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  • 1.
    Akre, Olof
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Garmo, Hans
    Regional Oncological Center, Uppsala, Sweden.
    Adolfsson, Jan
    Oncological Center, CLINTEC Department, Karolinska Institutet, Stockholm, Sweden.
    Lambe, Mats
    Oncological Center, CLINTEC Department, andDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bratt, Ola
    Department of Urology, Helsingborg Hospital, Lund University, Sweden.
    Stattin, Pär
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Mortality Among Men with Locally Advanced Prostate Cancer Managed with Noncurative Intent: A Nationwide Study in PCBaSe Sweden2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 3, p. 554-563Article in journal (Refereed)
    Abstract [en]

    Background

    There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment.

    Objective

    To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent.

    Design, setting, and participants

    We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis.

    Measurements

    We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics.

    Results and limitations

    The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA < 4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status.

    Conclusions

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 2.
    Arthur, R.
    et al.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
    Williams, R.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Malmstrom, H.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum, Stockholm, Sweden.
    Lambe, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Hammar, N.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;AstraZeneca, Global Med Dev Med Evidence & Observat Res, Stockholm, Sweden.
    Walldius, G.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Robinsson, D.
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Jungner, I.
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden;CALAB Res, Stockholm, Sweden.
    Van Hemelrijck, M.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 11, p. 2254-2262Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Ax, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Garmo, Hans
    Regional Cancer Center , Uppsala University Hospital , Uppsala , Sweden.
    Grundmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Becker, Wulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary Patterns and Prostate Cancer Risk: Report from the Population Based ULSAM Cohort Study of Swedish Men2014In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 66, no 1, p. 77-87Article in journal (Refereed)
    Abstract [en]

    Dietary pattern analyses have increased the possibilities to detect associations between diet and disease. However, studies on dietary pattern and prostate cancer are scarce. Food intake data in the Uppsala Longitudinal Study of Adult Men cohort was determined by 7-day food records. Adherence to a modified Mediterranean Diet Score (mMDS) and a low carbohydrate-high protein (LCHP) score were grouped as low, medium, or high in the whole study population (n = 1,044) and in those identified as adequate reporters of energy intake (n = 566), respectively. Prostate cancer risk was analyzed with Cox proportional hazard regression (median follow-up 13years) and competing risk of death was considered. There were no associations between dietary patterns and prostate cancer (n = 133) in the whole study population. Among adequate reporters the mMDS was not associated with prostate cancer (n = 72). The LCHP score was inversely related to prostate cancer in adequate reporters, adjusted hazard ratios; 0.55 (0.32-0.96) for medium and 0.47 (0.21-1.04) for high compared to low adherent participants (P-for-trend 0.04). Risk relations were not attributable to competing risk of death. In this study, a LCHP diet was associated with lower prostate cancer incidence. Relations emerged in adequate reporters, underscoring the importance of high-quality dietary data.

  • 4.
    Ax, Erika Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Grundmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Wulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary Patterns and prostate cancer risk: a population based cohort study in elderly Swedish men2013In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 27, no S1, p. 847.8-Article in journal (Other academic)
  • 5.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 1, p. 35-40Article in journal (Refereed)
    Abstract [en]

    Introduction

    Seasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated.

    Aims

    To study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men.

    Methods

    Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test. Values were analyzed in linear regression models with an indicator variable for winter/summer season and outdoor temperature as predictors.

    Results

     During winter, insulin sensitivity (M/I, unit = 100 × mg × min-1 × kg-1/(mU × L-1)) was 11.0% lower (4.84 versus 5.44, P = 0.0003), incremental area under the insulin curve was 16.4% higher (1167 versus 1003 mU/L, P = 0.007). Fasting plasma glucose was, however, not statistically significantly different (5.80 versus 5.71 mmol/L, P = 0.28) compared to the summer season. There was an association between outdoor temperature and M/I (0.57 units increase (95% CI 0.29–0.82, P < 0.0001) per 10°C increase of outdoor temperature) independent of winter/summer season. Adjustment for life-style factors, type 2 diabetes, and medication did not alter these results.Read More:http://informahealthcare.com/doi/abs/10.3109/03009734.2011.628422

    Conclusions

    Insulin sensitivity showed seasonal variations with lower values during the winter and higher during the summer season. Inverse compensatory variations of insulin secretion resulted in only minor variations of fasting plasma glucose. Insulin sensitivity was associated with outdoor temperature. These phenomena should be further investigated in diabetic patients.

  • 6.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Garmo, Hans
    Lindbäck, Johan
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Maximum likelihood estimation of correction for dilution bias in simple linear regression using replicates from subjects with extreme first measurements2008In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 27, no 22, p. 4397-4407Article in journal (Refereed)
    Abstract [en]

    The least-squares estimator of the slope in a simple linear regression model is biased towards zero when the predictor is measured with random error. A corrected slope may be estimated by adding data from a reliability study, which comprises a subset of subjects from the main study. The precision of this corrected slope depends on the design of the reliability study and estimator choice.Previous work has assumed that the reliability study constitutes a random sample from the main study. A more efficient design is to use subjects with extreme values on their first measurement. Previously, we published a variance formula for the corrected slope, when the correction factor is the slope in the regression of the second measurement on the first. In this paper we show that both designs improve by maximum likelihood estimation (MLE). The precision gain is explained by the inclusion of data from all subjects for estimation of the predictor's variance and by the use of the second measurement for estimation of the covariance between response and predictor. The gain of MLE enhances with stronger true relationship between response and predictor and with lower precision in the predictor measurements. We present a real data example on the relationship between fasting insulin, a surrogate market, and true insulin sensitivity measured by a gold-standard euglycaemic insulin clamp, and simulations, where the behavior of profile-likelihood-based confidence intervals is examined. MLE was shown to be a robust estimator for non-normal distributions and efficient for small sample situations.

  • 7.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Regional Cancer Center, Uppsala-Örebro, Uppsala, Sweden.
    Holmberg, Lars
    King's College London, Medical School, Division of Cancer Studies, London, UK.
    Johansson, Jan-Erik
    Adami, Hans-Olov
    Steineck, Gunnar
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Rider, Jennifer R
    Long-term Distress After Radical Prostatectomy Versus Watchful Waiting in Prostate Cancer: A Longitudinal Study from the Scandinavian Prostate Cancer Group-4 Randomized Clinical Trial2013In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 64, no 6, p. 920-928Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups.

    OBJECTIVE:

    To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally.

    DESIGN, SETTING, AND PARTICIPANTS:

    The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up.

    INTERVENTION:

    RP compared with WW.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

    A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model.

    RESULTS AND LIMITATIONS:

    Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30-40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook.

    CONCLUSIONS:

    Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management.

  • 8.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala Univ, Uppsala, Sweden.
    Garmo, Hans
    Reg Canc Ctr Uppsala Örebro, Uppsala, Sweden.
    Radical Surgery or Watchful Waiting in Prostate Cancer Reply2019In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 380, no 11, p. 1084-1084Article in journal (Other academic)
  • 9.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Regional Cancer Center Uppsala Örebro.
    Garmo, Hans
    Regional Cancer Center Uppsala Örebro.
    Rider, Jennifer R.
    Taari, Kimmo
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nordling, Stig
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Andersson, Swen-Olof
    Spangberg, Anders
    Andren, Ove
    Palmgren, Juni
    Steineck, Gunnar
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, p. 932-942Article in journal (Refereed)
    Abstract [en]

    BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

  • 10.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Med, Div Canc Studies, London, England;Kings Coll London, Sch Canc & Pharmaceut Sci, London, England.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Sch Med, Div Canc Studies, London, England.
    Taari, Kimmo
    Helsinki Univ Hosp, Dept Urol, Helsinki, Finland.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Nordling, Stig
    Univ Helsinki, Dept Pathol, Helsinki, Finland.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Andersson, Swen-Olof
    Orebro Univ, Sch Hlth & Med Sci, Orebro, Sweden;Orebro Univ Hosp, Dept Urol, Orebro, Sweden.
    Andren, Ove
    Orebro Univ, Sch Hlth & Med Sci, Orebro, Sweden;Orebro Univ Hosp, Dept Urol, Orebro, Sweden.
    Steineck, Gunnar
    Sahlgrens Acad, Div Clin Canc Epidemiol, Gothenburg, Sweden.
    Adami, Hans-Olov
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Harvard TC Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Univ Oslo, Inst Hlth & Soc, Clin Effectiveness Res Grp, Oslo, Norway.
    Johansson, Jan-Erik
    Orebro Univ, Sch Hlth & Med Sci, Orebro, Sweden;Orebro Univ Hosp, Dept Urol, Orebro, Sweden.
    Radical Prostatectomy or Watchful Waiting in Prostate Cancer: 29-Year Follow-up2018In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 379, no 24, p. 2319-2329Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse.

    METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model.

    RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer).

    CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.

  • 11.
    Birgegård, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Folkvaljon, Folke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, London, England.
    Besses, Carlos
    Hosp del Mar, IMIM, Dept Haematol, Barcelona, Spain.
    Griesshammer, Martin
    Johannes Wesling Med Ctr, Hematol & Oncol, Minden, Germany.
    Gugliotta, Luigi
    St Orsola Malpighi Hosp, Dept Haematol L&A Seragnoli, Bologna, Italy.
    Wu, Jingyang
    Shire Pharmaceut, Global Biometr, Lexington, MA USA.
    Achenbach, Heinrich
    Shire GmbH, Res & Dev, Zug, Switzerland.
    Kiladjian, Jean-Jacques
    St Louis Hosp, APHP, Clin Invest Ctr, Paris, France.
    Harrison, Claire N.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England.
    Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study2018In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 74, p. 105-109Article in journal (Refereed)
    Abstract [en]

    EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both. Standard incidence ratios (SIRs) were calculated using data from the Cancer Incidence in Five Continents database to account for differences in age-, gender-, and country-specific background rates. SIRs for acute myelogenous leukemia (AML) were high in ET patients. SIRs for AML were high in HC-treated patients, but AML was rare in ANA-treated patients; no cases of AML were found in patients only treated with ANA. No statistically significant difference was seen between SIRs for ANA and HC treatment for AML or skin cancer. SIRs for other cancers were similar in the HC and ANA groups and close to 1, indicating little difference in risk. Although statistically inconclusive, this study strengthens concerns regarding possible leukemogenic risk with HC treatment. (NCT00202644)

  • 12.
    Birgegård, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Folkvaljon, Yasin
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden.
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, London, England.
    Besses, C.
    Hosp Mar IMIM, Dept Haematol, Barcelona, Spain.
    Griesshammer, M.
    Johannes Wesling Med Ctr, Hematol & Oncol, Minden, Germany.
    Gugliotta, L.
    St Orsola Malpighi Hosp, Dept Haematol, Bologna, Italy.
    Wu, J.
    Shire Pharmaceut, Global Biometr, Lexington, MA USA.
    Achenbach, H.
    Shire GmBH, Res & Dev, Zug, Switzerland.
    Kiladjian, J. -J
    Harrison, C. N.
    Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England.
    LEUKEMIC TRANSFORMATION AND SECOND CANCERS IN 3649 HIGH RISK ET PATIENTS IN THE EXELS STUDY2017In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no Suppl. 2, p. 282-282, article id P704Article in journal (Other academic)
  • 13.
    Bratt, Ola
    et al.
    Lund Univ, Div Urol Canc, Dept Translat Med Urol, Lund, Sweden.;Cambridge Univ Hosp, CamPARI Clin, Dept Urol, Cambridge, England..
    Drevin, Linda
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Akre, Olof
    Karolinska Inst, Dept Urol, Stockholm, Sweden..
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Family History and Probability of Prostate Cancer, Differentiated by Risk Category: A Nationwide Population-Based Study2016In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, no 10, article id djw110Article in journal (Refereed)
    Abstract [en]

    Background: Familial prostate cancer risk estimates are inflated by clinically insignificant low-risk cancer, diagnosed after prostate-specific antigen testing. We provide age-specific probabilities of non-low-and high-risk prostate cancer. Methods: Fifty-one thousand, eight hundred ninety-seven brothers of 32 807 men with prostate cancer were identified in Prostate Cancer data Base Sweden (PCBaSe). Nelson-Aalen estimates with 95% confidence intervals (CIs) were calculated for cumulative, family history-stratified probabilities of any, non-low-(any of Gleason score >= 7, prostate-specific antigen [PSA] >= 10 ng/mL, T3-4, N1, and/or M1) and high-risk prostate cancer (Gleason score >= 8 and/or T3-4 and/or PSA >= 20 ng/mL and/or N1 and/or M1). Results: The population probability of any prostate cancer was 4.8% (95% CI = 4.8% to 4.9%) at age 65 years and 12.9% (95% CI = 12.8% to 12.9%) at age 75 years, of non-low-risk prostate cancer 2.8% (95% CI = 2.7% to 2.8%) at age 65 years and 8.9% (95% CI = 8.8% to 8.9%) at age 75 years, and of high-risk prostate cancer 1.4% (95% CI = 1.3% to 1.4%) at age 65 years and 5.2% (95% CI = 5.1% to 5.2%) at age 75 years. For men with one affected brother, probabilities of any prostate cancer were 14.9% (95% CI = 14.1% to 15.8%) at age 65 years and 30.3% (95% CI = 29.3% to 31.3%) at age 75 years, of non-low-risk prostate cancer 7.3% (95% CI = 6.7% to 7.9%) at age 65 years and 18.8% (95% CI = 17.9% to 19.6%) at age 75 years, and of high-risk prostate cancer 3.0% (95% CI = 2.6% to 3.4%) at age 65 years and 8.9% (95% CI = 8.2% to 9.5%) at age 75 years. Probabilities were higher for men with a stronger family history. For example, men with two affected brothers had a 13.6% (95% CI = 9.9% to 17.6 %) probability of high-risk cancer at age 75 years. Conclusions: The age-specific probabilities of non-low-and high-risk cancer presented here are more informative than relative risks of any prostate cancer and more suitable to use for counseling men with a family history of prostate cancer.

  • 14. Carlhed, Rickard
    et al.
    Bojestig, Mats
    Peterson, Anette
    Åberg, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Improved clinical outcome after acute myocardial infarction in hospitals participating in a Swedish quality improvement initiative2009In: Circulation. Cardiovascular quality and outcomes, ISSN 1941-7713, Vol. 2, no 5, p. 458-464Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Swedish quality improvement initiative Quality Improvement in Coronary Care previously demonstrated significant improvements in caregiver adherence to national guidelines for acute myocardial infarction. The associated impact on 1-year clinical outcome is presented here. METHODS AND RESULTS: During the baseline period July 2001 to June 2002, 6878 consecutive acute myocardial infarction patients <80 years were included at the 19 intervention and 19 control hospitals and followed for a mean of 12 months. During the postintervention period of May 2003 to April 2004, 6484 patients were included and followed in the same way. From baseline to postintervention, improvements in mortality and cardiovascular readmission rates (events per 100 patient-years) were significant in the intervention group (-2.82, 95% CI -5.26 to -0.39; -9.31, 95% CI -15.48 to -3.14, respectively). However, in the control hospitals, there were no significant improvements (0.04, 95% CI -2.40 to 2.47; -4.93, 95% CI -11.10 to 1.24, respectively). Bleedings in the control group increased in incidence (0.92, 95% CI 0.41 to 1.43), whereas the incidence remained unchanged in the intervention group (0.07, 95% CI -0.44 to 0.58). When the difference of changes between the study groups were evaluated, the results still were in favor of the intervention group, albeit significant only for bleeding complications (mortality: -2.70, 95% CI -6.37 to 0.97; cardiovascular readmissions: -6.85, 95% CI -16.62 to 2.93; bleeding complications: -0.82, 95% CI -1.66 to 0.01). CONCLUSIONS: With a systematic quality improvement initiative aiming to increase the adherence to acute myocardial infarction guidelines, it is possible to achieve long-term positive effects on clinical outcome.

  • 15.
    Cazzaniga, Walter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. IRCCS Osped San Raffaele, Unit Urol URI, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden;Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, no 3, p. 421-428Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s.

    PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR.

    RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47).

    CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

  • 16.
    Crawley, Danielle
    et al.
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Garmo, Hans
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust, London, England.;Kings Coll Londons Comprehens, Biomed Res Ctr, London, England..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Häggström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Zethelius, Björn
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Holmberg, Lars
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Adolfsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 139, no 12, p. 2698-2704Article in journal (Refereed)
    Abstract [en]

    Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti-androgens (AA), orchiectomy, or gonadotropin-releasing hormone (GnRH) agonists compared to an age-matched, PCa-free comparison cohort (n=167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 121.5 years HR: 1.61 (95% CI: 1.36-1.91)], compared to PCa-free men. The risk decreased thereafter (e.g., 324 years HR: 1.17 (95% CI: 0.98-1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95% CI: 0.65-0.84). The incidence of T2DM per 1,000 person-years was 10 for PCa-free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.

  • 17.
    Eriksson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Res Oncol, Canc Epidemiol Grp, Div Canc Studies, London, England..
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ihre-Lundgren, Catharina
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    The Influence of Preoperative Symptoms on the Death of Patients with Small Intestinal Neuroendocrine Tumors2017In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 24, no 5, p. 1214-1220Article in journal (Refereed)
    Abstract [en]

    Small intestinal neuroendocrine tumors (SI-NETs) are uncommon tumors with an annual incidence of about 1 per 100,000. Usually, SI-NETs have a slow progression, and patients often present with generalized disease. Many patients do well, and the disease has a relatively favorable 5-year survival rate. Some SI-NETs, however, have a more negative prognosis. This study aimed to establish prognostic factors for death identifiable at primary surgery. A nested case-control study investigated 1150 patients from the cohort of all patients with a diagnosis of SI-NETs in Sweden between 1961 and 2001. The study cases consisted of all patients who died of SI-NETs during the study period. Each case was assigned a control subject matched by age at diagnosis and calendar period. Possible prognostic factors [gender, degree of symptoms, indication for surgery, World Health Organization (WHO) stage] were evaluated in uni- and multivariable analyses. The patients with symptomatic disease had an increased risk of dying. The indication for primary surgery influenced survival, showing a more negative prognosis for elective surgery. The WHO stage influenced survival, and stage 4 patients had an almost threefold risk of dying compared with stages 1 to 3b patients. This study showed that preoperative symptoms are important in prognostication for SI-NETs. Hormonal symptoms generally signify a patient with a more advanced disease stage and a worse prognosis. Including symptomatic disease together with the WHO stage and grade could possibly increase the accuracy of prognostication.

  • 18.
    Eriksson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ihre-Lundgren, Catharina
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Prognostic factors for death after surgery for small intestinal neuroendocrine tumoursIn: Article in journal (Refereed)
  • 19.
    Eriksson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ihre-Lundgren, Catharina
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Symptomatic disease at the time of surgery have prognostic impact in small intestinal neuroendocrine tumoursIn: British Journal of Surgery OpenArticle in journal (Refereed)
  • 20.
    Eriksson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Juhlin, Christofer
    Backman, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Edfeldt, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ihre-Lundgren, Catharina
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    TFF3 in primary tumours has a negative impact on survival in small intestinal neuroendocrine tumoursIn: Article in journal (Refereed)
  • 21.
    Eriksson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ögren, Mats
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ihre-Lundgren, Catharina
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Primary small intestinal tumours are highly prevalent and often multiple before metastatic disease developsIn: Article in journal (Refereed)
  • 22.
    Essen, Anneli
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Sci, Guys Hosp, Res Oncol Translat Oncol & Urol Res TOUR, 3rd Floor,Bermondsey Wing, London SE1 9RT, England.
    Santaolalla, Aida
    Kings Coll London, Sch Canc & Pharmaceut Sci, Guys Hosp, Res Oncol Translat Oncol & Urol Res TOUR, 3rd Floor,Bermondsey Wing, London SE1 9RT, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, Guys Hosp, Res Oncol Translat Oncol & Urol Res TOUR, 3rd Floor,Bermondsey Wing, London SE1 9RT, England;Reg Canc Ctr, Uppsala, Sweden.
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;AstraZeneca, Global Med Affairs, Med Evidence & Observat Res, Molndal, Sweden.
    Walldius, Göran
    Karolinska Inst, Inst Environm Med, Dept Cardiovasc Epidemiol, Stockholm, Sweden.
    Jungner, Ingmar
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden;CALAB Res, Stockholm, Sweden.
    Malmström, Håkan
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum AB, Biostat Res & Dev, Stockholm, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Sci, Guys Hosp, Res Oncol Translat Oncol & Urol Res TOUR, 3rd Floor,Bermondsey Wing, London SE1 9RT, England.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, Guys Hosp, Res Oncol Translat Oncol & Urol Res TOUR, 3rd Floor,Bermondsey Wing, London SE1 9RT, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Baseline serum folate, vitamin B12 and the risk of prostate and breast cancer using data from the Swedish AMORIS cohort2019In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 30, no 6, p. 603-615Article in journal (Refereed)
    Abstract [en]

    Purpose: The roles of folate and vitamin B12 in prostate cancer (PCa) or breast cancer (BC) development are unclear. We investigated their roles using the prospective Swedish Apolipoprotein MOrtality RISk (AMORIS) study.

    Methods: 8,783 men and 19,775 women with vitamin B12 and folate serum measurements were included. Their associations with PCa and BC risk categories were evaluated using Cox proportional hazards regression.

    Results: During mean follow-up of 13years, 703 men developed PCa. There was an inverse association between folate>32nmol/L and high-risk PCa [hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02-0.90], and a positive association between folate<5nmol/L and metastatic PCa (HR 5.25, 95% CI 1.29-21.41), compared with folate 5-32nmol/L. No associations with vitamin B12 were found. 795 women developed BC during mean follow-up of 14years. When restricting to the fasting population, there was a positive association between folate>32nmol/L and BC (HR 1.47, 95% CI 1.06-2.04).

    Conclusion: High folate levels may protect against PCa and low folate levels may increase risk of metastatic PCa. High fasting folate levels may be associated with an increased BC risk. Vitamin B12 was not found to be linked with risk of PCa or BC. Longitudinal studies with serum and dietary information could help define new prevention targets and add information on the role of folate fortification.

  • 23. Fredholm, H.
    et al.
    Magnusson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lindstrom, L. S.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eaker, Sonja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Bergh, J.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Frisell, J.
    Fredriksson, I.
    Breast cancer in young women - age a risk factor only in those not given chemotherapy2014In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 23, no S1, p. S12-S12, article id HM31Article in journal (Other academic)
  • 24. Gaur, Anjali
    et al.
    Collins, Helen
    Wulaningsih, Wahyu
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hammar, Niklas
    Walldius, Goran
    Jungner, Ingmar
    Van Hemelrijck, Mieke
    Iron metabolism and risk of cancer in the Swedish AMORIS study2013In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 24, no 7, p. 1393-1402Article in journal (Refereed)
    Abstract [en]

    Pre-clinical studies have shown that iron can be carcinogenic, but few population-based studies investigated the association between markers of the iron metabolism and risk of cancer while taking into account inflammation. We assessed the link between serum iron (SI), total-iron binding capacity (TIBC), and risk of cancer by levels of C-reactive protein (CRP) in a large population-based study (n = 220,642). From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected all participants (> 20 years old) with baseline measurements of serum SI, TIBC, and CRP. Multivariate Cox proportional hazards regression was carried out for standardized and quartile values of SI and TIBC. Similar analyses were performed for specific cancers (pancreatic, colon, liver, respiratory, kidney, prostate, stomach, and breast cancer). To avoid reverse causation, we excluded those with follow-up < 3 years. We found a positive association between standardized TIBC and overall cancer [HR 1.03 (95 % CI 1.01-1.05)]. No statistically significant association was found between SI and cancer risk except for postmenopausal breast cancer [HR for standardized SI 1.09 (95 % CI 1.02-1.15)]. The association between TIBC and specific cancer was only statistically significant for colon cancer [i.e., HR for standardized TIBC: 1.17 (95 % CI 1.08-1.28)]. A borderline interaction between SI and levels of CRP was observed only in stomach cancer. As opposed to pre-clinical findings for serum iron and cancer, this population-based epidemiological study showed an inverse relation between iron metabolism and cancer risk. Minimal role of inflammatory markers observed warrants further study focusing on developments of specific cancers.

  • 25.
    Ghoshal, Arunangshu
    et al.
    Kings Coll London, Div Canc Studies Translat Oncol & Urol Res, London SE1 9RT, England.;Tata Mem Hosp, Dept Palliat Med, Bombay 400012, Maharashtra, India..
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Kings Coll London, Div Canc Studies Translat Oncol & Urol Res, London SE1 9RT, England.
    Arthur, Rhonda
    Kings Coll London, Div Canc Studies Translat Oncol & Urol Res, London SE1 9RT, England..
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, SE-17177 Stockholm, Sweden.;AstraZeneca R & D, S-43150 Molndal, Sweden..
    Jungner, Ingmar
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, SE-17177 Stockholm, Sweden.;CALAB Res, SE-17177 Stockholm, Sweden..
    Malmström, Håkan
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Lambe, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Walldius, Göran
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, SE-17177 Stockholm, Sweden..
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies Translat Oncol & Urol Res, London SE1 9RT, England.;Karolinska Inst, Inst Environm Med, Unit Epidemiol, SE-17177 Stockholm, Sweden..
    Serum biomarkers to predict risk of testicular and penile cancer in AMORIS2017In: ecancermedicalscience, ISSN 1754-6605, E-ISSN 1754-6605, Vol. 11, article id 762Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the association between commonly measured serum biomarkers of inflammation and penile and testicular cancer risk in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study.

    Materials and methods: A total of 205,717 subjects had baseline measurements of C-reactive protein, albumin, and haptoglobin. The association between quartiles and dichotomised values of inflammatory markers and penile and testicular cancer risk were analysed by using multivariate Cox proportional hazard models.

    Results: A total of 125 men were diagnosed with testicular cancer and 50 with penile cancer during a mean follow-up of 20.3 years. No statistically significant trends were seen between serum inflammatory markers and risk of penile cancer, but higher albumin levels increased the risk of testicular cancer [HR for albumin (g/L): 1.10 (95% CI: 1.03-1.18)]. However, this trend was not observed when using medical cut-offs of albumin.

    Conclusions: In the present study, we did not find support for an association between commonly used markers of inflammation and risk of testicular or penile cancer. The role of inflammation may be more complicated and require assessment of more specialised measurements of inflammation in future studies.

  • 26.
    Ghoshal, Arunangshu
    et al.
    King's Coll London, Translat Oncol & Urol Res, Sch Canc & Pharmaceut Sci, Guys Hosp, 3rd Floor,Bermondsey Wing, London SE1 9RT, England;Tata Mem Hosp, Dept Palliat Med, Bombay 40012, Maharashtra, India.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. King's Coll London, Translat Oncol & Urol Res, Sch Canc & Pharmaceut Sci, Guys Hosp, 3rd Floor,Bermondsey Wing, London SE1 9RT, England.
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, SE-17177 Stockholm, Sweden;AstraZeneca R&D, S-43150 Molndal, Sweden.
    Jungner, Ingmar
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, SE-17177 Stockholm, Sweden;CALAB Res, SE-17177 Stockholm, Sweden.
    Malmström, Håkan
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, SE-17177 Stockholm, Sweden;CALAB Res, SE-17177 Stockholm, Sweden;Swedish Orphan Biovitrum AB, Biostat Res & Dev, SE-11276 Stockholm, Sweden.
    Walldius, Göran
    Karolinska Inst, Cardiovasc Epidemiol Unit, Inst Environm Med, SE-17177 Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kingss Coll London, Translat Oncol & Urol Res, Sch Canc & Pharmaceut Sci, Guys Hosp, 3rd Floor,Bermondsey Wing, London SE1 9RT, England;Karolinska Inst, Inst Environm Med, Epidemiol Unit, SE-17177 Stockholm, Sweden.
    Can pre-diagnostic serum levels of sodium and potassium predict prostate cancer survival?2018In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 18, article id 1169Article in journal (Refereed)
    Abstract [en]

    There is evidence that derangement in serum electrolytes like sodium and potassium is associated with increased morbidity and mortality among hospitalized critically ill patients, but their role in the context of cancer survival remains poorly understood. We sought to investigate the association of pre-diagnostic serum sodium and potassium with risk of overall, cancer-specific, and cardiovascular (CV) death among 11,492 men diagnosed with prostate cancer (PCa) from the Swedish AMORIS study. Multivariable Cox proportional hazards regression was used to assess the risk of death by clinical categories of pre-diagnostic serum sodium and potassium. During a mean follow-up of 5.7years, 1649 men died of PCa. Serum levels of sodium were not indicative of PCa-specific or CV death. A weak positive association was found between pre-diagnostic higher serum potassium (>5mEq/L) and overall death [HR: 1.26 (95% CI: 1.01-1.59)] as compared to low/normal levels of clinical cut-offs. The current study did not find strong evidence for a role of electrolytes in PCa mortality. To further disentangle the potential role of electrolytes in cancer development, future studies should use repeated measurement of serum electrolytes. This research project was reviewed and approved by the Stockholm Ethical Committee (Dnr 2010/1:7).

  • 27.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Sørbye, H
    Balteskard, L
    Byström, P
    Pfeiffer, P
    Tveit, K
    Heikkilä, R
    Keldsen, N
    Albertsson, M
    Starkhammar, H
    Garmo, H
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, no 5, p. 909-914Article in journal (Refereed)
    Abstract [en]

    Background: To compare irinotecan with the Nordic 5- fluorouracil (5- FU) and folinic acid (FA) bolus schedule [ irinotecan 180 mg/m(2) on day 1, 5- FU 500 mg/m(2) and FA 60 mg/m(2) on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [ irinotecan 180 mg/m(2) on day 1, FA 200 mg/m(2), 5- FU bolus 400 mg/m(2) and infused 5- FU 600 mg/m(2) on day 1 and 2 (Lv5FU2- IRI)] due to uncertainties about how to administrate 5- FU with irinotecan.

    Patients and methods: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2- IRI. Primary end point was progression- free survival (PFS).

    Results: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60- day mortality was 2.4% versus 2.1%.

    Conclusions: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated.

  • 28.
    Grundmark, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Loda, Massimo
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The Metabolic Syndrome and the Risk of Prostate Cancer under Competing Risks of Death from Other Causes2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 8, p. 2088-2096Article in journal (Refereed)
    Abstract [en]

    Background:

    Associations between metabolic syndrome (MetS) components and prostate cancer development have not been studied comprehensively; results have been divergent. Using the National Cholesterol Education Program Adult Treatment panel III (NCEP) and International Diabetes Federation (IDF) definitions of the MetS, we investigated such associations taking competing risks of death into consideration.

    Methods:

    In the prospective Uppsala Longitudinal Study of Adult Men of 2,322 Caucasian men with 34 years of follow-up baseline, MetS measurements at age 50 years were used. Cumulative incidence of prostate cancer and death with/without the MetS were calculated. Competing risk of dying was taken into account by calculating the conditional probability of prostate cancer with/without the MetS.

    Results:

    Two hundred and thirty-seven prostate cancers were identified. Prostate cancer probability by age 80 years with baseline MetS compared with without MetS was nonsignificantly higher [5.2 percent units (confidence interval (CI), -0.8% to 11.3%; NCEP); 2.7 percent units (CI, -2.7% to 8.0%; IDF)]; cumulative incidence proportions of death was significantly higher [19.3 percent units (CI, 13.4-25.3%; NCEP); 15.3 percent units (CI, 9.5-21.1%; IDF)]; and conditional probability of prostate cancer considering death from other causes was significantly higher [7.3 percent-units (CI, 0.2-14.5%); odds ratio of 1.64 (CI, 1.03-2.23; NCEP)] and nonsignificantly higher [5.0 percent-units (CI, -1.6% to 11.6%); odds ratio of 1.43 (CI, 0.89-1.90; IDF].

    Conclusions:

    The MetS by the NCEP definition is associated with prostate cancer, taking the competing risk of early death from other causes into account. Impact: The results further highlight the public health effect of the increasing prevalence of MetS and the importance of considering competing risks when studying risk factors for cancer.

  • 29.
    Grundmark, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Stattin, P
    Lambe, M
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Anti-androgen prescribing patterns, patient treatment adherence and influencing factors: results from the nationwide PCBaSe Sweden2012In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 68, no 12, p. 1619-1630Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Adherence has not been studied in male oncology populations. The aim of this study on both the prescriber and user perspectives in prostate cancer treatment was to analyse real-life prescribing patterns of anti-androgens (AA), primarily bicalutamide, and factors influencing the patients' adherence to treatment.

    METHODS:

    A nationwide clinical cohort of incident prostate cancer, PCBaSe, was linked to the Swedish Prescribed Drug Register. Men with a planned first line monotherapy AA treatment were identified; dosages and extent of off-label treatment were investigated. Cumulative incidence proportions for reasons for drug discontinuation were calculated. Factors potentially influencing adherence were explored using the medical possession ratio based on the individual prescribed daily dose.

    RESULTS:

    First line monotherapy AA was planned in 4.4 % of all incident cases and in 2.1 % of low risk disease cases. Among 1,406 men prescribed bicalutamide, 1,109 (79 %) received the approved daily dose of 150 mg. Discontinuation reasons differed with disease severity. Off-label, low-dose prescription associated with age above 75 years and disease categorised as low risk was noted in 297 men (21 %). Sixty percent of the men adhered well, i.e. to ≥80 %. Age above 75 years and less severe disease were both negatively associated with adherence.

    CONCLUSIONS:

    Patient age and tumour risk group influenced the prescriber's choice of dose, pointing to important issues for critical reflection. Possible over-treatment was noted in low risk disease. Interventions to increase adherence in older men and in men with less severe disease are worth considering after critically reviewing the appropriateness of the treatment indication, especially in the latter case.

  • 30.
    Grundmark, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up2011In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 11, p. 431-Article in journal (Refereed)
    Abstract [en]

    Background: Serum selenium level (s-Se) has been associated with prostate cancer (PrCa) risk. We investigated the relation between s-Se, smoking and non-screening detected PrCa and explored if polymorphisms in two DNA repair genes: OGG1 and MnSOD, influenced any effect of s-Se.

    Methods: ULSAM, a population based Swedish male cohort (n = 2322) investigated at age 50 for s-Se and s-Se influencing factors: serum cholesterol, erythrocyte sedimentation rate and smoking habits. At age 71 a subcohort, (n = 1005) was genotyped for OGG1 and MnSOD polymorphisms.

    Results: In a 34-year-follow-up, national registries identified 208 PrCa cases further confirmed in medical records. Participants with s-Se in the upper tertile had a non-significantly lower risk of PrCa. Smokers with s-Se in the two lower tertiles (<= 80 mu g/L) experienced a higher cumulative incidence of PrCa than smokers in the high selenium tertile (Hazard Ratio 2.39; 95% CI: 1.09-5.25). A high tertile selenium level in combination with non-wt rs125701 of the OGG1 gene in combination with smoking status or rs4880 related variation of MnSOD gene appeared to protect from PrCa.

    Conclusions: S-Se levels and smoking habits influence long-term risk of PrCa. Smoking as a risk factor for PrCa in men with low s-Se is relevant to explore further. Exploratory analyses of variations in OGG1 and MnSOD genes indicate that hypotheses about patterns of exposure to selenium and smoking combined with data on genetic variation in genes involved in DNA repair can be valuable to pursue.

  • 31.
    Häggström, Christel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Stocks, Tanja
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Lund, Sweden..
    Garmo, Hans
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.;Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England..
    Holmberg, Lars
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.;Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England..
    Van Hemelrijck, Mieke
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Interpretation of conventional survival analysis and competing-risk analysis: an example of hypertension and prostate cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 6, p. 850-852Article in journal (Other academic)
  • 32.
    Häggström, Christel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden;Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Rowley, Mark
    Kings Coll London, Inst Math & Mol Biomed, London, England;Saddle Point Sci, London, England.
    Coolen, Anthony C. C.
    Kings Coll London, Inst Math & Mol Biomed, London, England.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and Type 2 diabetes mellitus2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 8, p. 1868-1875Article in journal (Refereed)
    Abstract [en]

    Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of our study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between Type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow-up of 6years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment.

  • 33.
    Lambe, Mats
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; Regional Oncologic Centre, Uppsala, Sweden .
    Wigertz, Annette
    Regional Oncologic Centre, Uppsala, Sweden .
    Garmo, Hans
    Regional Oncologic Centre, Uppsala, Sweden .
    Walldius, Göran
    Department of Medicine, and Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Jungner, Ingmar
    Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet and CALAB Research, Stockholm, Sweden.
    Hammar, Niklas
    Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; AstraZeneca R&D, Södertälje, Sweden .
    Impaired glucose metabolism and diabetes and the risk of breast, endometrial, and ovarian cancer2011In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 22, no 8, p. 1163-1171Article in journal (Refereed)
    Abstract [en]

    Background

    Epidemiological evidence indicates that individuals with type 2 diabetes are at an increased risk of cancer. Elevated glucose levels, below the diagnostic threshold for diabetes, have also been suggested to be associated with increased cancer risks.

    Methods

    We investigated possible associations between glucose levels and the risk of breast, endometrial, and ovarian cancer in a cohort of more than 230,000 women, for which information on outcome and potential confounders was obtained by record linkage to population-based registers.

    Results

    Diabetes was associated with an increased risk of postmenopausal breast cancer (HR = 1.22, 95% CI 1.04–1.43). An indication of a slightly elevated breast cancer risk was also found in postmenopausal women with impaired glucose metabolism (HR = 1.11, 95% CI 0.96–1.28). Diabetes (HR = 1.46, 95% CI 1.09–1.96) and impaired glucose metabolism (HR = 1.41, 95% CI 1.08–1.85) were associated with an increased risk of endometrial cancer. No associations were found between glucose levels and ovarian cancer risk. Following adjustment for BMI, estimates were attenuated for endometrial cancer, while point estimates for breast and ovarian cancer remained essentially unchanged.

    Conclusions

    Our results indicate that glucose levels below the diagnostic threshold for diabetes modify the risk not only of endometrial cancer but possibly also of postmenopausal breast cancer.

  • 34.
    Lindhagen, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Med, Canc Epidemiol Grp, Div Canc Studies,Res Oncol,Guys Hosp, London SE1 9RT, England.;Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Sch Med, Canc Epidemiol Grp, Div Canc Studies,Res Oncol,Guys Hosp, London SE1 9RT, England.
    How to model temporal changes in comorbidity for cancer patients using prospective cohort data2015In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 15, article id 96Article in journal (Refereed)
    Abstract [en]

    Background: The presence of comorbid conditions is strongly related to survival and also affects treatment choices in cancer patients. This comorbidity is often quantified by the Charlson Comorbidity Index (CCI) using specific weights (1, 2, 3, or 6) for different comorbidities. It has been shown that the CCI increases at different times and with different sizes, so that traditional time to event analysis is not adequate to assess these temporal changes. Here, we present a method to model temporal changes in CCI in cancer patients using data from PCBaSe Sweden, a nation-wide population-based prospective cohort of men diagnosed with prostate cancer. Our proposed model is based on the assumption that a change in comorbidity, as quantified by the CCI, is an irreversible one-way process, i.e., CCI accumulates over time and cannot decrease. Methods: CCI was calculated based on 17 disease categories, which were defined using ICD-codes for discharge diagnoses in the National Patient Register. A state transition model in discrete time steps (i.e., four weeks) was applied to capture all changes in CCI. The transition probabilities were estimated from three modelling steps: 1) Logistic regression model for vital status, 2) Logistic regression model to define any changes in CCI, and 3) Poisson regression model to determine the size of CCI change, with an additional logistic regression model for CCI changes >= 6. The four models combined yielded parameter estimates to calculate changes in CCI with their confidence intervals. Results: These methods were applied to men with low-risk prostate cancer who received active surveillance (AS), radical prostatectomy (RP), or curative radiotherapy (RT) as primary treatment. There were large differences in CCI changes according to treatment. Conclusions: Our method to model temporal changes in CCI efficiently captures changes in comorbidity over time with a small number of regression analyses to perform - which would be impossible with tradition time to event analyses. However, our approach involves a simulation step that is not yet included in standard statistical software packages. In our prostate cancer example we showed that there are large differences in development of comorbidities among men receiving different treatments for prostate cancer.

  • 35. Lissbrant, Ingela Franck
    et al.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Widmark, Anders
    Stattin, Par
    Population-based study on use of chemotherapy in men with castration resistant prostate cancer2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 8, p. 1593-1601Article in journal (Refereed)
    Abstract [en]

    Background. Chemotherapy prolongs life and relieves symptoms in men with castration resistant prostate cancer (CRPC). There is limited information on a population level on the use of chemotherapy for CRPC. Material and methods. To assess the use of chemotherapy in men with CRPC we conducted a register-based nationwide population-based study in Prostate Cancer data Base Sweden (PCBaSe) and a nationwide in-patient drug register (SALT database) between May 2009 and December 2010. We assumed that men who died of prostate cancer (PCa) underwent a period of CRPC before they died. Results. Among the 2677 men who died from PCa during the study inclusion period, 556 (21%) had received chemotherapy (intravenous or per oral) detectable within the observation period in SALT database. Specifically, 239 (61%) of men <70 years had received chemotherapy, 246 (30%) of men between 70 and 79 years and 71 (5%) men older than 80 years. The majority of men 465/556 (84%) had received a docetaxel-containing regimen. Among chemotherapy treated men, 283/556 (51%) received their last dose of chemotherapy during the last six months prior to death. Treatment with chemotherapy was more common among men with little comorbidity and high educational level, as well as in men who had received curatively intended primary treatment. Conclusion. A majority of men younger than 70 years with CRPC were treated with chemotherapy in contrast to men between 70 and 79 years of whom half as many received chemotherapy. Chemotherapy treatment was often administered shortly prior to death. The low uptake of chemotherapy in older men with CRPC may be caused by concerns about tolerability of treatment, as well as treatment decisions based on chronological age rather than global health status.

  • 36. Lundstrom, Karl-Johan
    et al.
    Drevin, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carlsson, Stefan
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Loeb, Stacy
    Stattin, Par
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Nationwide Population Based Study of Infections after Transrectal Ultrasound Guided Prostate Biopsy2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 4, p. 1116-1122Article in journal (Refereed)
    Abstract [en]

    Purpose: Transrectal ultrasound guided biopsy is the gold standard for detecting prostate cancer but international reports suggest that increasing risks are associated with the procedure. We estimated incidence and risk factors for infection after prostate biopsy as well as 90-day mortality using a nationwide Swedish sample.

    Material and Methods: We performed a population based study of 51,321 men from PCBaSe between 2006 and 2011. Primary outcome measures were dispensed prescriptions of antibiotics for urinary tract infection and hospitalization with a discharge diagnosis of urinary tract infection. Multivariable logistic regression was used to examine risk factors for infection in men who underwent prostate biopsy.

    Results: During the 6 months before biopsy the background incidence of urinary tract infection was approximately 2%. Within 30 days after biopsy 6% of the men had a dispensed prescription for urinary tract antibiotics and 1% were hospitalized with infection. The strongest risk factors for an antibiotic prescription were prior infection (OR 1.59, 95% CI 1.45-1.73), high Charlson comorbidity index (OR 1.25, 95% CI 1.11-1.41) and diabetes (OR 1.32, 95% CI 1.17-1.49). Risk of an antibiotic prescription after biopsy decreased from 2006 to 2011 (OR 0.79, 95% CI 0.70-0.90) but the risk of hospital admission increased (OR 2.14, 95% CI 1.58-2.94). No significant increase was observed in 90-day mortality.

    Conclusions: Severe infections with hospitalization after prostate biopsy are increasing in Sweden. The risk of post-biopsy infection is highest in men with a history of urinary tract infection and those with significant comorbidities.

  • 37.
    Lycken, Magdalena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Drevin, Linda
    Reg Canc Ctr, Uppsala, Sweden..
    Garmo, Hans
    Reg Canc Ctr, Uppsala, Sweden.;Kings Coll London, Sch Med, Div Canc Studies, London, England..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.;Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA.;Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Lissbrant, Ingela Franck
    Sahlgrens Acad, Inst Clin Sci, Dept Oncol, Gothenburg, Sweden..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Reg Canc Ctr, Uppsala, Sweden.;Kings Coll London, Sch Med, Div Canc Studies, London, England..
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden..
    Use of palliative medications before death from prostate cancer: a population based study2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no SI 220, p. 25-26Article in journal (Other academic)
  • 38.
    Lycken, Magdalena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Adolfsson, Jan
    Stattin, Par
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Patterns of androgen deprivation therapies among men diagnosed with localised prostate cancer: A population-based study2014In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, no 10, p. 1789-1798Article in journal (Refereed)
    Abstract [en]

    Aim: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. Methods and materials: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1-2, N0-NX, M0-MX and prostate specific antigen (PSA) <50 ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. Results: The cumulative incidence of castration at 10 years after diagnosis was 11.6% (95% confidence interval (CI), 11.0-12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2-11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4 years in the deferred treatment high-risk group to 17 years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. Conclusion: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment. 

  • 39. Melvin, J. C.
    et al.
    Rodrigues, C.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hammar, N.
    Jungner, I.
    Walldius, G.
    Lambe, Mats
    Regional Oncologic Centre, Uppsala Sweden.
    Jassem, W.
    Van Hemelrijck, M.
    Gamma-glutamyl transferase and c-reactive protein as alternative markers of metabolic abnormalities and their associated comorbidites: A prospective cohort study2012In: International Journal of Molecular Epidemiology and Genetics, ISSN 1948-1756, Vol. 3, no 4, p. 276-285Article in journal (Refereed)
    Abstract [en]

    Background: Recent studies suggested that gamma-glutamyl transferase (GGT) and C-reactive protein (CRP) are good markers of metabolic abnormalities. We assessed the link between GGT, CRP and common metabolic abnormalities, as well their link to related diseases, such as cancer and cardiovascular disease (CVD). Methods: We selected 333,313 subjects with baseline measurements of triglycerides (TG), total cholesterol (TC), glucose, GGT and CRP in the Swedish AMORIS study. Baseline measurement of BMI was available for 63,900 persons and 77,944 had baseline measurements of HDL. Pearson correlation coefficients between CRP, GGT, and metabolic components (TG, HDL, BMI and TC) were calculated. To investigate the combined effect of GGT and CRP we created a score ranging from 0 to 6 and used Cox proportional hazard models to evaluate its association with CVD and cancer. Results: 21,216 individuals developed cancer and 47,939 CVD. GGT and TG had the strongest correlation (r=0.22). An increased risk of cancer was identified with elevated levels of GGT or CRP or both markers (GGT-CRP score ≥3); the greatest risk of cancer was found when GGT-CRP score = 6 (HR: 1.40 (95%CI: 1.31-1.48) and 1.60 (1.47-1.76) compared to GGT-CRP score = 0, respectively). Conclusion: While GGT and CRP have been shown to be associated with metabolic abnormalities previously, their association to the components investigated in this study was limited. Results did demonstrate that these markers were predictive of associated diseases, such as cancer.

  • 40. Melvin, Jennifer C
    et al.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Daniel, Rhian
    Shanmugalingam, Thurkaa
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Häggström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rudman, Sarah
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Van Hemelrijck, Mieke
    An investigation into the relationship between Statins and Cancer using population-based data2015In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 116, no 5, p. 681-683Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Results to date for the association between use of statins and prostate cancer (PCa) death in observational studies are inconsistent. We investigated the application of causal inference methods, which aim to address observational data as if they were from a randomised clinical trial (RCT).

    MATERIAL AND METHODS: We examined the association between statins and PCa-death in 14,926 men in PCBaSe Sweden. We used inverse probability weighted (IPW) estimation of marginal structural models (MSM), as well incorporating truncated IPW in the presence of time-dependent confounders (TDC) (e.g., disease severity), affected by the exposure.

    RESULTS: The baseline adjusted odds ratio (OR) was 0.62 (95%CI: 0.51-0.75), which compared risk of PCa-death between men on statins and men not on statins. The calculated IPW for the MSM were highly variable, with the smallest weight at 0.0019 and the largest at 13,574, resulting in an OR of 0.89 (95%CI: 0.69-1.14). Truncating the weights improved variability, reducing the largest weight to 13.16. The truncated MSM OR was 0.86 (95%CI: 0.81-0.91).

    CONCLUSION: An association of statins and risk of PCa-death could not be reliably discerned, due to lack of data on essential confounders, namely serum cholesterol levels and disease severity. No observational studies on statin-use to date present information on serum cholesterol levels and disease severity in one setting, highlighting the need for careful interpretation of investigations into drugs in relation to diseases other than their intended purpose in observational settings.

  • 41.
    Michaëlsson, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nordström, Peter
    Nordström, Anna
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pedersen, Nancy L
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Impact of hip fracture on mortality: a cohort study in hip fracture discordant identical twins2014In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, no 2, p. 424-431Article in journal (Refereed)
    Abstract [en]

    Several studies have shown a long-lasting higher mortality after hip fracture but the reasons of the excess risk is not well understood. We aimed to determine whether there exists a higher mortality after hip fracture when controlling for genetic constitution, shared environment, comorbidity and lifestyle by use of a nation-wide cohort study in hip fracture discordant monozygotic twins. All 286 identical Swedish twin pairs discordant for hip fracture (1972-2010) were identified. Comorbidity and lifestyle information was retrieved by registers and questionnaire information. We used intrapair Cox regression to compute multivariable-adjusted hazard ratios (HRs) for death. During follow-up, 143 twins with a hip fracture died (50%) compared to 101 twins (35%) without a hip fracture. Through the first year after hip fracture, the rate of death increased four-fold in women (HR 3.71; 95% confidence interval (CI) 1.32-10.40) and seven-fold in men (HR 6.67; 95% CI 1.47-30.13). The increased rate in women only persisted during the first year after hip fracture (HR after 1 year 0.99; 95% CI 0.66-1.50), whereas the corresponding HR in men was 2.58 (95% CI 1.02-6.62). The higher risk in men after the hip fracture event was successively attenuated during follow-up. After 5 years, the hazard ratio in men with a hip fracture was 1.19 (95% CI 0.29-4.90). On average, the hip fracture contributed to 0.9 years of life lost in women (95% CI 0.06-1.7) and 2.7 years in men (95% CI 1.7-3.7). The potential years of life lost associated with the hip fracture was especially pronounced in older men (>75 years), with an average loss of 47% (95% CI 31-61) of the expected remaining lifetime. We conclude that both women and men display a higher mortality after hip fracture independent of genes, comorbidity and lifestyle.

  • 42. Moller, Henrik
    et al.
    Purushotham, Arnie
    Linklater, Karen M.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lambe, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yallop, Deborah
    Devereux, Stephen
    Recent childbirth is an adverse prognostic factor in breast cancer and melanoma, but not in Hodgkin lymphoma2013In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 17, p. 3686-3693Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between gestation, childbirth and cancer prognosis is unknown for most cancers (e. g. Hodgkin lymphoma), whereas a body of evidence exists for melanoma and breast cancer. Methods: The national cancer registration and hospital discharge data for women in England (1998-2007) were linked, and the records for Hodgkin lymphoma, melanoma and breast cancer were indexed as to whether women had delivered a child in separate time periods prior to their cancer diagnosis. Survival analyses were conducted in order to characterise prognosis in relation to childbirth, with statistical adjustment for age and (where possible) stage. Findings: For melanoma and breast cancer, survival was strongly reduced in women who gave birth in the year prior to cancer diagnosis. The age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were 2.06 (1.42-3.01) for melanoma and 1.84 (1.64-2.06) for breast cancer. The associations were only slightly attenuated by further adjustment for tumour stage. For breast cancer, the excess death rate in women with a recent childbirth peaked at 2 years and remained elevated for 6 to 8 years. Previous childbirth had no overall effect on the outcome of Hodgkin lymphoma. Interpretation: Melanoma and breast cancer prognosis are adversely affected by recent gestation and childbirth in a way that is not due to stage of the cancer, but rather to inherent biological properties of the tumours. Possible biological mechanisms include immunosuppression (melanoma), the hormonal milieu in gestation and a tumour promoting microenvironment post-partum (breast cancer).

  • 43.
    Nderitu, Paul
    et al.
    Guys & St Thomas NHS Fdn Trust, Dept Oncol, London SE1 9RT, England..
    Bosco, Cecilia
    Kings Coll London, Div Canc Studies, TOUR, London, England..
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Div Canc Studies, TOUR, London, England.;Akad Sjukhuset, Reg Canc Ctr, Uppsala, Sweden..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Div Canc Studies, TOUR, London, England.
    Malmström, Hakan
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden..
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.;AstraZeneca, Med Evidence & Observat Res, Global Med Dev, Stockholm, Sweden..
    Walldius, Göran
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Jungner, Ingmar
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden.;CALAB Res, Stockholm, Sweden..
    Ross, Paul
    Guys & St Thomas NHS Fdn Trust, Dept Oncol, London SE1 9RT, England..
    Van Hemelrijck, Mieke
    Guys & St Thomas NHS Fdn Trust, Dept Oncol, London SE1 9RT, England.;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden..
    The association between individual metabolic syndrome components, primary liver cancer and cirrhosis: A study in the Swedish AMORIS cohort2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 6, p. 1148-1160Article in journal (Refereed)
    Abstract [en]

    Metabolic syndrome (MetS) is associated with non-alcoholic fatty liver disease, which may progress to cirrhosis, a significant risk factor of hepatocellular carcinoma (HCC), the commonest malignant primary liver cancer (PLC). We investigated the association between the individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity), PLC and cirrhosis. A total of 509,436 participants from the Swedish AMORIS cohort, recruited between January 1985 and December 1996 (end-date December 2011), aged >= 20 with baseline triglycerides (TG), total cholesterol (TC), glucose and liver enzymes were included. Those with baseline benign liver tumours, PLC or cirrhosis were excluded. Multivariate Cox regression, adjusted for age, gender, socio-economic status, liver disease (excluding cirrhosis) and MetS factors were used to estimate the association with PLC and cirrhosis. There were 766 PLC and 2,775 cirrhosis cases over 13 years. Raised TG, low TC, raised glucose, diabetes and low HDL were associated with an increased risk of developing PLC and cirrhosis. ApoB/ApoA-I ratio were also associated with PLC, whilst low LDL, raised TG/HDL, low ApoA-I and low ApoB were associated with cirrhosis. Obesity was significantly associated with PLC but not cirrhosis. Raised TG, low TC, raised glucose and diabetes showed stronger associations with PLC in participants with cirrhosis but many participants developed PLC without cirrhosis. Individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity) were associated with an increased risk of developing PLC or cirrhosis. MetS components were more strongly associated with PLC with preceding cirrhosis history but many participants developed PLC without cirrhosis.

  • 44.
    Nilsson, Greger
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sjögren, Iwar
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Distribution of Coronary Artery Stenosis After Radiation for Breast Cancer2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 4, p. 380-386Article in journal (Refereed)
    Abstract [en]

    PURPOSE

    To study distribution of coronary artery stenosis among patients with breast cancer (BC) and to assess correlation between radiotherapy (RT) and location of stenosis.

    PATIENTS AND METHODS

    A Swedish BC cohort diagnosed from 1970 to 2003 was linked to registers of coronary angiography from 1990 to 2004, which yielded 199 patients. Stenoses of the coronary arteries were graded from 0 to 5, where 0 indicated a normal vessel and 5 indicated occlusion. Two hotspot areas for radiation were defined: proximal right coronary artery (prox RCA), mid and distal left anterior descending artery and distal diagonal (mdLAD + dD). RT regimens were categorized as high or low risk of irradiating the hotspot areas. Left breast/chest wall was considered high risk for mdLAD + dD; left internal mammary chain (IMC), high risk for prox RCA and mdLAD + dD from 1970 to 1995 and thereafter solely for mdLAD + dD; and right IMC, high risk for prox RCA. Other RT targets and no RT were considered low risk. Results were expressed in odds ratios (ORs) and 95% CIs.

    RESULTS

    For irradiated left- versus right-sided BC, the OR for grade 3 to 5 stenosis in mdLAD + dD was 4.38 (95% CI, 1.64 to 11.7), and for grade 4 to 5 stenosis, the OR was 7.22 (95% CI, 1.64 to 31.8). For high-risk RT versus low-risk or no RT, the OR for grade 3 to 5 stenosis in hotspot areas was 1.90 (95% CI, 1.11 to 3.24).

    CONCLUSION

    An increase of stenosis in mdLAD + dD in irradiated left-sided BC and an association between high-risk RT and stenosis in hotspot areas for radiation indicate a direct link between radiation and location of coronary stenoses.

  • 45.
    Nilsson, Greger
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Terent, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Increased incidence of stroke in women with breast cancer2005In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 41, no 3, p. 423-429Article in journal (Refereed)
    Abstract [en]

    Meta-analyses have shown an excess of vascular deaths in women with breast cancer given radiotherapy (RT). In women with breast cancer, RT to the supraclavicular lymph nodes gives a substantial radiation dose to the proximal carotid artery. RT is known to increase the risk of carotid stenosis and ischaemic stroke in head and neck cancer. A study base of 25,171 women with breast cancer was defined. A linkage between the study base and the Hospital Discharge Register yielded 1766 women who were diagnosed with a stroke after a breast cancer. The observed number of strokes was compared with the expected number in the background population. The Relative Risk (RR) of stroke in the study group with breast cancer was 1.12 (95% Confidence Interval (CI)=1.07-1.17). The increased risk was confined to the subtype cerebral infarction, RR=1.12 (95% CI=1.05-1.19). A statistically significant increase in the risk of stroke was seen among women with a history of breast cancer. Whether this risk is associated with the breast cancer disease per se or related to any treatment requires further study.

  • 46. O'Farrell, Sean
    et al.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Adolfsson, Jan
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Van Hemelrijck, Mieke
    Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 11, p. 1243-1251Article in journal (Refereed)
    Abstract [en]

    Purpose Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent.

    Methods By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models.

    Results From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort.

    Conclusion Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

  • 47.
    Pettersson, A.
    et al.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Robinson, D.
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Garmo, Hans
    Univ Uppsala Hosp, Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden;Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Reply to the letter to the editor 'Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies' by X. Dong, G. Ma and F. Chen2018In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29, no 9, p. 2020-2021Article in journal (Other academic)
  • 48. Plym, Anna
    et al.
    Folkvaljon, Yasin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Fransson, Per
    Stattin, Par
    Lambe, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Drug Prescription for Erectile Dysfunction Before and After Diagnosis of Localized Prostate Cancer2014In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 11, no 8, p. 2100-2108Article in journal (Refereed)
    Abstract [en]

    Introduction. Despite the high prevalence of erectile dysfunction (ED) in men with prostate cancer, little is known about the use of ED drugs. Also, the possible influence of socioeconomic factors on ED drug use has not been studied previously. Aim. The aim of this study was to examine determinants and patterns of ED drug use before and after diagnosis in men with localized prostate cancer. Methods. Using a nationwide population-based cohort, 25,390 men with localized prostate cancer diagnosed between 2006 and 2009 and 126,944 control men were identified and followed for filled ED drug prescriptions over a 3-year period, ranging from 1 year before and up to 2 years after diagnosis. Main Outcome Measures. The main outcome measure was the proportion of men with at least one filled ED drug prescription after diagnosis. Results. The number of men using ED drugs increased markedly following diagnosis. Men who underwent radical prostatectomy had the strongest increase, with a cumulative proportion of 74% for at least one filled prescription within the first 2 years after diagnosis. The corresponding proportion was 33% in men treated with radiotherapy, 21% in men on active surveillance, 10% in men on watchful waiting, and 8% in control men. Among men who underwent prostatectomy, usage attenuated over time. Determinants of postdiagnostic use were young age at diagnosis, high income, high education, and a low- or intermediate-risk cancer. Conclusion. Although drugs for ED are commonly prescribed after diagnosis, use among most men is transient and influenced by socioeconomic status. Posttreatment counseling and affordable ED drugs are likely to reduce treatment dropout and disparities in use and help improve sexual health and quality of life in men with prostate cancer.

  • 49. Robinson, David
    et al.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Mucci, Lorelei
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stattin, Par
    Use of 5 alpha-reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study2013In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 346, p. f3406-Article in journal (Refereed)
    Abstract [en]

    Objective To assess the association between 5 alpha-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk. Design Nationwide, population based case-control study for men diagnosed with prostate cancer in 2007-09 within the Prostate Cancer data Base Sweden 2.0. Setting The National Prostate Cancer Register, National Patient Register, census, and Prescribed Drug Register in Sweden, from which we obtained data on 5-ARI use before date of prostate cancer diagnosis. Participants 26 735 cases and 133 671 matched controls; five controls per case were randomly selected from matched men in the background population. 7815 men (1499 cases and 6316 controls) had been exposed to 5-ARI. 412 men had been exposed to 5-ARI before the diagnosis of a cancer with Gleason score 8-10. Main outcome measures Risk of prostate cancer calculated as odds ratios and 95% confidence intervals by conditional logistic regression analyses. Results Risk of prostate cancer overall decreased with an increasing duration of exposure; men on 5-ARI treatment for more than three years had an odds ratio of 0.72 (95% confidence interval 0.59 to 0.89; P<0.001 for trend). The same pattern was seen for cancers with Gleason scores 2-6 and score 7 (both P<0.001 for trend). By contrast, the risk of tumours with Gleason scores 8-10 did not decrease with increasing exposure time to 5-ARI (for 0-1 year of exposure, odds ratio 0.96 (95% confidence interval 0.83 to 1.11); for 1-2 years, 1.07 (0.88 to 1.31); for 2-3 years, 0.96 (0.72 to 1.27); for >3 years, 1.23 (0.90 to 1.68); P=0.46 for trend). Conclusions Men treated with 5-ARI for lower urinary tract symptoms had a decreased risk of cancer with Gleason scores 2-7, and showed no evidence of an increased risk of cancer with Gleason scores 8-10 after up to four years' treatment.

  • 50. Robinson, David
    et al.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    5-alpha reductase inhibitors, benign prostatic hyperplasia, and risk of male breast cancer2015In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 26, no 9, p. 1289-1297Article in journal (Refereed)
    Abstract [en]

    5-alpha reductase inhibitors (5-ARI) have been suggested to increase the risk of male breast cancer. The aim of this study was to study the risk of breast cancer in men on 5-ARI, in men with benign prostatic hyperplasia (BPH) not on 5-ARI, and in men without BPH. We performed a population-based cohort study in Sweden with data from The Prescribed Drug Register, The Patient Register, and The Cancer Register. Men on 5-ARI, men on alpha-blockers, or men who had undergone a transurethral resection of the prostate (TUR-P) prior to or during 2006-2008 were included as exposed to BPH and a specific treatment thereof. For each exposed man, five unexposed men were selected. Risk of breast cancer was calculated in Cox proportional hazard models. There were 124,183 exposed men and 545,293 unexposed men, and during follow-up (median 6 years), 99 men with breast cancer were diagnosed. Compared to unexposed men, men on 5-ARI had a hazard ratio (HR) of breast cancer of 0.74 (95 % confidence interval (CI) 0.27-2.03), men on alpha-blockers had HR 1.47 (95 % CI 0.73-2.95), and men with a TUR-P had HR 1.99 (95 % CI 1.05-3.75). No increased risk of breast cancer was observed for men on 5-ARI. However, the increased risk of breast cancer among men who had undergone a TUR-P, a strong indicator of BPH, suggests that the endocrine milieu conducive to BPH is associated with male breast cancer.

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