Assessment of endpoints for clinical trials for localized prostate cancer.

Objectives: The AUA Practice Guidelines Panel convened to address the issue of appropriate endpoints for assessment of treatment modalities for localized carcinoma of the prostate.

Methods: A review of the literature and the design of existing clinical trials produced a consensus, which was presented to and critiqued by the members of the general conference.

Results: The pitfalls associated with identification of local failure endpoints were discussed, and the more accurate endpoints of freedom from metastatic progression and overall survival were recognized.

Prostate size in hypogonadal men treated with a nonscrotal permeation-enhanced testosterone transdermal system.

Objectives: This study examined the effects of testosterone replacement using a nonscrotal testosterone transdermal (TTD) system on prostate size and prostate-specific antigen (PSA) levels in hypogonadal men.

Methods: As part of an open-label, multicenter study, prostate volume as measured by transrectal ultrasound and PSA were assessed in 29 hypogonadal men during treatment with intramuscular testosterone enanthate (+TE), followed by 8 weeks of androgen withdrawal (-T), and then during 1 year of therapy with Androderm Testosterone Transdermal System, a nonscrotal permeation-enhanced TTD system (+TTD).

Results: Mean prostate volume decreased significantly from the +TE period (17 g) compared with the -T period (14 g) (P < 0.

Leukotriene D4-induced signalling events in human epithelial cells: G alpha i3 activation and translocation.

Our model of LTD4-induced signal transduction in epithelial cells is summarised in Figure 2. Extending what is already known about LTD4 signalling in epithelial cells, we identified the Gi3-protein as the crucial PTX sensitive G-protein and found that it is translocated to what might be a cytoskeletal fraction. This finding suggests a subtle response to LTD4, mediated via the bifurcation at the alpha/beta gamma junction.

[Delayed therapy of clinically localized prostatic carcinoma. Experiences of the Karolinska Hospital].

From 1978 to 1982, 172 patients with T1-3, Nx, M0 prostate cancer were included in a surveillance protocol with deferred treatment on symptomatic progression. The median age at diagnosis was 68 (38-89) years. The disease-specific survival at 10 years was 80% for the total series, 84% for the subgroup with T1-2 tumors, and 92% for patients with T1-2 tumors diagnosed when the patients were old less than 70 years.

Elevated nitric oxide in the urinary bladder in infectious and noninfectious cystitis.

Objectives: A role for nitric oxide (NO) has been suggested in inflammation and host defense. At higher concentrations, this gas shows cytotoxic effects that may be directed against microorganisms, tumor cells as well as host cells. The aim of the present study was to study the relationship between bladder mucosal inflammation and local production of NO.

Leukotriene D4-induced activation and translocation of the G-protein alpha i3-subunit in human epithelial cells.

The present results show that stimulation of Intestine 407 epithelial cells with LTD4 (Leukotriene D4) triggers a rapid activation of the pertussis-toxin-sensitive Gi3-protein and a simultaneous translocation of its alpha-subunits to a crude cytoskeletal fraction. The activation of G alpha i3, which was measured as the GTP/ GDP exchange ratio, peaked about 15 s after the addition of LTD4. Western blot analyses of subcellular fractions showed that G alpha i3-subunits accumulated in the cytoskeletal fraction and decreased in the membrane fraction, and the decrease was most marked 15 s after the exposure to LTD4.

Bias due to observation of different parts of a nonconstant hazard curve over time.

Objectives: Uncontrolled data often have to be used in clinical decision marking and in the planning of clinical trials. When such data are used as a basis for comparing different treatment strategies, they tend to generate sources of bias such as inconsistent patient selection, misrepresentation, and measurement errors. A rational usage of uncontrolled data requires identification and handling of different systematic errors when comparing different treatment strategies.

Waning sexual function--the most important disease-specific distress for patients with prostate cancer.

The objective was to investigate how prostate cancer and its treatment affects sexual, urinary and bowel functions and to what extent eventual complications cause distress. A questionnaire was sent to 431 men aged 50-80 years with prostate cancer diagnosed in 1992 in the Stockholm area (Sweden) and 435 randomly selected men with a similar age distribution. Sexual function, as compared with their youth, was diminished in a majority of all men.

Deferred treatment for clinically localized prostate cancer.

With the available data, deferred treatment is definitely an option for patients with low grade clinically localized prostate cancer if their life expectancy is 10 years or less and avoids the side-effects of treatment. Many patients will avoid the need for therapy of their prostate cancer during their remaining lifetime.

Distinguishing prognostic and treatment-predictive information for localized prostate cancer.

Objectives: To distinguish the concepts of prognostic and treatment-predictive information for localized prostate cancer.

Methods: We defined a prognostic factor as one that identifies subgroups associated with differing outcomes in untreated patients. A treatment-predictive factor identifies patients with differing outcomes as a consequence of treatment and is best identified in a large, randomized trial.

Modulation of smooth muscle activity by nitric oxide in the human upper urinary tract.

The aim of the study was to ascertain whether nitric oxide (NO) might regulate motility in the human upper urinary tract. Smooth muscle activity in the human renal pelvis and proximal ureter was studied in vitro in organ baths, and nitric oxide synthase (NOS) activity was studied by measurement of citrulline formation. NO, glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) significantly reduced the frequency of spontaneous rhythmic contractions in renal pelvis and proximal ureter.

Radical prostatectomy, radiotherapy or deferred treatment for localized prostate cancer?

Before considering the possible biases discussed above, the results as reported in the current literature may indicate an advantage for radical prostatectomy in disease specific survival at 10 years' follow-up when compared with external radiation therapy and deferred treatment. It appears that most of the obvious biases found in the literature work in favour of radical prostatectomy. The actual advantage of radical prostatectomy with respect to disease specific survival at 10 years may therefore be less than the data complications suggest.

Localization of nitric oxide synthase activity in the human lower urinary tract and its correlation with neuroeffector responses.

Objectives: The present study was designed to correlate the localization of nitric oxide synthase (NOS) activity to nerve-induced smooth muscle responses in the human lower urinary tract.

Methods: Nerve-induced smooth muscle activity was studied in the human lower urogenital tract. NOS activity was studied by measurement of citrulline formation and guanylate cyclase activity.

Deferred treatment of clinically localized low grade prostate cancer: the experience from a prospective series at the Karolinska Hospital.

From 1978 to 1982, 172 patients with stages T1 to 3NxM0 prostate cancer were included in a surveillance protocol with deferred treatment on symptomatic progression. Median patient age at diagnosis was 68 years (range 38 to 89 years). Mean followup was 80 +/- 32 months.

Prognostic value of deoxyribonucleic acid content in prostate cancer: a review of current results.

A total of 115 articles on prostate cancer were reviewed for data on the prognostic value of DNA content in the tumor cells. In 44 series, data pertinent to this review were found. There was no consensus in the literature with respect to methods of analysis of DNA content or definitions of subclasses of DNA content such as categories of ploidy.

Results of conservative management of clinically localized prostate cancer.

Background: The selection of treatment for patients with localized prostate cancer requires reliable information about the outcome of conservative management. Previous studies of this question are generally considered unreliable because they were uncontrolled and nonrandomized.

Methods: We performed a pooled analysis of 828 case records from six nonrandomized studies, published since 1985, of men treated conservatively (with observation and delayed hormone therapy but no radical surgery or irradiation) for clinically localized prostate cancer.

Iodine-125 brachytherapy for clinically localized prostate cancer: a 5-year follow-up of outcome and complications.

Thirty-seven patients with clinically localized prostate cancer of all grades were treated by suprapubic digitally guided implantation of 125I seeds. The median age at the time of diagnosis was 68 years. The mean follow-up period was 62 +/- 19 months.

Nitric oxide synthase activity in the human urogenital tract.

Nitric oxide (NO) has been suggested as a nonadrenergic non-cholinergic neurotransmitter in the urogenital tract and has previously been shown to have a smooth muscle relaxing effect in the urogenital organs both in various animals and in humans. It has been shown that NO is a mediator of the erection and the dilatation of the bladder neck and urethra. The aim of the study was to analyse nitric oxide synthase (NOS) activity in the human urogenital tract.

The TNM system of 1992. Comments from the TNM working group. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

The TNM working group acknowledges the multinational agreement reached in the 1992 TNM classification, but nevertheless gives some suggestions for modifications. The main interest of the group has been to evaluate parameters suitable for further ramification of the system. The group found that parameters such as DNA ploidy, PSA, nuclear roundness factor, are not yet ready for this purpose.

Recent results of management of palpable clinically localized prostate cancer.

Background: There is uncertainty regarding if, when, and how localized prostate cancer should be managed.

Methods: To examine evidence of a beneficial effect of aggressive treatment on metastatic failure and disease-specific mortality in clinically localized prostate cancer, the authors compiled data from the literature since 1980 regarding radical prostatectomy, external radiation therapy, and deferred treatment.

Results: The weighted mean of reported disease-specific survival at 10 years was 93% for radical prostatectomy, 83% for deferred treatment, and 74% for external radiation therapy.

Deferred treatment of low grade stage T3 prostate cancer without distant metastases.

Fifty patients with extracapsular prostate cancer without known distant metastases were included in a protocol of surveillance followed by deferred treatment of progression. The median observed followup time was 78 months. The risk of developing distant metastases, if not dying before, was 24% and 37% at 5 and 9 years, respectively.

Conservative management of localized prostatic cancer.

Radical prostatectomy (RP), irradiation (RT), early endocrine therapy (EET), and expectant treatment (DT) are strategies for the management of clinically localized prostatic cancer. EET has not been systematically studied, but warrants prospective exploration. DT in uncontrolled studies results in disease-specific survival rates at 10 years that appear comparable to those achieved following RP or RT and may be considered a management option in patients with limited life expectancy.