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  • Wulaningsih, W., et al. (författare)
  • A competing risks analysis of the association between prediagnostic serum glucose and lipids and breast cancer survival
  • 2016
  • Ingår i: Cancer Research. - Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London WC2R 2LS, England. Kings Coll London, Inst Math & Mol Biomed, London WC2R 2LS, England. Uppsala Univ, Uppsala, Sweden. Reg Canc Ctr, Uppsala, Sweden. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Karolinska Inst, S-10401 Stockholm, Sweden. AstraZeneca R&D, Mlndal, Switzerland. CALAB Res, Madrid, Spain.. - 0008-5472 .- 1538-7445. ; 76
  • Tidskriftsartikel (övrigt vetenskapligt)
  • Rowley, M., et al. (författare)
  • A latent class model for competing risks
  • 2017
  • Ingår i: Statistics in Medicine. - 0277-6715 .- 1097-0258. ; 36:13, s. 2100-2119
  • Tidskriftsartikel (refereegranskat)abstract
    • Survival data analysis becomes complex when the proportional hazards assumption is violated at population level or when crude hazard rates are no longer estimators of marginal ones. We develop a Bayesian survival analysis method to deal with these situations, on the basis of assuming that the complexities are induced by latent cohort or disease heterogeneity that is not captured by covariates and that proportional hazards hold at the level of individuals. This leads to a description from which risk-specific marginal hazard rates and survival functions are fully accessible, 'decontaminated' of the effects of informative censoring, and which includes Cox, random effects and latent classmodels as special cases. Simulated data confirm that our approach can map a cohort's substructure and remove heterogeneity-induced informative censoring effects. Application to data from the Uppsala Longitudinal Study of Adult Men cohort leads to plausible alternative explanations for previous counter-intuitive inferences on prostate cancer. The importance of managing cardiovascular disease as a comorbidity in women diagnosed with breast cancer is suggested on application to data from the Swedish Apolipoprotein Mortality Risk Study.
  • Haggstrom, C., et al. (författare)
  • Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer
  • 2017
  • Ingår i: Int J Cancer. - 0020-7136 .- 1097-0215. ; 140:3, s. 611-617
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD = 9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD = 3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR = 0.85, 95% CI = 0.82-0.88) but among men with T2DM, those on metformin had no decrease (HR = 0.96, 95% CI = 0.77-1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR = 0.73, 95% CI = 0.55-0.98), compared to men with T2DM not on anti-diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR = 1.11, 95% CI = 0.95-1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.
  • Kinsella, N., et al. (författare)
  • Factors Influencing Men's Choice of and Adherence to Active Surveillance for Low-risk Prostate Cancer: A Mixed-method Systematic Review
  • 2018
  • Ingår i: European Urology. - : ELSEVIER SCIENCE BV. - 0302-2838 .- 1873-7560. ; 74:3, s. 261-280
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Despite support for active surveillance (AS) as a first treatment choice for men with low-risk prostate cancer (PC), this strategy is largely underutilised. Objective: To systematically review barriers and facilitators to selecting and adhering to AS for low-risk PC. Evidence acquisition: We searched PsychINFO, PubMed, Medline 2000-now, Embase, CINAHL, and Cochrane Central databases between 2002 and 2017 using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The Purpose, Respondents, Explanation, Findings and Significance (PREFS) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) quality criteria were applied. Forty-seven studies were identified. Evidence synthesis: Key themes emerged as factors influencing both choice and adherence to AS: (1) patient and tumour factors (age, comorbidities, knowledge, education, socioeconomic status, family history, grade, tumour volume, and fear of progression/side effects); (2) family and social support; (3) provider (speciality, communication, and attitudes); (4) healthcare organisation (geography and type of practice); and (5) health policy (guidelines, year, and awareness). Conclusions: Many factors influence men's choice and adherence to AS on multiple levels. It is important to learn from the experience of other chronic health conditions as well as from institutions/countries that are making significant headway in appropriately recruiting men to AS protocols, through standardised patient information, clinician education, and nationally agreed guidelines, to ultimately decrease heterogeneity in AS practice. Patient summary: We reviewed the scientific literature for factors affecting men's choice and adherence to active surveillance (AS) for low-risk prostate cancer. Our findings suggest that the use of AS could be increased by addressing a variety of factors such as information, psychosocial support, clinician education, and standardised guidelines. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • 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.
  • Van Hemelrijck, Mieke, et al. (författare)
  • Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium
  • 2019
  • 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.
  • Wulaningsih, Wahyu, et al. (författare)
  • Prediagnostic serum glucose and lipids in relation to survival in breast cancer patients : a competing risk analysis
  • 2015
  • Ingår i: BMC Cancer. - 1471-2407 .- 1471-2407. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Abnormal glucose and lipids levels may impact survival after breast cancer (BC) diagnosis, but their association to other causes of mortality such as cardiovascular (CV) disease may result in a competing risk problem. Methods: We assessed serum glucose, triglycerides (TG) and total cholesterol (TC) measured prospectively 3 months to 3 years before diagnosis in 1798 Swedish women diagnosed with any type of BC between 1985 and 1999. In addition to using Cox regression, we employed latent class proportional hazards models to capture any heterogeneity of associations between these markers and BC death. The latter method was extended to include the primary outcome (BC death) and competing outcomes (CV death and death from other causes), allowing latent class-specific hazard estimation for cause-specific deaths. Results: A lack of association between prediagnostic glucose, TG or TC with BC death was observed with Cox regression. With latent class proportional hazards model, two latent classes (Class I and II) were suggested. Class I, comprising the majority (81.5 %) of BC patients, had an increased risk of BC death following higher TG levels (HR: 1.87, 95 % CI: 1.01-3.45 for every log TG increase). Lower overall survival was observed in Class II, but no association for BC death was found. On the other hand, TC positively corresponded to CV death in Class II, and similarly, glucose to death from other causes. Conclusion: Addressing cohort heterogeneity in relation to BC survival is important in understanding the relationship between metabolic markers and cause-specific death in presence of competing outcomes.
  • Arthur, R., et al. (författare)
  • Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study
  • 2018
  • Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:11, s. 2254-2262
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.
  • 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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