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  • 1.
    Bratt, Ola
    et al.
    Department of Urology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Holmberg, Erik
    Regional Cancer Centre, Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Gothenburg, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Carlsson, Stefan
    Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Drevin, Linda
    Regional Cancer Centre, Uppsala-Örebro, Uppsala, Sweden.
    Johansson, Eva
    Department of Urology, Academic Hospital, Uppsala, Sweden.
    Josefsson, Andreas
    Department of Urology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nyberg, Maria
    Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sandberg, Jonas
    Department of Urology, Norrland University Hospital, Umeå, Sweden.
    Stattin, Pär
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Robinsson, David
    Department of Urology, Department of Urology, Jönköping County, Sweden.
    The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS)2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, no 4, p. 461-466Article in journal (Refereed)
    Abstract [en]

    Background: A systematic repeat biopsy is recommended for men starting on active surveillance for prostate cancer, but the optimal number and distribution of cores are unknown.

    Objective: To evaluate an extensive repeat transrectal biopsy with anterior sampling in men starting on active surveillance.

    Design, setting, and participants: Randomised multicentre trial. From 2012 to 2016, 340 Swedish men, aged 40-75 yr, with recently diagnosed low-volume Gleason grade group 1 prostate cancer were included.

    Intervention: Either an extensive transrectal biopsy with anterior sampling (median 19 cores) or a standard transrectal biopsy (median 12 cores).

    Outcome measurements and statistical analysis: Primary outcome measure: Gleason grade group >= 2 cancer. Secondary outcomes: Cancer in anteriorly directed biopsy cores and postbiopsy infection. Nonparametric statistical tests were applied.

    Results and limitations: Gleason grade group >= 2 cancer was detected in 16% of 156 men who had an extensive biopsy and in 10% of 164 men who had a standard biopsy, a 5.7% difference (95% confidence interval [CI]-0.2% to 13%, p = 0.09). There was a strong linear association between prostate-specific antigen (PSA) density and cancer in the anteriorly directed biopsy cores. The odds ratios for cancer in the anteriorly directed cores were for any cancer 2.2 (95% CI 1.3-3.9, p = 0.004) and for Gleason grade group >= 2 cancer 2.3 (95% CI 1.2-4.4, p = 0.015) per 0.1-ng/ml/cm(3) increments. Postbiopsy infections were equally common in the two groups. A limitation is that magnetic resonance imaging was not used.

    Conclusions: The trial did not support general use of the extensive transrectal repeat biopsy template, but cancer in the anteriorly directed cores was common, particularly in men with high PSA density. The higher the PSA density, the stronger the reason to include anterior sampling at a systematic repeat biopsy.

    Patient summary: This trial compared two different templates for transrectal prostate biopsy in men starting on active surveillance for low-risk prostate cancer. Cancer was often found in the front part of the prostate, which is not sampled on a standard prostate biopsy. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 2.
    Iglesias-Gato, Diego
    et al.
    IVS, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Centre for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Cancer Society, Copenhagen, Denmark.
    Wikström, Pernilla
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Tyanova, Stefka
    Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
    Lavallee, Charlotte
    IVS, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Centre for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Cancer Society, Copenhagen, Denmark.
    Thysell, Elin
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology.
    Hägglöf, Christina
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Cox, Jürgen
    Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Stattin, Pär
    Departments of Surgery and Perioperative Sciences, Umeå University, Umeå, Sweden.
    Egevad, Lars
    Section of Urology, Department of Surgical Science, Karolinska Institutet, Stockholm, Sweden.
    Widmark, Anders
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Bjartell, Anders
    Department of Translational Medicine, Division of Urological Cancers, University of Lund, Lund, Sweden.
    Collins, Colin C.
    Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
    Bergh, Anders
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Geiger, Tamar
    Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
    Mann, Matthias
    Novo Nordisk Foundation Centre for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
    Flores-Morales, Amilcar
    IVS, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Centre for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Cancer Society, Copenhagen, Denmark.
    The Proteome of Primary Prostate Cancer2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, no 5, p. 942-952Article in journal (Refereed)
    Abstract [en]

    Background: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries.

    Objectives: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers for disease aggressiveness.

    Design, setting, and participants: Mass spectrometry was used for genome-scale quantitative proteomic profiling of 28 prostate tumors (Gleason score 6-9) and neighboring nonmalignant tissue in eight cases, obtained from formalin-fixed paraffin-embedded prostatectomy samples. Two independent cohorts of PCa patients (summing 752 cases) managed by expectancy were used for immunohistochemical evaluation of proneuropeptide-Y (pro-NPY) as a prognostic biomarker.

    Results and limitations: Over 9000 proteins were identified as expressed in the human prostate. Tumor tissue exhibited elevated expression of proteins involved in multiple anabolic processes including fatty acid and protein synthesis, ribosomal biogenesis and protein secretion but no overt evidence of increased proliferation was observed. Tumors also showed increased levels of mitochondrial proteins, which was associated with elevated oxidative phosphorylation capacity measured in situ. Molecular analysis indicated that some of the proteins overexpressed in tumors, such as carnitine palmitoyltransferase 2 (CPT2, fatty acid transporter), coatomer protein complex, subunit alpha (COPA, vesicle secretion), and mitogen-and stress-activated protein kinase 1 and 2 (MSK1/2, protein kinase) regulate the proliferation of PCa cells. Additionally, pro-NPY was found overexpressed in PCa (5-fold, p < 0.05), but largely absent in other solid tumor types. Pro-NPY expression, alone or in combination with the ERG status of the tumor, was associated with an increased risk of PCa specific mortality, especially in patients with Gleason score <= 7 tumors.

    Conclusions: This study represents the first system-wide quantitative analysis of proteome changes associated to localized prostate cancer and as such constitutes a valuable resource for understanding the complex metabolic changes occurring in this disease. We also demonstrated that pro-NPY, a protein that showed differential expression between high and low risk tumors in our proteomic analysis, is also a PCa specific prognostic biomarker associated with increased risk for disease specific death in patients carrying low risk tumors.

    Patient summary: The identification of proteins whose expression change in prostate cancer provides novel mechanistic information related to the disease etiology. We hope that future studies will prove the value of this proteome dataset for development of novel therapies and biomarkers. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 3.
    Jahnson, S.
    et al.
    Örebro Medical Centre, Örebro, Sweden.
    Risberg, B.
    Karlsson, Mats G.
    Örebro Medical Centre, Örebro, Sweden.
    Westman, G.
    Bergström, R.
    Pedersen, J.
    p53 and Rb immunostaining in locally advanced bladder cancer: relation to prognostic variables and predictive value for the local response to radical radiotherapy1995In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 28, no 2, p. 135-142Article in journal (Refereed)
    Abstract [en]

    The association between known prognostic variables and altered immunostaining for the nuclear proteins retinoblastoma (Rb) and p53 was studied in a homogeneous series of locally advanced bladder cancer. The predictive value of this immunostaining for the local response to intended radical radiotherapy was investigated. Among 262 patients treated with intended radical radiotherapy between 1967 and 1986, a total of 154 patients were evaluable with respect to local response to treatment. The paraffin-embedded specimen from the tumour prior to irradiation was immunostained with the monoclonal antibodies PMG3-245 for Rb and 1801 for p53 nuclear proteins after heating in a microwave oven for 40 min at 650 W. An altered expression of Rb and p53 was observed in 18 and 42% of the tumours, respectively. p53 overexpression was associated with higher tumour grade. However, the results of the p53 and Rb immunostaining procedures had no predictive value for tumor response to radiation treatment, local control or cancer-specific mortality.

  • 4. Johansson, Eva
    et al.
    Bill-Axelson, Anna
    Holmberg, Lars
    Onelöv, Erik
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Steineck, Gunnar
    Time, Symptom Burden, Androgen Deprivation, and Self-Assessed Quality of Life after Radical Prostatectomy or Watchful Waiting: The Randomized Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) Clinical Trial2008In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 55, no 2, p. 422-432Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Quality-of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer.

    OBJECTIVE: To evaluate how follow-up time, number of physical symptoms, and presence of androgen deprivation affected quality of life among men randomized to radical prostatectomy or watchful waiting.

    DESIGN, SETTING, AND PARTICIPANTS: The study group was composed of all 376 living men included in the Swedish part of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) between January 1, 1989, and February 29, 1996. Quality-of-life data were collected after a mean follow-up time of 4.1 yr.

    INTERVENTION: All patients were randomly assigned to radical prostatectomy or watchful waiting. Forty-five men were androgen deprived.

    MEASUREMENTS: Data of specific symptoms, symptom-induced stress, sense of well-being, and self-assessed quality of life were obtained by means of a questionnaire. Psychological symptoms were assessed using seven-point visual digital scales.

    RESULTS AND LIMITATIONS: In analyses stratified on the basis of the numbers of physical symptoms, anxiety and depressed mood were less common, and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group. As the number of physical symptoms increased, all psychological variables became worse and more prominent in the watchful waiting group. After a follow-up time of 6-8 yr, a significant decrease in quality of life (p=0.03) was seen in the watchful waiting group. Twenty-four percent of androgen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60% in the radical prostatectomy group. Eighty-eight percent of patients had clinically detected tumors.

    CONCLUSIONS: Androgen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting. The number of physical symptoms was associated with the level of quality of life. Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group (p=0.03).

  • 5.
    Leijte, Joost A. P.
    et al.
    The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
    Kirrander, Peter
    Örebro University Hospital.
    Antonini, Ninja
    The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
    Windahl, Torgny
    Örebro University Hospital.
    Horenblas, Simon
    The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
    Recurrence patterns of squamous cell carcinoma of the penis: Recommendations for follow-up based on a two-centre analysis of 700 patients2008In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 54, no 1, p. 161-169Article in journal (Refereed)
    Abstract [en]

    Background: Current follow-up recommendations for patients with penile carcinoma are based on small numbers of patients.

    Objectives: To give further insight into the recurrence patterns of penile carcinoma in different treatment settings and provide recommendations for follow up.

    Designs, Setting, and Participants: In this retrospective study, we analysed 700 patients from two referral centres for penile carcinoma for recurrences.

    Measurements: Recurrences were categorized as local, regional, or distant. The rate of local recurrences was compared between patients undergoing penile-preserving treatments and partial/total amputation. Regional recurrences were compared between patients surgically staged as pN0 or pN+ and clinically node-negative (cN0) patients subjected to a wait-and-see policy. The total recurrence rate, type of recurrence, time to recurrence, and survival were calculated.

    Results and Limitations: 205 out of 700 patients (29.3%) had a recurrence, consisting of 18.6% local, 9.3% regional, and 1.4% distant recurrences. Of the recurrences, 92.2% occurred within 5 yr after primary treatment. All regional and distant recurrences occurred within 50 and 16 mo, respectively. The local recurrence rate was 27.7% after penile-preserving therapy and 5.3% after amputation. The regional recurrence rate was 2.3% in patients staged as pN0, 19.1% in patients staged as pN+, and 9.1% in patients undergoing a wait-and-see policy. The 5-yr disease-specific survival was 92% after a local recurrence and 32.7% after a regional recurrence. All patients with a distant recurrence died within 22 mo. Although the number of analysed patients is substantial, the results do not necessarily reflect those of other centres using different techniques for the management of penile carcinoma.

    Conclusions: Patients undergoing penile-preserving therapy, patients surgically staged as pN+, and those undergoing a wait-and-see policy for the nodal status are at high risk of developing a recurrence. Follow-up recommendations are provided based on the risk and impact on survival of a recurrence.

  • 6.
    Meyer, Mara S.
    et al.
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States.
    Mucci, Lorelei A.
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States; Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston MA, United States.
    Andersson, Swen-Olof
    Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Örebro University Hospital, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University Hospital, Örebro, Sweden.
    Tretli, Steinar
    Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
    Adami, Hans-Olov
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Homogeneous prostate cancer mortality in the Nordic countries over four decades2010In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 58, no 3, p. 427-32Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Incidence of prostate cancer (PCa) has greatly increased in the Nordic region over the past two decades, following the advent of prostate-specific antigen (PSA) screening. Consequently, interpreting temporal trends in PCa has become difficult, and the impact of changes in exposure to causal factors is uncertain.

    OBJECTIVE: To reveal geographic differences and temporal trends in PCa in the Nordic countries. Because the recorded incidence of PCa has been profoundly influenced by PSA screening, we focused our analyses primarily on PCa mortality.

    DESIGN, SETTING, AND PARTICIPANTS: We analyzed national PCa incidence and mortality data from Denmark, Finland, Norway, and Sweden from 1965 to 2006 using the PC-NORDCAN software program and the online NORDCAN database.

    MEASUREMENTS: Cumulative incidence and cumulative mortality from PCa were calculated for selected calendar years during four decades, along with age-standardized mortality rates. Incidence data in NORDCAN come from individual countries' cancer registries, and mortality data come from national mortality registries.

    RESULTS AND LIMITATIONS: From 1965 to 2006, 172 613 deaths from PCa were reported in the four Nordic countries. A substantial rise in incidence was observed across the region, with some geographic variation, since the late 1980s. In contrast, both disease-specific mortality rates and cumulative risk of PCa mortality lacked consistent temporal trends over the same period. Cumulative mortality from PCa ranged between 3.5% and 7.5% in the region over four decades, whereas cumulative incidence jumped from about 9% to >20%. Mortality has remained fairly constant among the countries, with a minimally lower risk in Finland.

    CONCLUSIONS: Unlike most malignancies, the occurrence of lethal PCa showed minimal geographic variation and lacked consistent temporal trends over four decades. These findings may guide our search for important causes of PCa, a malignancy with etiology that is still largely unknown.

  • 7.
    Patel, Hitendra R H
    et al.
    Dept Urol, Univ Hosp Northern Norway, Tromsø, Norway.
    Cerantola, Yannick
    Dept Urol, Univ Lausanne Hosp, Lausanne, Switzerland.
    Valerio, Massimo
    Dept Urol, Univ Lausanne Hosp, Lausanne, Switzerland.
    Persson, Beata
    Department of Urology, University Hospital of Örebro, Örebro, Sweden.
    Jichlinski, Patrice
    Dept Urol, Univ Lausanne Hosp, Lausanne, Switzerland.
    Ljungqvist, Olle
    Örebro University Hospital. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Hubner, Martin
    Dept Visceral Surg, Univ Lausanne Hosp, Lausanne, Switzerland.
    Kassouf, Wassim
    Dept Urol, McGill Univ, Montreal PQ, Canada.
    Müller, Stig
    Dept Urol, Akershus Univ Hosp, Oslo, Norway.
    Baldini, Gabriele
    Dept Anesthesia, McGill Univ, Montreal PQ, Canada.
    Carli, Francesco
    Dept Anesthesia, McGill Univ, Montreal PQ, Canada.
    Naesheim, Torvind
    Dept Anesthesia & Intens Care, Univ Hosp Northern Norway, Tromsø, Norway.
    Ytrebo, Lars
    Dept Anesthesia & Intens Care, Univ Hosp Northern Norway, Tromsø, Norway.
    Revhaug, Arthur
    Dept GI Surg, Univ Hosp Northern Norway, Tromsø, Norway.
    Lassen, Kristoffer
    Dept GI Surg, Univ Hosp Northern Norway, Tromsø, Norway.
    Knutsen, Tore
    Dept Urol, Univ Hosp Northern Norway, Tromsø, Norway.
    Aarsaether, Erling
    Dept Urol, Univ Hosp Northern Norway, Tromsø, Norway.
    Wiklund, Peter
    Dept Urol, Karolinska Univ Hosp, Stockholm, Sweden.
    Catto, James W F
    Acad Urol Unit, Univ Sheffield, Sheffield, England.
    Enhanced recovery after surgery: are we ready, and can we afford not to implement these pathways for patients undergoing radical cystectomy?2014In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 65, no 2, p. 263-266Article in journal (Refereed)
    Abstract [en]

    Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes.

  • 8.
    Popiolek, Marcin
    et al.
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Rider, Jennifer R.
    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston MA, USA .
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Andersson, Sven-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Holmberg, Lars
    Regional Oncologic Center, University Hospital, Uppsala, Sweden; Medical School, Division of Cancer Studies, King's College London, London, UK.
    Adami, Hans-Olov
    Department of Epidemiology, Harvard School of Public Health, Boston MA, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Natural history of early, localized prostate cancer: A final report from three decades of follow-up2013In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, no 3, p. 428-435Article in journal (Refereed)
    Abstract [en]

    Background: Most localized prostate cancers are believed to have an indolent course. Within 15 yr of diagnosis, most deaths among men with prostate cancer (PCa) can be attributed to other competing causes. However, data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease.

    Objective: To investigate the long-term natural history of untreated, early-stage PCa.

    Design, setting, and participants: We conducted a population-based, prospective-cohort study using a consecutive sample of 223 patients with untreated, localized PCa from a regionally well-defined catchment area in central Sweden. All subjects were initially managed with observation. Androgen deprivation therapy was administered when symptomatic tumor progression occurred.

    Outcome measurements and statistical analysis: Based on >30 yr of follow-up, the main outcome measures were: progression-free, cause-specific, and overall survival, and rates of progression and mortality per 1000 person-years.

    Results and limitations: After 32 yr of follow-up, all but 3 (1%) of the 223 men had died. We observed 90 (41.4%) local progression events and 41 (18.4%) cases of progression to distant metastasis. In total, 38 (17%) men died of PCa. Cause-specific survival decreased between 15 and 20 yr, but stabilized with further follow-up. All nine men with Gleason grade 8-10 disease died within the first 10 yr of follow-up, five (55%) from PCa. Survival for men with well-differentiated, nonpalpable tumors declined slowly through 20 yr, and more rapidly between 20 and 25 yr (from 75.2% [95% confidence interval, 48.4-89.3] to 25% [95% confidence interval, 22.0-72.5]). It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels.

    Conclusions: Although localized PCa most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis.

  • 9.
    Rider, Jennifer R.
    et al.
    Sch Publ Hlth, Dept Epidemiol, Harvard Univ, Boston MA, USA; Sch Med, Harvard Univ, Boston MA, USA; Dept Med, Channing Lab, Brigham & Womens Hosp, Boston MA, USA.
    Sandin, Fredrik
    Reg Canc Ctr, Uppsala, Sweden.
    Andrén, Ove
    Örebro University Hospital. Dept Urol.
    Wiklund, Peter
    Dept Mol Med & Surg, Div Urol, Karolinska Inst, Stockholm, Sweden.
    Hugosson, Jonas
    Dept Urol, Inst Clin Sci, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    Stattin, Par
    Dept Surg & Perioperat Sci Urol & Androl, Umeå Univ, Umeå, Sweden; Dept Surg, Urol Serv, Memorial Sloan Kettering Cancer Center, New York NY, USA.
    Long-term Outcomes Among Noncuratively Treated Men According to Prostate Cancer Risk Category in a Nationwide, Population-based Study2013In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, no 1, p. 88-96Article in journal (Refereed)
    Abstract [en]

    Background: Limited data exist on long-term outcomes among men with prostate cancer (PCa) from population-based cohorts incorporating information on clinical risk category. Objective: To assess 15-yr mortality for men with PCa treated with noncurative intent according to clinical stage, Gleason score (GS), serum levels of prostate specific antigen (PSA), comorbidity, and age. Design, setting, and participants: Register-based cohort study of 76 437 cases in the National Prostate Cancer Register (NPCR) of Sweden diagnosed from 1991 through 2009 and treated with noncurative intent. Each case was placed in one of five risk categories: (1) low risk: T1-T2 tumor, PSA level <10 ng/ml, and GS <= 6; (2) intermediate risk: T1-T2 tumor and PSA level 10-<20 ng/ml or GS 7; (3) high risk: T3 tumor or PSA level 20-<50 ng/ml or GS >= 8; (4) regional metastases: N1 or T4 tumor or PSA level 50-100 ng/ml; and (5) distant metastases: M1 tumor or PSA >= 100 ng/ml. Outcome measurements and statistical analysis: Ten-and 15-yr cumulative risk of death after diagnosis from PCa, cardiovascular disease, and other causes. Results and limitations: Among men with a Charlson Comorbidity Index (CCI) score of 0, no differences were found in observed versus expected all-cause mortality in the low-risk group. Observed mortality was only slightly greater in the intermediate-risk group, but men with high-risk localized PCa or more advanced disease had substantially higher mortality than expected. CCI was strongly associated with cumulative 10-yr mortality from causes other than PCa, especially for men <65 yr. Limitations include potential misclassification in risk category due to GS assignment. Conclusions: PCa mortality rates vary 10-fold according to risk category. The risk of death from causes other than PCa is most strongly related to comorbidity status in younger men. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.

  • 10.
    Sigurdardottir, Lara G.
    et al.
    Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Icelandic Cancer Society, Reykjavik, Iceland .
    Markt, Sarah C.
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States .
    Rider, Jennifer R.
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, United States .
    Haneuse, Sebastien
    Department of Biostatistics, Harvard School of Public Health, Boston MA, United States.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston MA, United States; Clinical Epidemiology Unit, Örebro University, Örebro University Hospital, Örebro, Sweden .
    Schernhammer, Eva S.
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, United States .
    Tamimi, Rulla M.
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston,MA, United States .
    Flynn-Evans, Erin
    Division of Sleep Medicine, Harvard Medical School, Boston MA, United States; Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston MA, United States .
    Batista, Julie L.
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, United States .
    Launer, Lenore
    Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda MD, United States .
    Harris, Tamara
    Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda MD, United States .
    Aspelund, Thor
    Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Kopavogur, Iceland .
    Stampfer, Meir J.
    Department of Epidemiology, Harvard School of Public Health, Boston MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, United States .
    Gudnason, Vilmundur
    Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Kopavogur, Iceland .
    Czeisler, Charles A.
    Division of Sleep Medicine, Harvard Medical School, Boston MA, United States; Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston MA, United States .
    Lockley, Steven W.
    Division of Sleep Medicine, Harvard Medical School, Boston MA, United States; Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston MA, United States .
    Valdimarsdottir, Unnur A.
    Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston MA, United States .
    Mucci, Lorelei A.
    Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, United States.
    Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, no 2, p. 191-194Article in journal (Refereed)
    Abstract [en]

    Melatonin has anticarcinogenic properties in experimental models. We undertook a case-cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders. A total of 111 men were diagnosed with incident PCa, including 24 with advanced disease. Men who reported sleep problems at baseline had lower morning aMT6s levels compared with those who reported no sleep problems. Men with morning aMT6s levels below the median had a fourfold statistically significant increased risk for advanced disease compared with men with levels above the median (hazard ratio: 4.04; 95% confidence interval, 1.26-12.98). These results require replication in larger prospective studies with longer follow-up.

    Patient summary: In this report, we evaluated the prospective association between urinary aMT6s levels and risk of PCa in an Icelandic population. We found that lower levels of aMT6s were associated with an increased risk for advanced PCa.

  • 11.
    Skeppner, Elisabet
    et al.
    Örebro University, School of Health and Medical Sciences.
    Windahl, Torgny
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Sjögren Fugl-Meyer, Kerstin
    Treatment-seeking, aspects of sexual activity and life satisfaction in men with laser-treated penile carcinoma2008In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 54, no 3, p. 631-639Article in journal (Refereed)
    Abstract [en]

    ObjectivesThe aims were to assess the initial symptoms of penile carcinoma and patients’ time frame in treatment seeking, and to describe the effect of laser treatment on sexual activity and life satisfaction.Patients and methodsA retrospective face-to-face structured interview study of patients laser treated for localised penile carcinoma at the department of Urology in Örebro, Sweden, during 1986 to 2000. Sixty-seven was treated and 58 of them (mean age, 63 yr; range, 34–90) were alive at the time of this study. Forty-six (79%) agreed to participate.ResultsNinety-six percent of the patients recalled their first symptom of penile carcinoma. Superficial ulceration and fissures were the most common symptoms (39%). Thirty-seven percent delayed seeking treatment for more than 6 mo.The patients had a greater lifetime number of sexual partners and a greater lifetime prevalence of STIs than a Swedish representative comparator population.Some aspects of sexual life, such as manual stimulation/caressing and fellatio, decreased markedly after laser treatment.Patient satisfaction with life as a whole was approximately the same as that of the general population.ConclusionsPatients delayed seeking treatment for a considerable period, despite awareness of the first local symptoms. Men with laser-treated localised penile carcinoma resume their sexual activities to a large extent after the treatment. Except for satisfaction with somatic health, similar—or even higher—proportions of patients than comparators are satisfied with life as a whole and with other domains of life including satisfaction with sexual life.Take Home MessageIn this study of 46 men who received laser treatment for localised penile carcinoma, we found that they resumed their sexual activities to a great extent and coped well with nearly all aspects of life after the treatment.

  • 12. Tilling, Kate
    et al.
    Garmo, Hans
    Metcalfe, Chris
    Holmberg, Lars
    Hamdy, Freddie C.
    Neal, David E.
    Adolfsson, Jan
    Martin, Richard M.
    Davis, Michael
    Fall, Katja
    Lane, J. Athene
    Adami, Hans-Olaf
    Bill-Axelson, Anna
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Donovan, Jenny L.
    Development of a new method for monitoring prostate-specific antigen changes in men with localised prostate cancer: a comparison of observational cohorts2010In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, no 3, p. 446-452Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prostate-specific antigen (PSA) measurements are increasingly used to monitor men with localised prostate cancer (PCa), but there is little consensus about the method to use. OBJECTIVE: To apply age-specific predictions of PSA level (developed in men without cancer) to one cohort of men with clinically identified PCa and one cohort of men with PSA-detected PCa. We hypothesise that among men with clinically identified cancer, the annual increase in PSA level would be steeper than in men with PSA-detected cancer. DESIGN, SETTING, AND PARTICIPANTS: The Scandinavian Prostate Cancer Group 4 (SPCG-4) cohort consisted of 321 men assigned to the watchful waiting arm of the SPCG-4 trial. The UK cohort consisted of 320 men with PSA-detected PCa in the Prostate testing for cancer and Treatment (ProtecT) study who opted for monitoring. Multilevel models describing changes in PSA level were fitted to the two cohorts, and average PSA level at age 50, change in PSA level with age, and predicted PSA values were derived. MEASUREMENTS: PSA level. RESULTS AND LIMITATIONS: In the SPCG-4 cohort, mean PSA at age 50 was similar to the cancer-free cohort but with a steeper yearly increase in PSA level (16.4% vs 4.0%). In the UK cohort, mean PSA level was higher than that in the cancer-free cohort (due to a PSA biopsy threshold of 3.0 ng/ml) but with a similar yearly increase in PSA level (4.1%). Predictions were less accurate for the SPCG-4 cohort (median difference between observed and predicted PSA level: -2.0 ng/ml; interquartile range [IQR]: -7.6-0.7 ng/ml) than for the UK cohort (median difference between observed and predicted PSA level: -0.8 ng/ml; IQR: -2.1-0.1 ng/ml). CONCLUSIONS: In PSA-detected men, yearly change in PSA was similar to that in cancer-free men, whereas in men with symptomatic PCa, the yearly change in PSA level was considerably higher. Our method needs further evaluation but has promise for refining active monitoring protocols.

  • 13.
    Vickers, A.
    et al.
    Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York NY, United States.
    Bennette, C.
    Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle WA, United States.
    Steineck, G.
    Karolinska Institute, Stockholm, Sweden.
    Adami, H. O.
    Harvard School of Public Health, Boston MA, United States.
    Johansson, J. E.
    Urologen, Örebro University Hospital, Örebro, Sweden.
    Bill-Axelson, A.
    University Hospital Uppsala, Uppsala, Sweden.
    Palmgren, J.
    Karolinska Institute, Stockholm, Sweden.
    Garmo, H.
    King's College London School of Medicine, London, United Kingdom; Regional Oncologic Centre Uppsala/Örebro, Uppsala, Sweden.
    Holmberg, L.
    Regional Oncologic Centre Uppsala/Örebro, Uppsala, Sweden.
    Individualized estimation of the benefit of radical prostatectomy from the Scandinavian prostate cancer group randomized trial2012In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 62, no 2, p. 204-209Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although there is randomized evidence that radical prostatectomy improves survival, there are few data on how benefit varies by baseline risk.

    OBJECTIVE: We aimed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient, using stage, grade, prostate-specific antigen, and age as predictors.

    DESIGN, SETTING, AND PARTICIPANTS: A total of 695 men with T1 or T2 prostate cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4).

    INTERVENTION: Patients in SPCG-4 were randomized to radical prostatectomy or conservative management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Competing risk models were created separately for the radical prostatectomy and the watchful waiting group, with the difference between model predictions constituting the estimated benefit for an individual patient.

    RESULTS AND LIMITATIONS: Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics. At 65 yr of age, the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5% to 17.2% for low- versus high-risk patients. Little expected benefit was associated with surgery much beyond age 70. Only about a quarter of men had an individualized benefit within even 50% of the mean. A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients.

    CONCLUSIONS: Our model suggests that it is hard to justify surgery in patients with Gleason 6, T1 disease or in those patients much above 70 yr of age. Conversely, surgery seems unequivocally of benefit for patients who have Gleason 8, or Gleason 7, stage T2. For patients with Gleason 6 T2 and Gleason 7 T1, treatment is more of a judgment call, depending on patient preference and other clinical findings, such as the number of positive biopsy cores and comorbidities.

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