between IL-1alpha mRNA levels and survival in urinary bladder cancer remains in an extended patient material and to search a mechanism behind a possible antitumoral activity of IL-1alpha. PATIENTS AND METHODS: IL-1alpha mRNA levels were determined in 164 tumors with quantitative TaqMan PCR. RESULTS: A large variation was found in mRNA levels of IL-1alpha. We found, by immunohistochemistry, that IL-1alpha is expressed by tumor rather than stromal cells. In a univariate Cox proportional hazards model, low levels (median split) of IL-1alpha mRNA were associated with a relative hazard ratio (RHR) of 1.7 (95% CI: 1.0-2.9) for cancer-specific death (n=157); a restriction to muscle invasive tumors (n=63) resulted in an RHR of 1.8 (0.9-3.3). In bivariate analyses, adjustment for age, stage and grade respectively, decreased the RHR and the association between IL-1alpha expression and cancer-specific survival was not statistically significant. Which factors to regard as confounders remains unclear. CONCLUSIONS: Low levels of IL-1alpha mRNA expression are associated with an increased risk for cancer-specific death in the investigated material. However, confounding is an issue and to determine whether or not the observed association is causal, we need a defined mechanism and data from other studies.

The prevalence of loss of heterozygosity in chromosome 3, including FHIT, in bladder cancer, using the fluorescent multiplex polymerase chain reaction.

OBJECTIVE: To determine some of the genetic alterations involved in the pathogenesis and progression of transitional cell carcinoma of the bladder. Materials and methods In a population-based study, freshly frozen tissue was collected from all patients newly diagnosed with urinary bladder cancer in the Stockholm region during 1995-1996. The prevalence of loss of heterozygosity (LOH) was assessed at seven sites on chromosome 3, analysed in 151 patients, using a fluorescent multiplex polymerase chain reaction based on DNA from the tumour and peripheral blood. RESULTS: LOH was detected in 12.1% (at 3q25-26.2) to 22.1% (at 3p11-12) of the informative cases. Relatively frequent LOH was detected at 3p22-24.2 (21.6%), at 3p14.2 within FHIT (21.5%), and at 3p11-12 (22.1%). Of 151 tumours, 72 (47.7%) showed LOH at one or more loci on chromosome 3. LOH on chromosome 3 was weakly associated with tumour grade (P = 0.095), but not with tumour stage (P = 0.701). However, when the frequency of LOH was analysed individually at each site, the prevalence of LOH at 3p11-12 was closely correlated with higher tumour stage (P = 0.011). Replication errors were detected in only four of 151 (2.6%) tumours. Conclusion These findings suggest that the 3p11-12 locus may involve a putative candidate tumour-suppressor gene which might be associated with bladder tumour invasiveness. The FHIT gene locus showed a relatively high frequency of LOH even in Ta tumours.

Variation in percentage-free prostate-specific antigen (PSA) with prostate volume, age and total PSA level.

OBJECTIVE: To examine the correlation between prostate volume, patient age and total prostate-specific antigen (tPSA) with the percentage-free PSA (f/tPSA) in a population-based cohort of men with no prostate cancer and with a tPSA of < 10.0 ng/mL. SUBJECTS AND METHODS: Men who in 1988-1989, after randomized selection in the general population, participated in a population-based screening study for prostate cancer, were investigated. In all, 1622 of the men (aged 55-70 years) were considered free from prostate cancer and had a tPSA level of < 10.0 ng/mL. The f/tPSA and tPSA were determined in frozen sera from each individual, and related to prostate volume and age measured at the time of the study. The entire population was investigated, as were four subpopulations based on tPSA levels (< 2.0, 2.0-3.9, 4.0-6.9 and 7.0-9.9 ng/mL). Statistical calculations included multiple regression and correlation analysis. RESULTS: The f/tPSA level varied with prostate volume and age, but the decisive factor for this variation was the tPSA level. The closest correlation was in the tPSA interval 7.0-9.9 ng/mL, where volume and age together explained 47% of the variation in f/tPSA. Also, for men with tPSA levels in each of the intervals 2.0-3.9, 4.0-6.9 and 7.0-9.9 ng/mL, the f/tPSA increased with higher prostate volumes and age. In men with tPSA levels of < 2.0 ng/mL the f/tPSA was not affected by variations in prostate volume or age. CONCLUSION: The variation in f/tPSA with prostate volume, age and tPSA is highly dependent on the tPSA level. Volume and age in the tPSA interval 7.0-9.9 ng/mL can explain almost half the variation in f/tPSA, whereas this influence is insignificant in men with a tPSA of < 2.0 ng/mL.

Bladder cancer: allelic deletions at and around the retinoblastoma tumor suppressor gene in relation to stage and grade.

Inhibition of the retinoblastoma tumor suppressor gene (RB) is probably important in the pathogenesis of urinary bladder cancer. Little information is available concerning allelic loss on 13q11 to 13q32 and its relation to grade and stage. In a population-based study, freshly frozen tissue was collected from all new cases of urinary bladder cancer in the Stockholm region during 1995-1996. Here we report the occurrence of loss of heterozygosity (LOH) at seven sites in 13q11 to 13q32 as analyzed in 236 cases by a fluorescent multiplex PCR-based on tumor DNA and peripheral blood. For each site, about 30% of the cases were not informative because of homozygosity. Replication errors were detected in 4% (17 cases). LOH was found in 21 (at 13q11-12.1) to 32% (at 13q14.3 in RB) of the informative cases. A correlation was found between the prevalence of LOH at all observed loci and stage and grade, respectively, and it was statistically significant for 13q14.3. LOH at RB was found in Ta as well as grade 1 tumors. Also, a statistically significant correlation was found between the number of loci with LOH at 13q and tumor stage and grade, respectively. Typically an altered RB function is related to the expected clinical course of urinary bladder cancer, but allelic loss including the gene also occurs in low grade and low stage tumors. An altered RB function probably is not necessary for a malignant transformation of urothelial cells. The causal direction of the relation between the quantity of the deleted DNA and tumor aggressiveness is not clear.

Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL.

OBJECTIVES: To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. METHODS: A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). RESULTS: Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. CONCLUSIONS: The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.

Antibiotic prophylaxis for prostate biopsy: benefits and costs.

Transrectal ultrasound-guided core biopsy is a widely used method to diagnose prostate cancer. It is generally considered a safe procedure but the main concern is that significant complications such as infections do occur. To evaluate the effect of a combined two-dosage antibiotic prophylaxis with ciprofloxacin and metronidazole, a prospective study of 289 patients undergoing core-biopsy of the prostate was performed. Five patients (1.7%) developed urinary tract infection and all did recover without any further complications. The infection rate was significantly lower compared to our historic controls receiving no prophylaxis at all. This prophylactic regime resulted in a low infection rate and it was feasible from the patient perspective. The total cost of antibiotic medication and additional costs due to complications was 18 USD per patient and the cost-effectiveness compared to no prophylactic therapy at all was considered good.

Evaluation of clinical staging before cystectomy in transitional cell bladder carcinoma: a long-term follow-up of 276 consecutive patients.

OBJECTIVE: To evaluate retrospectively the clinical staging in a consecutive series of patients selected for cystectomy and to define its limitations with a view to possible improvements. PATIENTS AND METHODS: From 1979 to 1988, 276 patients with newly detected or recurring transitional cell carcinoma (TCC) of the bladder, were offered pre-operative irradiation (20 Gy) and cystectomy. The patients were assessed during 1995 and the outcome related to both clinical and surgical data. Survival was analysed on the basis of 'intention to treat'. Estimates of survival probabilities were calculated by the method of Kaplan and Meier. Differences in survival among subgroups were assessed using the log rank test and Cox stepwise regression analysis. RESULTS: Cancer-specific actuarial survival for the whole series was 68% at 5 years and 63% at 10 years. Survival was closely related to the depth of invasion found at surgery, clearly discriminating those with tumours confined to the bladder wall (< or = P3A) from those with extravesical extension (> or = P3B). The cancer-specific survival at 5 years for patients with < or = P3A tumours was 85% and for those with > or = P3B tumours was 50%. This important distinction was anticipated accurately using bimanual palpation before surgery, those patients with no palpable mass after transurethral resection of bladder tumour (TURBT) having an actuarial survival of 83%, and those with a residual mass a survival of 50% at 5 years. In the multivariate analysis, increasing clinical stage was the only pretreatment variable with significant prognostic value for survival. However, this variable was highly dependent on the palpatory findings after TURBT, the presence of a residual mass being a prerequisite for the clinical stage T3 in case of muscle-invasive tumour. CONCLUSION: Bimanual palpation remains crucially important in clinical staging, and there is a need for further standardization and refinement of this procedure.

Prostate-specific antigen (PSA), PSA density and age-adjusted PSA reference values in screening for prostate cancer--a study of a randomly selected population of 2,400 men.

Prostate cancer screening with DRE, TRUS, and PSA testing was offered to 2,400 randomly selected men 55-70 years old. Among 1,782 examined, 65 (3.6%) men with prostate cancer were diagnosed. The PSA results were correlated to the diagnosis, the men's age, and the prostate volume. Least square regression analysis was used to calculate the 95% upper confidence intervals for PSA in each year of age in men without prostate cancer. The PPV was calculated for: (i) PSA > 4 ng/ml, (ii) PSAD > 0.15, (iii) PSAD > 0.20 and (iv) age-adjusted PSA reference values. A significant correlation was found between PSA and prostate volume, between PSA and age, and between the prostate volume and age. The calculated annual growth of the prostate was 1.6% and the annual increase in PSA was 2.4%. The age-adjusted upper PSA reference values for the three age categories studied (55-59, 60-64 and 65-70 years) were 5.2, 5.8, and 6.7 ng/ml, respectively. The PPVs for PSA > 4 ng/ml, PSAD > 0.15, PSAD > 0.20, and the age-adjusted PSA reference values were 17%, 14%, 22%, and 27%, respectively. Age-adjusted PSA or PSAD may increase the PPV compared to PSA > 4 ng/ml. The detection rate is, however, inadequate. A PSA cut-off at 4 ng/ml could therefore be maintained in men 55-70 years old. The median PSA values and median prostate volumes calculated for men with benign findings may serve as a reference in future studies.

Phase II studies on prostate cancer.

OBJECTIVES: To evaluate different study designs and the general utility of phase II trials on prostate cancer. METHODS: Extensive literature studies and correspondance within the working group during 1 year were summarized in a preliminary manuscript. The manuscript was finalized at a 1 day meeting and is presented here as a consensus document. RESULTS: The main objectives of phase II studies are to assess whether a treatment is sufficiently active to justify comparative phase III studies, and to obtain further information on adverse reactions. Bidimensionally measurable lesions are traditionally studied, allowing objective criteria for response and progression to be applied. However, as skeletal metastases do not fulfill the criteria for such lesions, the majority of patients with metastatic prostate cancer are not eligible for traditionally-designed phase II trials. Therefore, ancillary response parameters, especially serum prostate-specific antigen (PSA), have been proposed for use. For the evaluation of adverse reactions, the criteria of the World Health Organization were proposed for use. A review of various statistical designs was presented, with a focus on their advantages and disadvantages in phase II trials. CONCLUSIONS: The role of PSA in phase II trials has not yet been firmly established. Further study of its correlation with other endpoints is needed. In future phase II trials, a shift to softer endpoints than traditionally used may enhance the process of evaluation of new antitumor drugs. Phase II studies may even be replaced by early phase III studies, especially in situations where new drugs do not have very heavy adverse effects.

Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population.

OBJECTIVE: To investigate the possible relationship between serum levels of prostate specific antigen (PSA), dihydrotestosterone (DHT), testosterone, sexual-hormone binding globulin (SHBG) and tumour stage, grade and ploidy in 65 cases of prostate cancer diagnosed in a screening study compared to 130 controls from the same population. PATIENTS, SUBJECTS AND METHODS: From a population of 26,602 men between the ages of 55 and 70 years, 2400 were selected randomly and invited to undergo screening for prostate cancer using a digital rectal examination, transrectal ultrasonography and PSA analysis. Among the 1782 attendees, 65 cases of prostate cancer were diagnosed. Each case was matched with two control subjects of similar age and prostate volume from the screening population. Frozen serum samples were analysed for PSA, DHT, testosterone and SHBG, and compared to the diagnosis and tumour stage, grade and ploidy. Comparisons between these variables, and multivariate and regression analyses were performed. RESULTS: There were significant differences in PSA level with all variables except tumour ploidy. DHT levels were slightly lower in patients with prostate cancer but the difference was not statistically significant. There was a trend towards lower DHT values in more advanced tumours and the difference for T-stages was close to statistical significance (P = 0.059). Testosterone levels were lower in patients with cancer than in the control group, but the differences were not significant. There was no correlation between testosterone levels, tumour stage and ploidy, but the differences in testosterone level in tumours of a low grade of differentiation compared to those with intermediate and high grade was nearly significant (P = 0.058). The testosterone/DHT ratio tended to be higher in patients with more advanced tumours. SHBG levels were lower in patients with cancer than in controls but the differences were not statistically significant. There were no systematic variations of tumour stage, grade and ploidy. Multivariate analysis showed that if the PSA level was known, then DHT, testosterone or SHBG added no further information concerning diagnosis, stage, grade or ploidy. Regression analysis on T-stage, PSA level and DHT showed an inverse linear relationship between PSA and DHT for stage T-3 (P = 0.035), but there was no relationship between PSA and testosterone. CONCLUSION: PSA was of value in discriminating between cases and controls and between various tumour stages and grades, but no statistically significant correlation was found for ploidy. If PSA level was known, no other variable added information in individual cases. Within a group, DHT levels tended to be lower among cases and in those with more advanced tumours. There was an inverse relationship between tumour volume, as defined by PSA level, and 5 alpha-reductase activity, as defined by DHT level, and the testosterone/DHT ratio. This trend was most obvious with T-stage. No systematic variation were found in the levels of testosterone or SHBG.

Cost-effectiveness analysis in early detection of prostate cancer: an evaluation of six screening strategies in a randomly selected population of 2,400 men.

Based on the findings in an early detection study for prostate cancer [Gustafsson et al.: J Urol 148:1827-1831, 1992] using digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate-specific antigen (PSA), a cost-effectiveness analysis was performed based on 6 screening strategies, namely: 1) DRE of all individuals; 2) TRUS of all individuals; 3) DRE, TRUS, and PSA analysis followed by reexamination of individuals with PSAs > or = 7 ng/ml; 4) DRE of individuals with PSAs of > or = 4 ng/ml; 5) TRUS of individuals with PSAs of > or = 4 ng/ml; 6) DRE and PSA analysis followed by TRUS on individuals with PSAs > or = 4 ng/ml. The detection rates of prostate cancer using these 6 strategies were 2.4%, 3.3%, 3.6%, 2.0%, 2.6%, and 3.2%, respectively. Except for costs per detected cancer, costs were also calculated per detected small cancer (< or = 1.5 cm) and per detected cancer treated for cure. The cost calculations were based on total costs, i.e., direct plus indirect costs. When the 6 strategies were compared, taking into account the detection rate of cancers treated for cure and cost-effectiveness with respect to cancers treated for cure, strategies 1), 2), 3), and 4) were ruled out as less favorable than the remaining 2 strategies. TRUS of individuals with PSAs > or = 4 ng/ml (strategy 5) was the most cost-effective strategy and detected 80% of the cancers actually treated for cure. Screening with DRE and PSA analysis followed by TRUS of individuals with PSAs > or = 4 ng/ml (strategy 6) had a somewhat lower cost-effectiveness, but detected 90% of the cancers treated for cure.

Psychological reactions in men screened for prostate cancer.

OBJECTIVE: To investigate the possible negative psychological impact of screening for prostate cancer with special focus on the impact of false positive and true positive test results. SUBJECTS AND METHODS: As part of an early detection study for prostate cancer psychological and psychophysiological reactions to various phases of the diagnostic procedures were examined in 2400 randomly selected men divided into various groups. Their psychophysiological reactions were assessed by measurements of serum cortisol and their psychological reactions by questionnaires directed at determining emotional states and sleep disturbance. In a stratified sample of the population (100 men) measurements were made at the time of the screening examination and again 2 weeks later. In patients undergoing biopsy (307 men) measurements were made 2 weeks after screening, but before they were informed of the biopsy results, and again 4 and 16 weeks after screening. RESULTS: Serum cortisol levels at the screening examination were higher than corresponding levels of a comparable sample of Swedish men during normal daily activity, indicating that an invitation to examination for prostate cancer per se might create emotional stress. Two weeks after the screening the elevated levels had decreased to normal. The highest cortisol levels were found in men who had undergone biopsy, immediately before they were informed of the results 2 weeks after screening. After they were informed, cortisol levels fell, regardless of the results of the biopsy. The patterns of emotional state and sleep disturbance were similar except that sleep disturbance was delayed. CONCLUSION: In screening programmes for prostate cancer it is important to define clearly the high-risk groups to minimize the risk of adverse psychological reactions in those subjects with a low risk of having the disease. The results also emphasize the need to reduce the number of false positive results by choosing diagnostic tests of high specificity. The interval between a test and informing the subject of the results should be minimized to decrease the duration of the increased emotional stress.

Imaging in the diagnosis and assessment of prognosis in localized prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

As part of a WHO consensus conference on diagnosis and prognostic parameters in localized prostate cancer, a working group of experts discussed the role of various modern imaging techniques. Special attention was focused on transrectal ultrasound (TRUS) in combination with biopsies, magnetic resonance imaging (MRI) using endorectal coil and recent advances in these techniques. Some experimental techniques, especially hormone receptor scintigraphy and positron emission tomography were also discussed and new results were presented. We concluded that MRI seems to be superior to other imaging techniques in the preoperative assessment of local tumor stage. TRUS defends its place in the diagnostic armament; it is easily combined with multiple biopsies, the results of which are important in the assessment of the biological aggressiveness of prostate cancer. The present development in the field of nuclear medicine may result in techniques for in vivo characterization of tumors and will most certainly have important implications for diagnosis of prostate cancer in the future.

Diagnostic methods in the detection of prostate cancer: a study of a randomly selected population of 2,400 men.

We investigated the value of digital rectal examination, transrectal ultrasonography and prostatic specific antigen (PSA) analysis as aids in general clinical practice and in the early detection of prostate cancer. Of a randomly selected population of 2,400 men 55 to 70 years old who were offered examination with digital rectal examination, transrectal ultrasound and PSA analysis, 1,782 (74%) accepted and prostate cancer was detected in 65 (3.6%). When the transrectal ultrasound results were also considered the detection rate of digital rectal examination (2.3%) was increased by 50% and the number of stage T2A or less tumors was doubled. At reexamination due to markedly high PSA values (7 micrograms/l. or more) only a few additional cancers (5%) were detected. However, it is noteworthy that 80% of the detected cancers were found among the subgroup with abnormal PSA values (4 micrograms/l. or more) and comprising 17% of the study population, which suggests the possibility of selecting a risk group at mass screening. Moreover, the positive predictive value increased from 4% (when only digital rectal examination was positive) to 71% for the combination of positive digital rectal examination, positive transrectal ultrasound and an increased PSA concentration (that is 7 micrograms/l. or greater).

Prognostic significance of mucosal aneuploidy in stage Ta/T1 grade 3 carcinoma of the bladder.

In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma. Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox's proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma.

Detection of DNA alterations in human bladder tumors by DNA fingerprint analyses.

DNA fingerprint analyses were used to examine the constitutional and tumor DNA from 22 bladder tumor patients. DNA alterations, such as loss of bands, new bands, and intensity shifts were observed in 10 of the 22 patients. The most frequent DNA alteration, occurring in 80% of the patients, was a complete loss of one or several bands. Fingerprint abnormalities were present both in low-malignant superficial tumors and in high-malignant invasive tumors, but were also lacking in the latter group. Apparently no relationship exists between fingerprint abnormalities and gross chromosomal aberrations or the proportion of S-phase cells as measured by flow cytometry or development of recurrent tumors during a limited observation period. Thus, whether fingerprint aberrations express genetic alterations directly involved in the malignancy potential of bladder carcinoma remains an open question.

[A study on prostatic cancer. The patient can decide himself: medical or surgical treatment]. / Studie om prostatacancer. Patienten kan få bestämma själv: medicinsk eller kirurgisk behandling.

In a multicentre study, 101 consecutive patients with advanced prostate cancer were offered the choice of orchiectomy or treatment with an LHRH analogue. Together with the cancer diagnosis the patients were given verbal information about the treatment alternatives, and detailed written information to peruse at home. One week later the patients informed the attending physicians of their choice. Information as to the reasons for the patients' choice, and their views on their choice after the start of treatment were elicited by questionnaire. Of the 101 patients, 48 chose orchiectomy, and 48 treatment with an LHRH analogue, five patients being excluded owing to their inability to decide. Mean age was about 73 years in both treatment groups, and about two thirds of each group lived with a partner. The level of education was higher among those who chose medical treatment. The predominant reasons for the choice of treatment were as follows: Orchiectomy, simpler (31 per cent), troublesome having to have monthly injections (19 per cent), simple to perform (15 per cent); medical treatment, possibility of change in treatment (27 per cent), simpler (17 per cent), fear of surgery (15 per cent). Most patients in both groups had no difficulty deciding, chose quickly, felt sure about their choice, appreciated the opportunity of choosing, and had discussed their choice with their partners or intimates. Three months after the start of treatment, almost all patients were still satisfied with their choice, and had no wish to change their choice even if that were possible.(ABSTRACT TRUNCATED AT 250 WORDS)