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1.
  • Van Hemelrijck, Mieke, et al. (författare)
  • Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium
  • Ingår i: European Urology. - : Elsevier. - 0302-2838. ; 75:3, s. 523-531
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4–28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0–13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5–2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4–2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for <5 yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4–28.6%) at 5 yr and 38.2% (95% CI: 36.7–39.9%) at 10 yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up. Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS.
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2.
  • Robinson, David, et al. (författare)
  • Ischemic heart disease and stroke before and during endocrine treatment for prostate cancer in PCBaSe Sweden
  • 2012
  • Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 130:2, s. 478-487
  • Tidskriftsartikel (refereegranskat)abstract
    • In observational studies of men with prostate cancer, men on endocrine treatment (ET) have had an increased risk of ischemic heart disease (IHD) and stroke. However, prostate cancer per se may increase risk of IHD and stroke and men on ET may have been at increased risk already prior to initiation of ET. We assessed the incidence of IHD and stroke in men with prostate cancer before and during different endocrine treatments. The hazard ratio (HR) of IHD and stroke in 39,051 men with prostate cancer vs. a matched control population without prostate cancer was assessed by use of Cox proportion hazard models. An increased risk was found among 30,883 men with prostate cancer who did not receive ET, with a HR of 1.08 (95% CI 1.00–1.18) for IHD and 1.10 (95%CI 1.00–1.21) for stroke. In 8,168 men who initiated ET during the observation period, the risk of IHD was significantly higher (p = 0.014), during ET (HR 1.40, 95% CI 1.17–1.67) compared with before initiation of ET (HR of 0.98, 95% CI 0.72–1.33), whereas no such increase was found for stroke. Regardless of treatment, men with prostate cancer had a small increase in risk of IHD and stroke and initiation of ET was associated with a further increase in risk of IHD. Our data underline the importance of a proper indication for ET because many men with low-risk prostate cancer currently receive ET.
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3.
  • Van Hemelrijck, Mieke, et al. (författare)
  • Mortality following Hip Fracture in Men with Prostate Cancer
  • 2013
  • Ingår i: PLoS ONE. - : PLoS. - 1932-6203 .- 1932-6203. ; 8:9, s. e74492-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hip fractures are associated with increased mortality and are a known adverse effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). It was our aim to evaluate how mortality after hip fracture is modified by PCa and ADT.Methods: PCa dataBase Sweden (PCBaSe 2.0) is based on the National PCa Register and also contains age and county-matched PCa-free men. We selected all men (n = 14,205) who had been hospitalized with a hip fracture between 2006 and 2010; 2,300 men had a prior PCa diagnosis of whom 1,518 (66%) were on ADT prior to date of fracture. Risk of death was estimated with cumulative incidence and standardized mortality ratios (SMRs) to make comparisons with the entire PCa population and the general population.Results: Cumulative incidences indicated that there was a higher risk of death following a hip fracture for PCa men on ADT than for PCa men not on ADT or PCa-free men, particularly in the first year. The SMRs showed that PCa men on ADT with a hip fracture were 2.44 times more likely to die than the comparison cohort of all PCa men (95% CI: 2.29-2.60). This risk was especially increased during the first month (5.64 (95% CI: 4.16-7.48)). In absolute terms, hip fractures were associated with 20 additional deaths per 1,000 person-years in PCa men not on ADT, but 30 additional deaths per 1,000 person-years for PCa men on ADT, compared to all PCa men.Conclusion: Hip fractures are associated with higher all-cause mortality in PCa men on ADT than in PCa men not on ADT or PCa-free men, especially within the first three months.
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4.
  • Van Hemelrijck, Mieke, et al. (författare)
  • Multiple events of fractures and cardiovascular and thromboembolic disease following prostate cancer diagnosis : results from the population-based PCBaSe Sweden
  • 2012
  • Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 61:4, s. 690-700
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To date, adverse events of prostate cancer (PCa) treatment have only been studied as a single event, and little is known about the risk of subsequent adverse events. OBJECTIVE: We assessed the frequency of multiple events (fractures, stroke, heart disease [HD], and thromboembolic disease [TED]) following PCa diagnosis. DESIGN, SETTING, AND PARTICIPANTS: PCBaSe Sweden is based on the National Prostate Cancer Register (NPCR) that covers >96% of incident PCa cases in Sweden. MEASUREMENTS: We evaluated the number of events (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the National Hospital Discharge Registry after PCa diagnosis and conducted multivariate age-adjusted Cox proportional hazards regression to estimate the risk of developing multiple events. RESULTS AND LIMITATIONS: Between 1997 and 2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment, and 19 526 surveillance: 75% had no event during follow-up, 17% had one event, and 9% had more than one event. The incidence of any event was 102 in 1000 person-years. Men who already had experienced an event, particularly HD, before or after the date of PCa diagnosis were more likely to have multiple events afterwards. For example, the hazard ratio of developing a third event for those with two or more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28-1.52) compared with those with no events of HD before PCa diagnosis. Events treated without hospitalisation were not included, so the number of adverse events is possibly underestimated. CONCLUSIONS: A third of PCa patients with an adverse event after treatment subsequently experienced another adverse event, but apart from history of HD or stroke before PCa diagnosis, no specific characteristics were found for these men. Thus PCa management needs to take into account the risk of adverse events in all PCa patients, especially those with a history of adverse events before PCa diagnosis.
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5.
  • Van Hemelrijck, Mieke, et al. (författare)
  • Primary Cancers Before and After Prostate Cancer Diagnosis
  • 2012
  • Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 118:24, s. 6207-6216
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The occurrence of multiple cancers may indicate common etiology; and, although some studies have investigated the risk of second primary cancers after prostate cancer (PCa), there are no studies on cancers before PCa. METHODS: The PCBaSe Sweden database is based on the National Prostate Cancer Register (NPCR), which covers >96% of PCa cases. The authors estimated the prevalence and cumulative incidence of different cancers before and after PCa diagnosis in 72,613 men according to PCa treatment and disease stage in PCBaSe and their matched comparison cohort of men who were free of PCa. RESULTS: In total, 6829 men were diagnosed with another primary cancer before their PCa diagnosis, including 138 men at the time of PCa diagnosis and 5230 men were diagnosed after PCa diagnosis. Cancer of the bladder or colon and nonmelanoma of the skin were the 3 most frequently observed cancers before and after PCa diagnosis. At the time of PCa diagnosis, the prevalence of these 3 cancers was 1.94% for bladder cancer, 1.08% for colon cancer, and 1.08% for nonmelanoma skin cancer, compared with 1.30%, 0.96%, and 1.03%, respectively, for the matched comparison cohort. Five years after PCa diagnosis, the difference in incidence proportion between PCa men and their comparison cohort was 7% (95% CI, 5.6%-8.5%), 1.3% (0%-2.6%), and 1.6% (0.6%-2.6%) for these 3 cancers, respectively. From a uro-oncologic point of view, it is interesting to note that the prevalence of kidney cancer at the time of PCa diagnosis was 0.42% compared with 0.28% for the matched comparison cohort. CONCLUSIONS: Approximately 17% of all PCa occurred in combination with another primary cancer (before or after PCa diagnosis). Detection bias probably explains part of this observation, but further investigations are required to assess possible underlying mechanisms. 
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6.
  • Van Hemelrijck, Mieke, et al. (författare)
  • Thromboembolic events following surgery for prostate cancer
  • 2013
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 63:2, s. 354-363
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prostate cancer (PCa) and surgery are both associated with increased risk of thromboembolic diseases (TED). Objective: We assessed risk of TED among men undergoing different types of urologic surgery. Design, setting, and participants: Using the Prostate Cancer Database Sweden (PCBaSe) Sweden, we identified all men (n = 45 065) undergoing pelvic lymph node dissection (PLND), radical prostatectomy (RP) with or without PLND, orchiectomy due to PCa, or a transurethral resection of the prostate (TURP). We identified a comparison cohort from the population. Outcome measurements and statistical analysis: Main outcomes were deep venous thrombosis (DVT) and pulmonary embolism (PE) as primary diagnoses in the National Patient Register or Cause of Death Register (2002-2010). We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazards models. Results and limitations: All surgical procedures were associated with increased risk of TED; laparoscopic and open RP with a PLND were the most strongly associated with TED (HR for PE: 8.1 [95% CI, 2.9-23.0] and 7.8 [95% CI, 4.9-13], respectively). For surgery including a PLND, the risk increased during the second half of the first postoperative month. The HR for PE after TURP in men with PCa was 3.0 (95% CI, 1.8-5.1). Patients with a history of TED had a strongly increased risk of TED (HR for DVT: 4.5; 95% CI, 2.6-8.0). A limitation is lack of information on TED prophylaxis, but its use was standardized during the study period for RP and PLND. Other limitations are lack of information on extent of PLND and lifestyle factors. Conclusions: Surgeries for PCa, including TURP, are associated with hospitalization for TED. Patients with a history of TED and patients undergoing a PLND were at highest risk. The largest risk was observed from days 14 to 28 postoperatively. Thus, our results suggest that prophylactic measures may be beneficial during the first 4 wk in these patients. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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7.
  • Robinson, D., et al. (författare)
  • Androgen deprivation therapy for prostate cancer and risk of dementia
  • 2019
  • Ingår i: Bju International. - 1464-4096 .- 1464-410X. ; 124:1, s. 87-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To study whether androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia. Methods Risk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in the Prostate Cancer Database Sweden, PCBaSe, was compared with that in prostate cancer-free men, matched on birth year and county of residency. We used Cox regression to calculate the hazard ratios (HRs) for Alzheimer's and non-Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens (AAs) as well as for men managed with WW. Results A total of 25 967 men with prostate cancer and 121 018 prostate cancer-free men were followed for a median of 4 years. In both groups 6% of the men were diagnosed with dementia. In men with prostate cancer, gonadotropin-releasing hormone agonist treatment ( HR 1.15, 95% confidence interval [CI] 1.07-1.23) and orchiectomy (HR 1.60, 95% CI 1.32-1.93) were associated with an increased risk of dementia, as compared to no treatment in prostate cancer-free men; however, this increase in risk was only observed for non-Alzheimer's dementia and occurred from year 1-4 after start of ADT. No increase in risk for any type of dementia was observed for men treated with AAs or for men on WW. Conclusion This population-based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT; however, there was a small increase in risk of non-Alzheimer's dementia.
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8.
  • Omar, Muhammad Imran, et al. (författare)
  • Introducing PIONEER: a project to harness big data in prostate cancer research.
  • 2020
  • Ingår i: Nature reviews. Urology. - : Nature Publishing Group. - 1759-4820 .- 1759-4812. ; 17:6, s. 351-362
  • Forskningsöversikt (refereegranskat)abstract
    • Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate cancer management by unlocking the potential of big data. The project has identified critical evidence gaps in prostate cancer care, via a detailed prioritization exercise including all key stakeholders. By standardizing and integrating existing high-quality and multidisciplinary data sources from patients with prostate cancer across different stages of the disease, the resulting big data will be assembled into a single innovative data platform for research. Based on a unique set of methodologies, PIONEER aims to advance the field of prostate cancer care with a particular focus on improving prostate-cancer-related outcomes, health system efficiency by streamlining patient management, and the quality of health and social care delivered to all men with prostate cancer and their families worldwide.
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9.
  • Ahlberg, Mats Steinholtz, et al. (författare)
  • PCASTt/SPCG-17-A randomised trial of active surveillance in prostate cancer: Rationale and design
  • 2019
  • Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.
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10.
  • Arthur, Rhonda, et al. (författare)
  • Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories
  • 2016
  • Ingår i: Cancer Medicine. - 2045-7634 .- 2045-7634. ; 5:6, s. 1307-1318
  • Tidskriftsartikel (refereegranskat)abstract
    • Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 mu g/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 mu g/L compared to PSA 4.0-9.9 mu g/L. Hypertriglyceridemia was also positively associated with PSA>20 mu g/L. Hyperglycemic men had a greater odds of intermediate-and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention.
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