Secretions from seminal vesicles lack characteristic markers for prostasomes.

BACKGROUND: Prostasomes are suggested to be produced in the prostate gland. Although biochemical studies support this, some immunohistochemical findings indicate that also the seminal vesicles could be a source of prostasomes. Therefore, we have compared the secretion of the vesicles with that of the prostate using biochemical and ultrastructural techniques. METHODS: Ultracentrifuged pellets of substance from seminal vesicle secretions were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and flow cytometry. The secretory cells of the seminal vesicles were examined with transmission electron microscopy. These findings were then compared with published results from similar studies of the prostate secretory cells. RESULTS: In SDS-PAGE, the seminal vesicle pellets lacked the three prostasome-characteristic CD-markers, namely CD10, CD13, and CD26, but expressed two proteins of about 55 kDa and 70 kDa, corresponding to clusterin and heat shock protein (HSP70). Flow cytometry showed the presence of secretion particles in the seminal pellet, although of a smaller size than that of the prostasomes. Electron microscopy of the luminal part of the cells in the seminal vesicles demonstrated many secretion granules, each enclosed in a vesicle with a size of about 1 microm. CONCLUSIONS: Pelleted seminal vesicle secretion is different to prostate secretion in several ways. No prostasome characteristics were detected in the pelleted seminal vesicle secretion.

Experiences of randomization: interviews with patients and clinicians in the SPCG-IV trial.

OBJECTIVE: Recruitment of both patients and clinicians to randomized trials is difficult. Low participation carries the risk of terminating studies early and making them invalid owing to insufficient statistical power. This study investigated patients' and clinicians' experiences of randomization with the aim of facilitating trial participation in the future. MATERIAL AND METHODS: This was a qualitative study using content analysis. Patients offered to participate in a randomized trial and randomizing clinicians were interviewed. Five participants, four non-participants and five randomizing clinicians were interviewed, 2-8 years from randomization. RESULTS: Clinicians used strategies in interaction with the patients to facilitate decision making. Patients' attitudes differed and experiences of relatives or friends were often stated as reasons for treatment preferences. Patients described that letting chance decide treatment was a difficult barrier to overcome for randomization. The clinicians used a number of different strategies perceived to make randomization more acceptable to their patients. The clinicians' own motivation for randomizing patients for trials depended on the medical relevance of the study question and the clinicians' major obstacle was to maintain equipoise over time. Regular meetings with the study group helped to maintain equipoise and motivation. CONCLUSIONS: To establish a good platform for randomization the clinician needs to know about the patient's treatment preferences and the patient's attitude concerning the role of the clinician to facilitate decision making. The strategies used by the clinicians were perceived as helpful and could be tested in an intervention study.

Prognostic markers under watchful waiting and radical prostatectomy.

A suitable setting to analyze factors that determine prognosis or treatment response in prostate cancer is an unbiased comparison of radical prostatectomy and watchful waiting as in the Scandinavian Prostate Cancer Group Trial number 4. In our previous presentation of 10-year results, we studied Gleason score, serum prostate-specific antigen (PSA) at diagnosis, and age at diagnosis as modifiers of the effect of radical prostatectomy on survival. Because overall prognostic information obtained by these parameters or by tumor stage was not provided in our publication, we now present these data in the two study arms separately.

Prediction of the volume of large prostate cancers by multiple core biopsies.

OBJECTIVE: To evaluate whether large-volume prostate cancers can be predicted by means of multiple needle biopsies. MATERIAL AND METHODS: In 115 men, 8-14 (mean 10) biopsies were taken, including eight from standardized positions (apex, mid-medial, mid-lateral and base). Biopsies were reviewed, the length of the cancer measured and the percentage cancer length calculated. All men underwent radical prostatectomy. The prostatectomy specimens were totally embedded and the tumor volume was measured planimetrically. The predictive values of the number and percentage of cores positive for cancer, cancer length and percentage cancer length were calculated for tumor volumes of >4, >6 and >8 ml. RESULTS: Using univariate logistic regression, cancer length and percentage cancer length predicted tumor volumes of >4 (p<0.001), >6 (p<0.001) and >8 ml (p<0.05). These measures were better predictors of tumor volume than the number and percentage of cores positive for cancer. A biopsy cancer length of > or =30 mm and a percentage cancer length of > or =25% predicted a tumor volume of >4 ml in 95% and 93% of cases, respectively. For tumor volumes of >6 or >8 ml, predictive values were lower. Tumor volumes of <2 and <4 ml were found in 13% and 35%, respectively of men with as many as six positive cores, indicating that the number of positive cores was less useful as a predictor of tumor volume than the cancer length. CONCLUSIONS: Cancer length and percentage cancer length are significant predictors of large tumor volumes. It is recommended that the linear extent of cancer in prostate biopsies should be reported by the pathologist.

Radical prostatectomy versus watchful waiting in early prostate cancer.

BACKGROUND: In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results. METHODS: From October 1989 through February 1999, 695 men with early prostate cancer (mean age, 64.7 years) were randomly assigned to radical prostatectomy (347 men) or watchful waiting (348 men). The follow-up was complete through 2003, with blinded evaluation of the causes of death. The primary end point was death due to prostate cancer; the secondary end points were death from any cause, metastasis, and local progression. RESULTS: During a median of 8.2 years of follow-up, 83 men in the surgery group and 106 men in the watchful-waiting group died (P=0.04). In 30 of the 347 men assigned to surgery (8.6 percent) and 50 of the 348 men assigned to watchful waiting (14.4 percent), death was due to prostate cancer. The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years, for a relative risk of 0.56 (95 percent confidence interval, 0.36 to 0.88; P=0.01 by Gray's test). For distant metastasis, the corresponding increase was from 1.7 to 10.2 percentage points, for a relative risk in the surgery group of 0.60 (95 percent confidence interval, 0.42 to 0.86; P=0.004 by Gray's test), and for local progression, the increase was from 19.1 to 25.1 percentage points, for a relative risk of 0.33 (95 percent confidence interval, 0.25 to 0.44; P<0.001 by Gray's test). CONCLUSIONS: Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial.

Prostasomes are secreted from poorly differentiated cells of prostate cancer metastases.

BACKGROUND: Prostasomes are small (40-500 nm), granule-like bodies, found in normal epithelial cells of the prostate and secreted into the prostate duct system. Also poorly differentiated prostate cancer cells are producing prostasomes, since we could isolate and purify prostasomes from vertebral metastases with biochemical methods. To find out whether these prostasomes are secreted into extracellular sites of the metastases, we used electron microscopy. METHODS: Small biopsies from vertebral metastases of prostate cancer, taken directly from the operating field at surgery, were immediately fixated, embedded in plastic and processed for electron microscopy. RESULTS: We found that prostasomes could be identified extracellularly in the interstitial tissues as well as in the cytoplasm of the metastatic cells. CONCLUSION: We conclude that prostasomes produced by the cells of vertebral metastases of prostate cancer are distributed both intracellularly and extracellularly in the interstitial spaces of the tissue. Thus, prostasomes of metastases could perhaps be exploited as targets for immunodiagnosis and/or immunotherapy.

A systematic overview of radiation therapy effects in prostate cancer.

A systematic review of radiation therapy trials in prostate cancer has been performed according to principles adopted by the Swedish Council of Technology Assessment in Health Care (SBU). This synthesis of the literature is based on data from one meta-analysis, 30 randomized trials, many dealing with hormonal therapy, 55 prospective trials, and 210 retrospective studies. Totally the studies included 152,614 patients. There is a lack of properly controlled clinical trials in most important aspects of radiation therapy in prostate cancer. The conclusions reached can be summarized as follows: * There are no randomized studies that compare the outcome of surgery (radical prostatectomy) with either external beam radiotherapy or brachytherapy for patients with clinically localized low-risk prostate cancer. However, with the advent of widely accepted prognostic markers for prostate cancer (pre-treatment PSA, Gleason score, and T-stage), such comparisons have been made possible. There is substantial documentation from large single-institutional and multi-institutional series on patients with this disease category (PSA < 10, GS < or = 6, < or = T2b) showing that the outcome of external beam radiotherapy and brachytherapy is similar to those of surgery. * There is fairly strong evidence that patients with localized, intermediate risk, and high risk (pre-treatment PSA > or = 10 and/or GS > or = 7 and/or > T2) disease, i.e. patients normally not suited for surgery, benefit from higher than conventional total dose. No overall survival benefit has yet been shown. * Dose escalation to patients with intermediate-risk or high-risk disease can be performed with 3D conformal radiotherapy (photon or proton) boost, with Ir-192 high dose rate brachytherapy boost, or brachytherapy boost with permanent seed implantation. Despite an increased risk of urinary tract and/or rectal side effects, dose-escalated therapy can generally be safely delivered with all three techniques. * There is some evidence that 3D conformal radiotherapy results in reduced late rectal toxicity and acute anal toxicity compared with radiotherapy administered with non-conformal treatment volumes. * There is some evidence that postoperative external beam radiotherapy after radical prostatectomy in patients with pT3 disease prolongs biochemical disease-free survival and that the likelihood of achieving long-term DFS is higher when treatment is given in an adjuvant rather than a salvage setting. A breakpoint seems to exist around a PSA level of 1.0 ng/mL, above which the likelihood for eradication of the recurrence of cancer diminishes. * After prostatectomy, endocrine therapy prior to and during adjuvant radiotherapy may result in longer biochemical disease-free survival than if only adjuvant radiotherapy is given. No impact on overall survival has been shown. * There is fairly strong evidence that short-term endocrine therapy prior to and during radiotherapy results in increased disease-free survival, increased local control, reduced incidence of distant metastases, and reduced cause-specific mortality in patients with locally advanced disease. * There is some evidence that short-term endocrine therapy prior to and during radiotherapy results in increased overall survival in a subset (GS 2-6) of patients with locally advanced disease. * There is strong evidence that adjuvant endocrine treatment after curative radiotherapy results in improved local control, increased freedom from distant metastases, and increased disease-free survival in patients with loco-regionally advanced and/or high-risk disease. * There is moderately strong evidence that adjuvant endocrine treatment after radiotherapy results in longer overall survival compared with radiotherapy alone in patients with loco-regionally advanced disease.

Ultrastructure of the secretion of prostasomes from benign and malignant epithelial cells in the prostate.

BACKGROUND: Prostate epithelial cells are producing, among other things, a fluid secretion containing small bodies, the prostasomes. The mechanism of synthesis of the prostasomes is not known in details, neither is it known whether the mode of prostasome production changes at a neoplastic transformation of the prostate cells. Due to the small size of the prostasomes, we have used electron microscopy for evaluating the production and distribution of prostasomes in benign and neoplastic cells of the prostate. METHODS: Benign and neoplastic areas in plastic embedded core biopsy specimens of prostate tissue were identified, and secreting cells were selected. The corresponding areas on the plastic blocks were further processed for examination in the electron microscope. RESULTS: The electron microscopical examination showed that the secretory machinery was similar in both types of tissue. Thus, in both benign and well-differentiated neoplastic cells studied, the formation of storage vesicles in the Golgi areas was similar, the content of the vesicles appeared similar, the structure and distribution of prostasomes were alike, and in both benign and malignant tissue, the secretion in the gland ducts showed the same appearance with many prostasomes. CONCLUSION: We conclude that cells in benign prostate tissue and cells in well-differentiated prostate carcinoma show great similarities in synthesis, storage, and release of prostasomes. However, this does not exclude the presence of other changes, for instance biochemical ones, in the prostasomes.

A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer.

BACKGROUND: Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. METHODS: From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression. RESULTS: During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96). CONCLUSIONS: In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.

Quality of life after radical prostatectomy or watchful waiting.

BACKGROUND: We evaluated symptoms and self-assessments of quality of life in men with localized prostate cancer who participated in a randomized comparison between radical prostatectomy and watchful waiting. METHODS: Between 1989 and 1999, a group of Swedish urologists randomly assigned men with localized prostate cancer to radical prostatectomy or watchful waiting. In this follow-up study, we obtained information from 326 of 376 eligible men (87 percent) concerning certain symptoms, symptom-induced distress, well-being, and the subjective assessment of quality of life by means of a mailed questionnaire. RESULTS: Erectile dysfunction (80 percent vs. 45 percent) and urinary leakage (49 percent vs. 21 percent) were more common after radical prostatectomy, whereas urinary obstruction (e.g., 28 percent vs. 44 percent for weak urinary stream) was less common. Bowel function, the prevalence of anxiety, the prevalence of depression, well-being, and the subjective quality of life were similar in the two groups. CONCLUSIONS: The assignment of patients to watchful waiting or radical prostatectomy entails different risks of erectile dysfunction, urinary leakage, and urinary obstruction, but on average, the choice has little if any influence on well-being or the subjective quality of life after a mean follow-up of four years.