Background The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.

Methods The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [³H]-thymidine and [³⁵S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP.

Results LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC₅₀ values of 3 and 10 μM, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC₅₀  = 2.5, and 0.35 μM, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra^®) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.

Conclusions The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH.

We study the G972R polymorphism in the Insulin receptor substrate 1 gene (IRS1) and the +1127 PstI polymorphism of the Insulin gene (INS), in 120 and 151, respectively, incidentally discovered, histologically verified prostate cancers, and in 185 healthy control subjects. The number of IRS1 R allele was found to be significantly associated with increased risk of prostate cancer. Analysis of the INS +1127 PstI polymorphism shows no significant differences between cases and controls. We conclude that subjects carrying one or two R-alleles at the IRS1 G972R polymorphic site are at an elevated risk of developing prostate cancer.

We study the CAG repeat region in exon 1 of the androgen receptor (AR) and the TaqI polymorphism in exon 9 of the vitamin D receptor (VDR) and the association with prostate cancer. 137 incidentally discovered, histologically verified prostate cancers were analysed for CAG repeat length in AR and genotype at the TaqI site of the VDR. 124 control subjects were analysed to determine the CAG repeat length and TaqI genotype determined for 176 control subjects. An unpaired t-test shows that the mean CAG repeat length was significantly (p < 0.001) shorter among cases (20.1 repeats) compared with controls (22.5 repeats). Dividing the prostate cohort and controls into tertiles (19, 20–22, 23 repeats) shows that short repeats are significantly more common among cases (odds ratio (OR) 4.45, p = 0.00003). Genotype frequencies for the TaqI polymorphism reveals no significant differences between cases and controls. We conclude that men with a short CAG repeat in the androgen receptor gene have an increased risk of developing prostate cancer.

Background: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up. Methods: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided. Results: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P =. 09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94, P =. 03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88, P =. 006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8, P <. 001). Conclusion: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. © The Author 2008. Published by Oxford University Press.

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. Copyright © 2005 Massachusetts Medical Society.

BACKGROUND In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. METHODS From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. RESULTS During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment.

Objective. The incidence of prostate cancer in Sweden is increasing rapidly, as is treatment with curative intent. Radical prostatectomy (RP) is currently commonly performed, either within or outside large high-volume centres. The aim of this study was to assess the 30-day mortality rate after RP in Sweden. Material and methods. In this nationwide population-based study, all men diagnosed with localized prostate cancer (andlt;= 70 years, clinical stadium T1-2, prostate-specific antigen andlt;20 ng/ml) who underwent RP in Sweden between 1997 and 2002 were identified through the National Prostate Cancer Register (NPCR). Mortality within 30 days of RP was analysed through linkage between the follow-up study of the NPCR and the Regional Population Registers. The cause of death in the death certificates were compared with data from the hospitals concerned. To validate the results, a record linkage between the Inpatient Register and the National Population Register was also performed. Results. The number of RPs performed increased over time. Among 3700 RPs performed, four deaths occurred during the first 30 days, yielding a 0.11% 30-day mortality rate. These deaths occurred at three different types of hospital and were all probably related to the RP. Conclusion. This study provides further evidence that RP is a procedure with very low perioperative mortality even when performed outside high-volume centres.

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Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. less thanbrgreater than less thanbrgreater thanMethods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. less thanbrgreater than less thanbrgreater thanResults: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). less thanbrgreater than less thanbrgreater thanConclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. less thanbrgreater than less thanbrgreater thanImpact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease.

Objective. To evaluate the reliability of cause-of-death diagnoses among prostate cancer patients. Material and methods. Information from death certificates obtained from the Swedish Death Register was compared with systematically reviewed medical records from the population-based Swedish Regional Prostate Cancer Register, South-East Region. In total, 5675 patients were included who had been diagnosed with prostate cancer between 1987 and 1999 and who had died before 1 January 2003. Results. The proportion of prostate cancer cases classified as having died from prostate cancer was 3% higher in the official death certificates than in the reviewed records [0.03, 95% confidence interval (CI) 0.02 to 0.04]. Overall agreement between the official cause of death and the reviewed data was 86% (95% CI 85 to 87%). A higher accuracy was observed among men with localized disease (88%, 95% CI 87 to 89%), aged 60 years or younger at death (96%, 95% CI 93 to 100%), or who had undergone curative treatment (91%, 95% CI 88 to 95%). This study indicates a relatively high reliability of official cause-of-death statistics of prostate cancer patients in Sweden. Conclusion. Mortality data obtained from death certificates may be useful in the evaluation of large-scale prostate cancer intervention programmes, especially among younger patients with localized disease. © 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS).

Objective. To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP, Estradurin®) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. Material and methods. In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240mg i.m. twice a month for 2months and thereafter monthly, or flutamide (Eulexin®) 250mg t.i.d. per os in combination with either triptorelin (Decapeptyl®) 3.75mg i.m. per month or on an optional basis bilateral orchidectomy. Results. At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). Conclusions. PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis. © 2008 Taylor & Francis.

Objective. This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin (R)) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease. Material and methods. Nine-hundred and fifteen patients with T0-4, Nx, M1, G1-3, hormone- naive prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin (R)) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl (R)) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression. Results. There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p andlt; 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036). Conclusions. Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e. g. avoidance of osteopenia and hot flushes and the low price, are given priority.

Objective: The influence of specific symptoms on emotions and social activities in the individual patient vanes. Little is known about this variation in urinary bladder cancer survivors (in other words, about the relative importance of sources of symptom-induced distress). Methods: We attempted to enrol 404 surgical patients treated with cystectomy and a conduit or reservoir in four Swedish towns (Stockholm, Orebro, Jonkoping, Linkoping), 101 surgical patients treated with cystectomy and orthotopic neobladder at the Herlev Hospital in Copenhagen, Denmark, and 71 patients treated with radical radiotherapy for bladder cancer, as well as 581 men and women controls in Stockholm and Copenhagen. An anonymous postal questionnaire was used to collect the information. Results: A total of 503 out of 576 (87%) treated patients and 422 out of 581 (73%) controls participated but 59 patients were excluded. The primary source of self-assessed distress among cystectomised patients was compromised sexual function, reduced intercourse frequency caused great distress in 19% of the conduit patients, 20% of the reservoir patients and 19% of the bladder substitute patients. The primary source of self-assessed distress in patients treated with radical radiotherapy was symptoms from the bowel, 17% reported great distress due to diarrhoea, 16% due to abdominal pain, 14% due to defecation urgency and 14% due to faecal leakage. The highest proportion of subjects being distressed was 93% (substantial: 43%, moderate: 29% and little: 21%) for treated upper or lower urinary retention (indwelling catheter or nephrostomy). Conclusion: The distress caused by a specific symptom varies considerably and the prevalence of symptoms causing great distress differs between treatments in bladder cancer survivors. It is possible that patient care and clinical research can be made more effective by focusing on important sources of symptom-induced distress. (C) 2003 Elsevier Science B.V. All rights reserved.

Objective. To investigate the type of urinary diversion performed after cystectomy in patients with muscle-invasive bladder cancer in Sweden, using data from a population-based national register. Material and methods. Since 1997, the Swedish Bladder Cancer Register has included more than 90% of all patients with newly diagnosed bladder cancer. The different types of urinary diversion performed in 1997-2003 were analysed, comparing non-continent diversion (ileal conduit) with continent reconstruction (bladder substitution or continent cutaneous diversion). Results. During the study period, 3463 patients were registered with clinical T2-T4 non-metastatic bladder cancer. Cystectomy was performed in 1141 patients with ileal conduit in 732 (64%) and continent reconstruction in 409 (36%). Ileal conduit was used more frequently in females than males (p = 0.019), in patients older than 75 years (p andlt; 0.00001), and in those with less favourable TNM classification. Continent reconstruction was done more often at university hospitals than at county hospitals (p andlt; 0.00001), but rarely in the northern and western healthcare regions compared with other regions (p andlt; 0.00001). Nationwide, the proportion of registered continent reconstructions decreased, although the absolute number was relatively stable (50-60 per year). Conclusions. Continent reconstruction after cystectomy for muscle-invasive bladder cancer is performed more often in some healthcare regions and in patients at university hospitals than in county hospitals, indicating a substantial provider influence on the choice of urinary diversion. Over time, the proportion of these procedures has decreased, while the absolute number has remained low and stable; therefore, concentration in high-volume hospitals specialized in bladder cancer and continent reconstruction seems appropriate.

Aims: To evaluate different aspects of recurrence and, when appropriate, progression in primary Ta/T1 urinary bladder cancer.

Patients and methods: All evaluable patients diagnosed with primary Ta/T1 urinary bladder cancer in Linköping and Norrköping between 1992 and 2007 were included prospectively in the study cohort. Histopathology results were classified according to the TNM system and were reviewed by a reference pathologist using the WHO 1999 criteria (except in the studies reported in Papers I and IV). Risk factors for local recurrence were evaluated using data from the period 1992–2001 (Paper I). Tumour size (Paper II) and bladder wash cytology (Paper III) at primary diagnosis were assessed regarding the impact on recurrence and progression, and tumour presence in the marginal resection in primary and recurrent Ta/T1 bladder cancer was investigated considering effects on recurrence in patients treated between 2001 and 2010 (Paper IV). Furthermore, surgical experience measured as training status (resident or specialist) and surgical volume (both during the study period and lifetime) were analysed regarding their influence on recurrence and progression (Paper V).

Results: Tumour size > 30 mm (p < 0.001) and multiplicity (p = 0.021) were significantly associated with local recurrence (Paper I). Tumour sizes 16–30 mm and > 30 mm were correlated with recurrence (p = 0.003 and p < 0.001, respectively) but not with progression (Paper II). High-grade malignant bladder wash cytology proved to be predictive of both recurrence (p < 0.001) and progression (p = 0.036) as was shown in Paper III. A tumour-positive marginal resection was related to overall (p < 0.001) and local (p < 0.001) recurrence (Paper IV). Transurethral resection of bladder tumours performed by residents was associated with recurrence (p = 0.004) but not with progression. No differences in relation to either recurrence or progression were found for the surgical volume approach at the chosen cut-offs (Paper V).

Conclusions: The present studies identified new risk factors for recurrence (tumours > 15 mm, high-grade bladder wash cytology at diagnosis, tumour-positive marginal resection, and surgery performed by residents) and progression (local recurrence and high-grade malignant bladder wash cytology at diagnosis), which in the future may be integrated into follow-up schedules or risk profiles for patients with Ta/T1 urinary bladder cancer.

Objective To describe characteristics and quality-of-life (QoL), and to define factors associated with long-term survival in a subgroup of patients with prostate cancer with M1b disease. Patients and Methods The study was based on 915 patients from a prospective randomised multicentre trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Long-term survival was defined as patients having an overall survival of &gt;= 10 years, and logistic regression models were constructed to identity clinical predictors of survival. QoL during follow-up was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - C30 version 1 (EORTC-C30) ratings. Results In all, 40 (4.4%) of the 915 men survived for &gt;10 years. Factors significantly associated with increased likelihood of surviving for &gt;10 years in the univariate analyses were: absence of cancer-related pain; Eastern Cooperative Oncology Group (ECOG) performance status of &lt;2; negligible analgesic consumption; T-category of 1-2; prostate-specific antigen (PSA) level of &lt;231 mu g/L; and a Soloway score of 1. In the multivariate analyses, ECOG performance status of &lt;2, PSA level of &lt;231 mu g/L, and Soloway score of 1, were all independent predictors of long-term survival. All subscales of the EORTC-C30 were higher in this group than for patients with short survival, but slowly declined over the decade. Conclusion A subgroup of patients with prostate cancer with M1b disease and certain characteristics showed a positive long-term response to androgen-deprivation therapy with an acceptable QoL over a decade or more. Independent predictors of long-term survival were identified as ECOG performance status of &lt;2, limited extent of bone metastases (Soloway score of 1), and a PSA level of &lt;231 mu g/L at the time of enrolment.

OBJECTIVE To identify prognostic factors, and to estimate the long-term disease-specific and annual disease-specific mortality rates of low-risk prostate cancer patients from the early prostate-specific antigen (PSA) era. PATIENTS AND METHODS We studied data extracted from the Southeast Region Prostate Cancer Register in Sweden, on 1300 patients with clinically localized low-risk tumors, T1-2, PSA level amp;lt;= 10 mu g/L and Gleason scores 2-6 or World Health Organization Grade 1, diagnosed 1992-2003. The Cox multivariate regression model was used to evaluate factors predicting survival. Prostate cancer death rates per 1000 person-years were estimated for 4 consecutive follow-up time periods: 0-5, 5-10, 10-15, and 15+ years after diagnosis. RESULTS During the follow-up of overall survivors (mean 10.6 years; maximum 21.8 years), 93 patients (7%) died of prostate cancer. Cancer-specific survival was 0.98 (95% confidence interval [CI] 0.97-0.99), 0.95 (95% CI 0.93-0.96), 0.89 (95% CI 0.86-0.91), and 0.84 (95% CI 0.80-0.88), 5, 10, 15, and 20 years after diagnosis. The 5-year increases in cancer-specific mortality were statistically significant (P amp;lt;. 001). Patients with PSA amp;gt;= 4 mu g/L managed initially with watchful waiting and those aged 70 years or older had a significantly higher risk of dying from their prostate cancer. CONCLUSION The long-term disease-specific mortality of low-risk localized prostate cancer is low, but the annual mortality rate from prostate cancer gradually increases. This indicates that some tumors slowly develop into lethal cancer, particularly in patients 70 years or older with a PSA level amp;gt;= 4 mu g/L. (C) 2016 Elsevier Inc.

Objective: The aim of this study was to investigate the impact of bone metastasis on survival and quality of life (QoL) in men with hormone-naive prostate cancer. Materials and methods: The study included 900 patients from a randomized trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Extent of bone metastasis was categorized according to a modified Soloway score: score 1, n=319; score 2, n = 483; and score 3, n = 98 patients. The primary outcome measurements were mean differences in QoL and overall survival. Results: QoL rating scales showed a decrease with increasing extent of bone metastasis (p amp;lt; 0.001). The mean global health status decreased from 64.4 to 50.5 for Soloway score 1 and 3, respectively. Following adjustment for performance status, analgesic consumption, grade of malignancy, alkaline phosphatase, prostate-specific antigen, haemoglobin and global health status, Soloway score 2 and 3 had a 47% [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.21-1.80] and 78% (HR 1.78 95%, CI 1.32-2.42) increased mortality, respectively, compared to Soloway score 1. Independent predictive factors of mortality were assessed. Conclusions: Patient grouping based on three categories of extent of bone metastasis related to performance status, haemoglobin and global health status at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.

Objective less thanbrgreater than less thanbrgreater thanTo investigate the influence of curative treatment on cause-specific mortality in men diagnosed with prostate cancer (PCa) with serum prostate-specific antigen (PSA) levels between 20 and 100 ng/mL. less thanbrgreater than less thanbrgreater thanMaterials and Methods less thanbrgreater than less thanbrgreater thanPatients with PCa (T1-4, N0/N1/NX, M0/MX), PSA 20-100 ng/mL and age andlt;= 75 years were identified in the National Prostate Cancer Register of Sweden. less thanbrgreater than less thanbrgreater thanData on co-morbidity diagnoses were obtained from the National Patient Register and cause of death from the Cause of Death Register. less thanbrgreater than less thanbrgreater thanFollowing adjustment for age at diagnosis, co-morbidity burden, Gleason score, T-category, PSA level and cause-specific mortality in relation to treatment were estimated using Cox regression analysis. less thanbrgreater than less thanbrgreater thanResult less thanbrgreater than less thanbrgreater thanA total of 11 380 men were diagnosed with PCa between 1996 and 2008 and fulfilled the inclusion criteria. less thanbrgreater than less thanbrgreater thanThe cumulative 10-year PCa-specific mortality was 36% for patients receiving only palliative treatment and 13% for those treated with curative intent. less thanbrgreater than less thanbrgreater thanFor the 8462 (74%) patients with PSA levels from 20 to 50 ng/mL at diagnosis, the hazard ratio for death from PCa was 0.23 (95% confidence interval 0.19-0.27) for those treated with curative intent compared with those given palliative treatment after adjusting for age, co-morbidity, T category, PSA level and Gleason score. The corresponding hazard ratio was 0.22 (95% confidence interval 0.17-0.30) for patients with PSA levels from 51 to 100 ng/mL. less thanbrgreater than less thanbrgreater thanConclusion less thanbrgreater than less thanbrgreater thanTreatment with curative intent for men with high-risk PCa was associated with reduced cause-specific mortality and should be considered even when serum PSA exceeds 20 ng/mL. Keywords prostate cancer, prostate-specific antigen, high-risk tumours, curative treatment, palliative treatment, population-based study

Background: There is insufficient information regarding the benefit of treatment with curative intent for men with localised poorly differentiated prostate cancer (PCa). Objective: To evaluate relative survival in men with potentially curable PCa in relation to Gleason score (GS) and treatment as practiced in the community at large. Design, setting, and participants: A population-based study including all men with localised PCa registered in Swedens National Prostate Cancer Register. Interventions: Hormonal therapy, watchful waiting, and treatment with curative intent. Measurements: The ratio of observed deaths to expected deaths, determined from survival in the general male population of the same age, was assessed using Poisson regression analysis, with GS and treatment as covariates. Interaction between GS and treatment was tested in a multivariate Cox proportional hazard analysis. Results and limitations: A total of 31 903 men with potentially curable tumour (T1-T3, N0/NX, M0/MX, age andlt; 75 yr, and prostate-specific antigen [PSA] andlt; 20 ng/ml) were identified. GS was recorded for 28 454 of these men. Some 19 606 men (60.8%) were treated with curative intent, and 12 645 men (39.2%) were given either hormonal treatment or expectant management. The ratios between observed and expected survival gradually increased for men with GS 10, with GS to 3.3 for men treated conservatively and to 1.4 for men treated with curative intent. There was a significant interaction between GS and treatment, with a relatively greater benefit from treatment with curative intent for men with high-grade tumours. The results have to be interpreted with some caution, as there was no randomisation between the treatment groups. Conclusions: Survival for men with well-differentiated tumours is close to that of the general population, regardless of treatment, but the outcome is dismal for men with poorly differentiated tumours, whichever treatment is applied. Nevertheless, men with poorly differentiated tumours benefit more from curative treatment than do men with well-differentiated tumours.

Abstract Objective. To determine whether there are differences in the quantity and quality of sleep, including sleep efficiency and insomnia, and health-related quality of life (HRQoL) between patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO), men from the general population and patients with inguinal hernia. Material and methods. The designs were descriptive and comparative. The groups consisted of 239 patients aged 45-80 years who were referred to urological departments with LUTS suggestive of benign prostatic obstruction. The comparison groups consisted of 213 randomly selected men from the general population, stratified according to age and geographical region, and 200 patients with inguinal hernia. The setting was one university and two general hospitals. The method was self-administered questionnaires about demography, comorbidity, sleep and health-related quality of life. Further, patients with LUTS answered questions about urinary symptoms and disease-specific quality of life. Results. The prevalence of insomnia was 40%, 26% and 19% and the prevalence of sleep efficiency < 85% was 49%, 38.5% and 31% in the LUTS, general population and hernia groups, respectively. The median number of nocturnal micturitions was 2, 1 and 1. In the LUTS group (n = 216), 47% had IPSS 8-19 and 44% had >/= 20 points. The HRQoL was significantly impaired in patients with LUTS compared with one or both of the comparison groups (p values < 0.05). Conclusions. Patients with LUTS suggestive of BPO had significantly impaired sleep, a higher prevalence of insomnia and significantly impaired HRQoL compared with one or both of the comparison groups.

Aims: The overall aim was to determine how lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) affect sleep, health related quality of life and disease specific quality of life, and how the men’s urinary symptoms affect their partners.

Subjects and methods: In papers I–II, a descriptive design with a pre-test and post-test was used and in papers III-IV the design was descriptive and comparative. The method was self-administered questionnaires. In papers I- II: The questionnaires were translated in the ethnographic mode. In paper I the reliability of the questionnaire was tested in 122 patients with LUTS/ BPO. The disease specific quality of life was studied before and after intervention in 572 consecutive patients with BPO, aged 45-94 yrs. In paper II, the partner specific quality of life was studied in partners to men with BPO before and after TURP. The reliability and the responsiveness of the questionnaire were tested in two groups with 51 partners each. Papers III-IV: A study of 239 men with LUTS, aged 45-80 yrs, and their partners (n=126) who were compared to randomly selected men from the population (n=213) and their partners (n=131). The men had an extra control group, men with inguinal hernia (n=200). Sleep and health related quality of life was studied in both men and their partners. The partners’ specific quality of life was also studied and the men with LUTS answered questions about urinary symptoms and disease specific quality of life.

Results: Papers I-II: All the tested questionnaires showed an acceptable reliability and responsiveness. I: Before and after intervention the prevalence of urinary incontinence was 46 % and 16 % respectively. II: Partners were affected by the patients’ BPO symptoms before and improved after the patients TURPs. III: Most sleep variables were significantly impaired in men with LUTS compared to one or both of the control groups. The men with LUTS had a significantly higher prevalence of insomnia (40 %) than both control groups and significantly lower sleep efficiency (49 %) than men with hernia. The men with LUTS were significantly impaired in most domains of the health related quality of life compared to men in the population. IV: There were no significant differences between the two partner groups regarding the quantity and quality of sleep or the health related quality of life.

Conclusions: All tested questionnaires showed an acceptable reliability and responsiveness.

The prevalence of urinary incontinence before and after intervention was higher than earlier reported.

Men with LUTS had significantly poorer sleep quality, reduced sleep efficiency and a higher prevalence of insomnia than men in the population and men with inguinal hernia.

The HRQOL is impaired in men with LUTS compared to men in the population and men with inguinal hernia.

Partners are affected by the patients’ symptoms, and it is emotional rather than practical aspects that affect them most.

Partners of men with LUTS did not differ significantly from partners in the population with regard to sleep and health related quality of life.

Objectives: Little is known about the quality of life experienced by the partners of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). The aims of this study were to translate a specific quality of life questionnaire for partners to patients with benign prostatic enlargement (BPE)/BPO to swedish and to test its reliability and responsiveness. A secondary aim was to evaluate the impact the patients' urinary symptoms have on their partners' specific quality of life.

Material and methods: This study was conducted using two groups: a reliability partner group; and a responsiveness/evaluation partner group. Both groups consisted of the partners of patients on the waiting list for transurethral resection of the prostate (TURP). The reliability of the quality of life questionnaire for the partners of men with BPE/BPO was tested in 51 partners, with a test-retest interval of 5 weeks. The partners' specific quality of life and the responsiveness of the questionnaire were evaluated in 51 partners by administering the questionnaire before and 3 months after the patient's TURP.

Results: At the test-retest, the Spearman's rank correlation coefficient for each question varied between 0.59 and 0.86 and Cronbach's was 0.80. Partners were affected by the patients' BPO symptoms. Compassion, worry about cancer and worry about an operation were the aspects of the specific quality of life that affected most partners (92%, 77% and 65%, respectively), whereas effects on spare time and household activities affected fewer partners: 35% and 24%, respectively. The specific quality of life among partners improved significantly after the patient's TURP.

Conclusions: The Swedish version of a partner-specific quality of life questionnaire for men with LUTS suggestive of BPE/BPO had an acceptable reliability and responsiveness. Partners are affected by the patients' symptoms, and it is emotional rather than practical aspects which most affect them.

Objectives: Firstly, to describe self-reported urinary symptoms and bothersomeness, including disease-specific quality of life (QOL), in patients with symptomatic benign prostatic obstruction (BPO) before and 6 months after intervention. Secondly, to identify factors which predict disease-specific QOL. Thirdly, to develop and test the reliability of an instrument to evaluate incontinence, the Linköping Incontinence Questionnaire (LIQ). Finally, to translate and test the reliability of Swedish versions of the International Prostate Symptom Score, including the bother question, the American Urological Association Symptom Problem Index (SPI) and the Benign Prostatic Hyperplasia Impact Index.

Material and methods: Disease-specific QOL was studied in 572/720 consecutively treated patients using structured questionnaires. The reliability of the instruments was tested in 122 patients with lower urinary tract symptoms (LUTS) or BPO.

Results: The frequency and weak stream items of the SPI were among those that best explained the patients' disease-specific QOL both before and after intervention. Before and after intervention the prevalence of urinary incontinence, assessed using the LIQ instrument, was 46% and 16%, respectively. Symptoms and disease-specific QOL improved most in the surgery group, intermediately in the transurethral incision of the prostate/transurethral microwave thermotherapy group and least in the drug therapy group.

Conclusions: The frequency and weak stream items of the SPI were the factors that best explained disease-specific QOL. The prevalence of incontinence before and after intervention was higher than that previously

Objective: To determine whether there are significant differences in sleep, partner specific and health related quality of life between partners of men with LUTS suggestive of benign prostatic obstruction (BPO) and partners of men from the population. Secondly, to identify factors related to the specific quality of life in partners of men with LUTS and the sleep efficiency.

Subjects and methods: The study designs were descriptive and comparative. The subjects were partners of men with LUTS suggestive of BPO (n=126) referred to departments of urology at one university and two general hospitals and partners (n=131) of randomly selected men from the general population. Self-administered questionnaires about demography, comorbidity, sleep, sexuality, partner specific and health related quality of life were used.

Results: Partners to men with LUTS suggestive of BPO were significantly more affected in all variables measuring partner specific quality of life compared to partners from the population. The most impaired aspects were compassion and worry about an operation or cancer.

In logistic regression, the only explanatory factors were having a partner belonging to the LUTS group for impaired partner specific quality of life and having a bed partner for high sleep efficiency.

There were no significant differences between the two groups regarding the quantity andquality of sleep or the health related quality of life.

Conclusions: The partner specific quality of life was impaired in partners of men with LUTS suggestive of BPO. Sleep and health related quality of life did not differ between partners of men with LUTS and partners in the population.

Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs, and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB).

Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs.

Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence.

Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB.

Objectives: (1) To determine the duration of androgen deprivation after a single buserelin implant 9.45 mg in the neoadjuvant setting in combination with curative radiation therapy of carcinoma of the prostate, and (2) to evaluate the time to recovery of gonadal function, and the incidence and duration of hypogonadal symptoms. Methods: We prospectively evaluated 21 men with carcinoma of the prostate who received one implant of 9.45 mg buserelin subcutaneously. Release of buserelin, changes in serum testosterone concentration, hot flushing and sexual function over a 12-month study period were recorded. Results: Testosterone was suppressed below the castration limit (0.58 ng/ml = 2 nmol/l) for 224 days (range, 139-309). The mean time to first return of testosterone above the castration limit was 246 days (range, 168-344), 50% of pre-treatment value was reached after 285 days (range, 218-370). The prevalence of hot flushing was 19 of 21 patients (90%) at 12 weeks. At the end of the study period, serum testosterone had reached 80% (range, 33%-166%) of pre-treatment concentration, sexual interest was present in 52%, erection was possible in 60%, and hot flushing remained in 24%. Conclusion: A single injection of 3-month buserelin implant 9.45 mg suppresses serum testosterone below the castration limit for at least 6 months. Testosterone secretion recovers by 8-12 months. Hypogonadal symptoms decreased with the restoration of serum testosterone secretion. These data are clinically relevant regarding the dose schedule for buserelin and the patient information provided. © 2006 European Association of Urology.

Objective: To evaluate the disease-specific mortality of conservatively managed incidental carcinoma of the prostate (T1a and T1b) in relation to prognostic factors.

Material and methods: Since 1987 all patients with prostate cancer have been recorded and followed in the population-based Prostate Cancer Register of the South-East Healthcare Region in Sweden, which is covered by four departments of pathology. At two of these departments, tissue was obtained from 197 consecutive, previously untreated patients (aged <80 years) with incidental carcinoma who underwent transurethral resection of the prostate between 1987 and 1991. The amount of tumour, Gleason score and levels of Ki-67, p53, chromogranin A and serotonin were determined. Univariate analysis and multiple Cox regression hazard analysis were used for analysis.

Results: During follow-up (mean 7.8 years; maximum 17.5 years), 158 patients (80%) had died, 33 of them of prostate cancer, corresponding to 17% of the entire cohort. Of 86 patients with Gleason score ≤5, three died of prostate cancer. Independent predictors of disease-specific mortality in multivariate analysis were category T1b prostate cancer, Gleason score >5 and high immunoreactivity of Ki-67.

Conclusions: Elderly men with category T1a and/or Gleason score 4-5 prostate cancer have a favourable prognosis with conservative management. Immunohistochemical staining with Ki-67 may be of help in situations where further prognostic information is required.

Objectives: To assess the value of prostate-specific antigen (PSA) kinetics in predicting survival and relate this to the baseline variables in men with metastatic hormone-refractory prostate cancer (HRPC).

Methods: The data from 417 men with HRPC were included in a logistic regression model that included hemoglobin, PSA, alkaline phosphatase, Soloway score, and performance status pain analgesic score at baseline. The posttreatment variables included the PSA level halving time after the start of treatment, PSA level at nadir, interval to nadir, PSA velocity (PSAV), PSA doubling time after reaching a nadir, patient age, and treatment. These variables were added to the baseline model, forming new logistic regression models that were tested for net reclassification improvement.

Results: The area under the receiver operating characteristics curve for the baseline model was 0.67. Of all variables related to PSA kinetics, the PSAV was the best predictor. The addition of PSAV to the baseline model increased the area under the receiver operating characteristics curve to 0.81. Only a moderate increase in the area under the receiver operating characteristics curve (0.83) was achieved by combining the baseline model in a multivariate model with PSAV, PSA doubling time, interval to nadir, and patient age at diagnosis of HRPC.

Conclusions: The PSAV alone gave a better prediction of survival value than all other PSA kinetics variables. By combining PSAV with the variables available at baseline, a better ground for treatment decision-making in men with HRPC can be achieved.

Purpose: We determined how serial measurements of prostate specific antigen and alkaline phosphatase can be used to predict survival early in the course of hormone treated metastatic prostate cancer.

Materials and Methods: The study was based on a prospective randomized trial of 915 patients with metastatic prostate carcinoma designed to compare parenteral estrogen (polyestradiol phosphate) vs total androgen blockade. We included 697 men who survived at least 6 months and had complete serial measurements of prostate specific antigen and alkaline phosphatase. Six models were constructed based on prostate specific antigen and alkaline phosphatase at start, and after 6 months of treatment, alkaline phosphatase flare and relative prostate specific antigen velocity. We constructed time dependent receiver operating characteristic curves with corresponding area under the curve to predict death from prostate cancer within 3 years.

Results: The best variables to predict outcome were alkaline phosphatase at 6 months (AUC 0.79 for polyestradiol phosphate and 0.72 for total androgen blockade), alkaline phosphatase at baseline (AUC 0.70 for polyestradiol phosphate and total androgen blockade) and prostate specific antigen at 6 months (AUC 0.70 for polyestradiol phosphate and total androgen blockade). Prostate specific antigen and alkaline phosphatase levels 6 months after start of treatment give better prediction of survival than baseline levels.

Conclusions: Alkaline phosphatase at start of treatment and alkaline phosphatase and prostate specific antigen after 6 months can be used to predict survival of hormone treated metastatic prostate cancer.

Objective. This study evaluated the impact of hospital volume on local recurrence and distant metastasis in a population-based series of radical cystectomy patients in Sweden. Material and methods. All patients who underwent cystectomy for bladder cancer in 1997-2002 in Sweden and were reported to the National Bladder Cancer Registry were included. A high-volume hospital (HVH) was defined as one with greater than= 10 cystectomies/year and a low-volume hospital (LVH) as one with less than10 cystectomies/year. Information on preoperative tumour, node, metastasis (TNM) classification, operative procedure, postoperative course and follow-up was obtained from medical records. Results. Of the 1126 patients, 827 (74%) were males. The mean age was 66 years and median follow-up 47 months. Of the 610 (54%) HVH patients, 68 (11%) were pT0, 123 (20%) less thanpT2, 177 (29%) pT2, 242 (40%) greater thanpT2 and 69 (11%) were microscopic non-radical. Corresponding figures for the 516 (46%) LVH patients were 35 (7%), 68 (13%), 191 (37%), 222 (43%) and 96 (19%). Local recurrence was observed in 245 patients (22%): 113 (19%) at HVHs and 132 (26%) at LVHs. Distant metastasis was found in 363 (32%): 203 (33%) at HVHs and 160 (31%) at LVHs. Perioperative chemotherapy was given to 193 (17%). Multivariate Cox proportional hazards analysis showed that local recurrence was associated with LVHs and non-organ-confined disease, whereas distant metastasis was correlated with non-organ-confined disease and lymph-node metastases. Conclusions. In this retrospective analysis, local tumour recurrence after cystectomy was common, particularly in patients with non-organ-confined disease. Furthermore, local recurrence was more frequent at LVHs than HVHs, and overall survival was better at HVHs. These findings suggest that concentrating cystectomies in HVHs may improve outcomes such as local recurrence and overall survival.

BACKGROUND. To evaluate the predictive value of prostate-specific antigen (PSA) in a population-based cohort, the authors analyzed relative survival in all men with localized prostate cancer who were registered in the Swedish National Prostate Cancer Register (NPCR) from 1996 to 2005. METHODS. All men aged <75 years with localized tumors were identified in the NPCR. A Poisson regression analysis was performed using observed death as response and the expected death rate as offset. The expected and observed numbers of survivors were calculated with stratification for PSA level and 3 categories of tumor differentiation (Gleason score 2-6, 7, and 8-10). The regression model included PSA as linear splines with a breakpoint at a PSA level of 4 ng/mL and with tumor differentiation as a categoric variable. RESULTS. The Poisson regression analysis indicated a U-shaped curve for all 3 groups, with a negative correlation between PSA and relative survival in men with PSA levels <4 ng/mL and a positive correlation for men with PSA levels >4 ng/mL. The correlation was significant for all 3 groups, but the negative correlation between PSA and relative survival was significantly more pronounced in the group with Gleason scores from 8 to 10 than in the other 2 Gleason score groups. CONCLUSIONS. The demonstration of an inverse correlation between PSA level and relative survival in the group of men with PSA levels <4 ng/mL indicated the presence of a small but clinically important subgroup with undifferentiated tumors who have cells that have lost the ability to secrete PSA. This group should be taken into consideration when deciding on treatment and when choosing a cutoff level in PSA screening programs. © 2007 American Cancer Society.

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Objective To assess whether screening for prostate cancer reduces prostate cancer specific mortality. Design Population based randomised controlled trial. Setting Department of Urology, Norrkoping, and the South-East Region Prostate Cancer Register. Participants All men aged 50-69 in the city of Norrkoping, Sweden, identified in 1987 in the National Population Register (n=9026). Intervention From the study population, 1494 men were randomly allocated to be screened by including every sixth man from a list of dates of birth. These men were invited to be screened every third year from 1987 to 1996. On the first two occasions screening was done by digital rectal examination only. From 1993, this was combined with prostate specific antigen testing, with 4 mu g/L as cut off. On the fourth occasion (1996), only men aged 69 or under at the time of the investigation were invited. Main outcome measures Data on tumour stage, grade, and treatment from the South East Region Prostate Cancer Register. Prostate cancer specific mortality up to 31 December 2008. Results In the four screenings from 1987 to 1996 attendance was 1161/1492 (78%), 957/1363 (70%), 895/1210 (74%), and 446/606 (74%), respectively. There were 85 cases (5.7%) of prostate cancer diagnosed in the screened group and 292 (3.9%) in the control group. The risk ratio for death from prostate cancer in the screening group was 1.16 (95% confidence interval 0.78 to 1.73). In a Cox proportional hazard analysis comparing prostate cancer specific survival in the control group with that in the screened group, the hazard ratio for death from prostate cancer was 1.23 (0.94 to 1.62; P=0.13). After adjustment for age at start of the study, the hazard ratio was 1.58 (1.06 to 2.36; P=0.024). Conclusions After 20 years of follow-up the rate of death from prostate cancer did not differ significantly between men in the screening group and those in the control group.

Background: Current prostate cancer prognostic models are based on pre-treatment prostate specific antigen (PSA) levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models. Methods: We analyzed a Swedish Watchful Waiting cohort with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL) method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP) samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer and men who survived more than 10 years without metastases (lethals and indolents, respectively). Several statistical and machine learning models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases. Results: Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors. Conclusions: The determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses making the development of molecular biomarkers for prostate cancer progression challenging.

OBJECTIVE:

In two previous studies we calculated direct costs for men with prostate cancer who died in 1984-85 and 1992-93, respectively. We have now performed a third cost analysis to enable a longitudinal cost comparison. The aim was to calculate direct costs for the management of prostate cancer, describe the economic consequences of technological changes over time and estimate total direct costs for prostate cancer in Sweden.

MATERIAL AND METHODS:

A total of 204 men in a defined population with a diagnosis of prostate cancer and who died in 1997-98 were included. Data on utilization of health services were extracted from clinical records from time of diagnosis to death from a university hospital and from one county hospital in the county of Ostergötland.

RESULTS:

The average direct cost per patient has been nearly stable over time (1984-85: 143 000 SEK; 1992-93: 150 000 SEK; 1997-98: 146 000 SEK). The share of costs for drugs increased from 7% in 1992-93 to 17% in 1997-98. The total direct costs for prostate cancer in Sweden have increased over time (1994-85: 610 MSEK; 1992-93: 860 MSEK; 1997-98: 970 MSEK).

CONCLUSIONS:

Two-thirds of the total cost is incurred by inpatient care. The share of the total costs for drugs is increasing due to increased use of gonadotrophin-releasing hormone analogues. Small changes in average direct costs per patient despite greater use of technology are explained by the fact that more prostate cancers are detected at the early stages.

OBJECTIVE:

To estimate the lifetime cost per detected potentially curable cancer and the economic impact on healthcare of repeated screening for prostate cancer in Sweden in a cohort of men aged 50-69 years.

MATERIAL AND METHODS:

All 9171 men in a geographically defined population were included: 1492 were randomized to screening in four rounds every third year and 7679 constituted a control group. Digital rectal examination and prostate-specific antigen screening in different combinations were used as diagnostic measures. Costs associated with administration of the screening programme, loss of patient time, diagnostic measures and management strategies were included. A decision model was developed to calculate the total cost of the programme.

RESULTS:

The incremental cost per extra detected localized cancer was 168,000 SEK and per potentially curable cancer 356,000 SEK. Introducing this screening programme for prostate cancer in Sweden would incur 244 million SEK annually in additional costs for screening and treatment compared to a non-screening strategy.

CONCLUSION:

There is still no scientific evidence that patients will benefit from screening programmes. Prostate cancer screening would probably be perceived as cost-effective if potentially curable patients gained on average at least 1 year of survival.

Background: The majority of prostate cancers harbor gene fusions of the 5′-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. Methods: We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians' Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. Results: We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81, P <. 001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERβ agonist (ERβ agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ERα agonist treatment (ERα agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ERβ agonist treatment (fold change over internal control, ERβ agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ERα agonist treatment (ERα agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). Conclusions: TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism. © The Author 2008. Published by Oxford University Press.

Abstract Not Available

Godartad prostataförstoring med avflödeshinder är en vanlig sjukdom. Försäljningen av ­l­äkemedel i Sverige motsvarar kontinuerlig behandling av 100 000 män. Antalet operationer per år är 4 500.

SBU publicerade 2011 en systematisk litteraturgranskning av området.

En stor del av handläggningen kan ske i primärvården. Patienterna behandlas i regel på sannolikhetsdiagnos och endast ett fåtal gör tryck–flödes­undersökning som kan ge säker diagnos.

Vid lindriga besvär krävs ingen behandling. Vid måttliga–­svåra besvär står valet mellan en mindre effektiv och lindrig behandling, läkemedel, och en besvärligare men också mycket effektivare kirurgisk behandling.

Objective. To investigate the geographical variation in prostate cancer incidence in Sweden, in particular the incidences of screening-detected tumours and curative treatment of prostate cancer. Material and methods. Data were retrieved from the National Prostate Cancer Register of Sweden for all cases of prostate cancer diagnosed in the year 2000-01. There were a total of 14376 cases of prostate cancer and the mean total annual age-adjusted incidence was 197/100000 men. There were 3318 cases in tumour category T1c, i.e. non-palpable tumours diagnosed during work-up for an elevated serum level of prostate-specific antigen, 1006 of which (30%) were asymptomatic and detected at a health check-up. Results. The difference between the counties with the lowest and highest age-adjusted incidences per 1OO 000 men of total prostate cancer was almost twofold (128 vs 217). The corresponding variation in incidence of category Tie tumours was more than fourfold (13 vs 60), the difference in incidence of Tie tumours detected in asymptomatic men was up to 10-fold (2 vs 20), and there was more than a fourfold variation in incidence of curative treatment between counties (13 vs 67). Measured incidences were mostly highest in urban regions and in counties with university hospitals. Conclusion. There are large geographical variations in prostate cancer incidence and in the frequency of curative treatment for prostate cancer in Sweden and there appear to be large geographical variations in the uptake of prostate cancer screening. © 2005 Taylor & Francis.

OBJECTIVE To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS During their follow-up we attempted to contact all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with freehand comments. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers andgt; 96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of andlt; 3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

Approximately 15% of men with hormone naive metastatic prostate cancer primarily fail to respond to androgen deprivation treatment (ADT). The reason why the response to ADT differs in this subgroup of men with prostate cancer remains unclear. The aim of this study was to describe the characteristics of these men and to thereby define predictors of early ADT failure in prostate cancer patients with bone metastases. The study was based on 915 men from the prospective randomized multicenter trial (no. 5) conducted by the Scandinavian Prostate Cancer Group comparing parenteral estrogen with total androgen blockade. Early ADT failure was defined as death from metastatic prostate cancer within 12months after the start of ADT. Multivariate logistic regression models were applied to identify clinical predictors of early ADT failure. Ninety-four (10.3%) men were primarily nonresponders to ADT. Independent predictors of early ADT failure were poor Eastern Cooperative Oncology Group performance status (PS), analgesic consumption, low hemoglobin, and high Soloway score (extent of disease observed on the scan), in where patients with poor PS and/or high analgesic consumption had a threefold risk of early ADT failure. Not significantly factors related to early ADT failure were age, treatment, cardiovascular comorbidity, T category, grade of malignancy, serum estrogen level, and SHBG at enrolment. We analyzed characteristics of a subgroup of patients who primarily failed to respond to ADT. Four independent clinical predictors of early ADT failure could be defined, and men exhibiting these features should be considered for an alternative treatment.

Objective. Infravesical obstruction leads to growth of urinary bladder smooth-muscle cells. The ganglion cells innervating the bladder muscle also increase in size. Stretch of detrusor muscle cells rapidly activates c-Jun NH₂-terminal kinase (JNK), which phosphorylates the transcription factor c-Jun, and stimulates the synthesis of the cotranscription factor ATF3. The aim of the study was to determine whether ATF3 and p-c-Jun were involved in growth of bladder smooth-muscle and ganglion cells. Material and methods. The urethra was partially obstructed in female rats. After 3 days or 10 weeks bladders were weighed, fixated and cut for immunohistochemistry to demonstrate ATF3 and p-c-Jun. Ganglia were processed separately. Unoperated and sham-operated rats were used as controls. Results. There was no ATF3 or p-c-Jun in control detrusor muscle. After 3 days of obstruction bladder weight had nearly doubled. Almost all nuclei in the detrusor showed immunofluorescence for ATF3 and p-c-Jun. After 10 weeks bladder weight had increased 10-fold. Almost all detrusor nuclei still showed p-c-Jun, but few had ATF3 activity. In control ganglia there was no ATF3 and only faint nuclear p-c-Jun activity. After 3 days of obstruction the ganglion cells had increased in size and many nuclei showed intense immunofluorescence for ATF3 and p-c-Jun. After 10 weeks the ganglion cell size had increased further. There was no ATF3 activity and no more p-c-Jun than in control ganglia. Conclusion. ATF3 and p-c-Jun seem to be involved in the growth of the detrusor muscle and its motor innervation following infravesical outlet obstruction.