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  • 51.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. 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 Study2016Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, nr 10, artikel-id djw110Artikel i tidskrift (Refereegranskat)
    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.

  • 52. Bratt, Ola
    et al.
    Folkvaljon, Yasin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eriksson, Marie Hjalm
    Akre, Olof
    Carlsson, Stefan
    Drevin, Linda
    Lissbrant, Ingela Franck
    Makarov, Danil
    Loeb, Stacy
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Undertreatment of Men in Their Seventies with High-risk Nonmetastatic Prostate Cancer2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, nr 1, s. 53-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. Objective: To investigate how age and comorbidity affect treatment of men with HRnMPCa. Design, setting, and participants: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. Outcome measurements and statistical analysis: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. Results and limitations: The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0-1. Only 10% of men aged 75-80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009-2012 for patients aged 70-80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed. Conclusions: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy. Patient summary: We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy.

  • 53.
    Bratt, Ola
    et al.
    Univ Oxford, Nuffield Dept Surg Sci, Oxford OX3 7DQ, England.;Lund Univ, Helsingborg Hosp, Dept Urol, Lund, Sweden.;Lund Univ, Helsingborg Hosp, Dept Urol, Helsingborg, Sweden..
    Folkvaljon, Yasin
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Loeb, Stacy
    NYU, Dept Urol, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Klotz, Laurence
    Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada..
    Egevad, Lars
    Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Upper limit of cancer extent on biopsy defining very low-risk prostate cancer2015Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 116, nr 2, s. 213-219Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. Patients and Methods We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern <= 3 only, prostate-specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic regression. Results In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and < 8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01). Conclusions Men aged < 70 years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1-2 cores with cancer, provided that the total biopsy cancer length is < 8 mm. We propose that the definition of very low-risk prostate cancer is widened accordingly.

  • 54. Bratt, Ola
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lambe, Mats
    Stattin, Pär
    Effects of Prostate-Specific Antigen Testing on Familial Prostate Cancer Risk Estimates2010Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 102, nr 17, s. 1336-1343Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Family history is a strong risk factor for prostate cancer. The aim of this study was to investigate whether increased diagnostic activity is related to the incidence of prostate cancer among brothers of men with prostate cancer. Methods Data were from the nationwide population-based Prostate Cancer Database Sweden (PCBaSe Sweden), which includes data from the National Prostate Cancer Register, the Swedish Cancer Register, the Register of the Total Population, the Multi-Generation Register, and the Census database. We investigated the relationship of tumor characteristics, time from diagnosis of the index patient (ie, prostate cancer patients in the National Prostate Cancer Register for whom at least one brother and their father could be identified), calendar period, geographic factors, and socioeconomic status to standardized incidence ratios (SIRs) for prostate cancer among 22 511 brothers of 13 975 index patients in PCBaSe Sweden. Results Brothers of index patients with prostate cancer were at increased risk for a diagnosis of prostate cancer (SIR = 3.1, 95% confidence interval [CI] = 2.9 to 3.3). Risk was higher for T1c tumors (SIR = 3.4, 95% CI = 3.2 to 3.8) than for metastatic tumors (SIR = 2.0, 95% CI = 1.5 to 2.6), and risk of T1c tumors was especially high during the first year after the diagnosis of the index patient (SIR = 4.3, 95% CI = 3.8 to 4.9), compared with the following years (SIR range = 2.8-3.3), and for brothers of index patients who had a higher socioeconomic status (SIR = 4.2, 95% CI = 3.7 to 4.7), compared with brothers of index patients with lower socioeconomic status (SIR = 2.8, 95% CI = 2.4 to 3.2). Conclusions Increased diagnostic activity among men with a family history of prostate cancer appears to contribute to their increased risk of prostate cancer and to lead to detection bias in epidemiological and genetic studies of familial prostate cancer.

  • 55.
    Bratt, Ola
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Urol, SE-41345 Gothenburg, Sweden.
    Holmberg, Erik
    Sahlgrens Univ Hosp, Reg Canc Ctr, Vastra Gotaland, Gothenburg, Sweden.
    Andren, Ove
    Orebro Univ Hosp, Dept Urol, Orebro, Sweden.
    Carlsson, Stefan
    Karolinska Inst, Dept Mol Med & Surg, Sect Urol, Stockholm, Sweden.
    Drevin, Linda
    Reg Canc Ctr, Uppsala, Sweden.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Josefsson, Andreas
    Univ Gothenburg, Sahlgrenska Acad, Dept Urol, SE-41345 Gothenburg, Sweden.
    Nyberg, Maria
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Sandberg, Jonas
    Norrland Univ Hosp, Dept Urol, Umea, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Robinsson, David
    Dept Urol, Jönköping, Jönköping Count, 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)2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 4, s. 461-466Artikel i tidskrift (Refereegranskat)
    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.

  • 56. Carducci, M.
    et al.
    Armstrong, A.
    Haggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stadler, W. M.
    Gingrich, J. R.
    Assikis, V.
    Forsberg, G.
    Olsson, A.
    Nordle, O.
    Pili, R.
    Tasquinimod mechanism of action biomarkers: correlation with pfs and survival in men with metastatic castrate resistant prostate cancer treated in a randomized phase 2 trial2012Ingår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, nr S9, s. 303-303Artikel i tidskrift (Övrigt vetenskapligt)
  • 57.
    Carlsson, Jörgen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Gedda, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Liljegren, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sjöström, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Westlin, Jan-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Zhao, Qinghai
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Lundqvist, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Conjugate chemistry and cellular processing of EGF-dextran1999Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, nr 3, s. 313-321Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.

  • 58.
    Carlsson, Jörgen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Wester, Kenneth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    De La Torre, Manuel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Gardmark, Truls
    EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides2015Ingår i: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 49, nr 1, s. 50-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder canter and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

  • 59. Carlsson, S.
    et al.
    Nilsson, A. E.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nyberg, T.
    Akre, O.
    Steineck, G.
    Self-perceived penile shortening after radical prostatectomy2012Ingår i: International journal of impotence research, ISSN 0955-9930, E-ISSN 1476-5489, Vol. 24, nr 5, s. 179-184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The postoperative effect on penile length after radical prostatectomy has been the subject of studies with conflicting results. We analyzed self-perceived penile shortening, quality of life and self-esteem after radical prostatectomy. In this cross-sectional study of a cohort of 1411 men who underwent a radical prostatectomy at Karolinska University Hospital between 2002 and 2006, we used a study-specific questionnaire. Patients and controls were asked about their perceived penile shortening by comparing present penile length now and at age 30 years. All subjects were also asked about their present quality of life and self-esteem. Patients were compared with 442 age-matched population-based controls. Among 1288 who underwent radical prostatectomy and answered the questionnaire (response rate 91%), 663 patients reported self-perceived penile shortening (55%), as compared with 85 (26%) of 350 men in the control group, corresponding to a relative risk (RR) of 2.1 (95% confidence interval (CI) 1.8-2.6) of self-perceived penile shortening compared with the age-matched control group. Age, grade of erectile dysfunction and angina were correlated with self-perceived penile shortening in both the operated and the control group. After adjustments for all of these mentioned potential confounders, we obtained a RR of 1.7 (95% CI 1.4-2.1) of self-perceived penile shortening compared with the controls. We also found that self-assessed penile shortening was associated with a RR of 1.2 (95% CI 1.1-1.3) for a low-to-moderate self-assessed quality of life and a RR of 1.2 (95% CI 1.1-1.4) for a low-to-moderate self estimation of self-esteem. Extensive nerve-sparing technique seems to be associated with less self-perceived penile shortening compared with radical prostatectomy with lower degree of nerve-sparing approach. These data indicate that radical prostatectomy is associated with self-perceived penile shortening and suggests that erectile function is a key factor in penile shortening.

  • 60.
    Carlsson, Sigrid
    et al.
    Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA.;Univ Gothenburg, Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden..
    Drevin, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Loeb, Stacy
    NYU, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Widmark, Anders
    Umea Univ, Oncol, Dept Radiat Sci, Umea, Sweden..
    Lissbrant, Ingela Franck
    Univ Gothenburg, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden..
    Robinson, David
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden.;Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stattin, Par
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden..
    Fransson, Per
    Umea Univ, Dept Nursing, Umea, Sweden..
    Population-based study of long-term functional outcomes after prostate cancer treatment2016Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, nr 6B, s. E36-E45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median (interquartile range) follow-up of 12 (11-13) years. Patients and Methods In this nationwide, population-based study, we identified 6 003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate-specific antigen <20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 from the National Prostate Cancer Register, Sweden. The men were aged <= 70 years at diagnosis. A control group of 1 000 men without prostate cancer were also selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire. Results Responses were obtained from 3 937/6 003 cases (66%) and 459/1 000 (46%) controls. At 12 years after diagnosis and at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction/sexual inactivity, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62, 6 and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction compared with the men in the control group. Radical prostatectomy was associated with an increased risk of urinary incontinence (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.36-2.62) and radiotherapy increased the risk of bowel dysfunction (OR 2.46, 95% CI 1.73-3.49) compared with men in the control group. Multimodal treatment, in particular treatment including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance, radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 (95% CI 1.76-7.95) for erectile dysfunction and an OR of 3.22 (95% CI 1.93-5.37) for urinary incontinence. Conclusion The proportion of men who experienced a long-term impact on functional outcomes after prostate cancer treatment was substantial.

  • 61. Carlsson, Sigrid
    et al.
    Sandin, Fredrik
    Fall, Katja
    Lambe, Mats
    Adolfsson, Jan
    Stattin, Par
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Risk of suicide in men with low-risk prostate cancer2013Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 7, s. 1588-1599Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Risk of suicide is increased among men with prostate cancer. We investigated this association among men with low-risk cancer, usually detected by prostate specific antigen (PSA)-testing. Patients and Methods: Relative risk (RR) of suicide was calculated by use of Poisson regression analysis within the Prostate Cancer data Base Sweden (PCBaSe) 2.0, a nation-wide, population-based database, comparing 105,736 men diagnosed with prostate cancer between 1997-2009 to 528,658 matched prostate cancer-free men. Results: During the first 6 months after diagnosis, there were 38 suicides among men with prostate cancer; incidence rate 0.73 per 1000 person-years (PY) and 30 suicides in the comparison cohort; 0.11 per 1000 PY, corresponding to a RR of suicide of 6.5 (95% confidence interval (CI) 4.0-10). Risk was highest among men with distant metastases, incidence rate 1.25 per 1000 PY, RR 10 (95% CI 5.1-21) but risk was also increased for men with low-risk tumours, incidence rate difference 0.45 per 1000 PY and RR 5.2 (95% CI 2.3-12) and across categories of socioeconomic status and comorbidity. Eighteen months after diagnosis, risk of suicide had decreased to 0.27 per 1000 PY, RR 1.0 (95% CI 0.68-1.5) for low-risk prostate cancer but remained increased among men with metastases, 0.57 per 1000 PY, RR 1.8 (95% CI 1.1-2.9). Conclusion: Although the increase in absolute risk of suicide was modest, our findings reflect the severe psychological stress that prostate cancer patients may experience after diagnosis. The increased risk of suicide observed in men with prostate cancer, including low-risk, calls for increased awareness.

  • 62.
    Cazzaniga, Walter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study2019Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, nr 3, s. 421-428Artikel i tidskrift (Refereegranskat)
    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.

  • 63.
    Cazzaniga, Walter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Univ Vita Salute San Raffaele, Osped San Raffaele, Unit Urol URI, IRCCS,Div Expt Oncol, Milan, Italy.
    Godtman, Rebecka Arnsrud
    Univ Goteborg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol,Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Carlsson, Stefan
    Karolinska Univ Hosp, Div Urol, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg MMK, Stockholm, Sweden.
    Ahlgren, Göran
    Lund Univ, Dept Urol, Skane Univ Hosp, Skane, Sweden.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Hugosson, Jonas
    Univ Goteborg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol,Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Population-based, nationwide registration of prostatectomies in Sweden2019Ingår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 120, nr 4, s. 803-812Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Radical prostatectomy (RP) is a common surgical procedure with a risk of postoperative erectile dysfunction and urinary incontinence. There is a need for data on RP as a basis for quality assurance and benchmarking. Methods In 2015, prostatectomies in Sweden (PiS) form was implemented in the National Prostate Cancer Register (NPCR) of Sweden with data on pre-, peri- and post-operative variables. Results Out of all radical prostatectomies performed in 2016 in Sweden, 3096/3881 (80%) were registered in PiS. A total of 2605 (84%) were robot-assisted radical prostatectomy (RARP) and 491 (16%) were RRP (retropubic radical prostatectomy). RARP was performed by 91 surgeons of whom 47% operated more than 25 RP/year; and RRP was performed by 69 surgeons of whom 10% performed more than 25 RP/year. RARP had a longer operative time (median operating time: RARP 155 minutes [IQR 124-190]; RRP 129 minutes [IQR 105-171]; P < .001) but was associated with smaller bleeding (median intraoperative blood loss: RARP 100 mL [IQR 50-200], RRP 700 mL [IQR 500-1100]; P < .001). Conclusions We report on a nationwide, population-based register with transparent reporting of data on the performance of radical prostatectomy. These data are needed as a basis for quality assurance with comparisons of results from individual surgeons and hospitals.

  • 64.
    Cazzaniga, Walter
    et al.
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Ventimiglia, Eugenio
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Alfano, Massimo
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Lissbrant, Ingela Franck
    Univ Goteborg, Sahlgrenska Acad, Dept Oncol, Inst Clin Sci, Gothenburg, Sweden.
    Carlsson, Stefan
    Karolinska Univ Hosp, Div Urol, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg MMK, Stockholm, Sweden.
    Styrke, Johan
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Salonia, Andrea
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Mini Review on the Use of Clinical Cancer Registers for Prostate Cancer: The National Prostate Cancer Register (NPCR) of Sweden2019Ingår i: FRONTIERS IN MEDICINE, ISSN 2296-858X, Vol. 6, artikel-id 51Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Given the increasing prevalence of cancer, it is vital to systematically collect data in order to monitor disease trends and quality of cancer care. For this purpose, clinical cancer registries have been developed in some countries. These registers are intended to be used as a basis for quality assurance and quality improvement, but they also constitute a rich resource of real world data for research. The aim of thismini-review was to describe the structure and the organization of the National Prostate Cancer Register (NPCR) with some examples on how data in NPCR have affected prostate cancer care in Sweden.

  • 65.
    Correa, P
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Åkerström, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Increased 25-hydroxyvitamin D3 1a-hydroxylase and reduced 25-hydroxyvitamin D3 24-hydroxylase expression in parathyroid tumors—New prospects for treatment of hyperparathyroidism with vitamin D.2002Ingår i: J Clin Endocrinol Metab,, Vol. 87, s. 5826-Artikel i tidskrift (Refereegranskat)
  • 66. Correa, Pamela
    et al.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Åkerström, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Increased 25-hydroxyvitamin D3 1α-hydroxylase and reduced 25-hydroxyvitamin D3 24-hydroxylase expression in parathyroid tumors: new prospects for treatment of hyperparathyroidism with vitamin D2002Ingår i: Journal of Clinical Endocrinology & Metabolism, ISSN 0021-972X, Vol. 87, nr 12, s. 5826-5829Artikel i tidskrift (Refereegranskat)
  • 67.
    Crawley, Danielle
    et al.
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Chamberlain, Florence
    Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England.
    Garmo, Hans
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Carroll, Paul
    Guys & St Thomas NHS Fdn Trust, Dept Diabet & Endocrinol, London, England.
    Van Hemelrijck, Mieke
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus2018Ingår i: ecancermedicalscience, ISSN 1754-6605, E-ISSN 1754-6605, Vol. 12, artikel-id 802Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions. It covers the impact of pre-existing T2DM on PCa incidence, grade and stage, as well as exploring the impact of T2DM on PCa outcomes and mortality and the interaction between T2DM and PCa treatments.

  • 68.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    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 cancer2016Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 139, nr 12, s. 2698-2704Artikel i tidskrift (Refereegranskat)
    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.

  • 69.
    Crawley, Danielle
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust & Kings Coll Londo, Comprehens Biomed Res Ctr, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Uppsala, Sweden.
    Armes, Jo
    Kings Coll London, Florence Nightingale Fac Nursing & Midwifery, London, England.
    Holmberg, Lars
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.
    Adolfsson, Jan
    Kings Coll London, Florence Nightingale Fac Nursing & Midwifery, London, England;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.
    Does a prostate cancer diagnosis affect management of pre-existing diabetes? Results from PCBaSe Sweden: a nationwide cohort study2018Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, nr 3, artikel-id e020787Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives Both prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are increasingly prevalent conditions, which frequently coexist in men. Here, we set out to specifically examine the impact of a PCa diagnosis and its treatment on T2DM treatment. Setting This study uses observational data from Prostate Cancer database Sweden Traject. Participants The study was undertaken in a cohort of 16778 men with T2DM, of whom 962 were diagnosed with PCa during mean follow-up of 2.5 years. Primary and secondary outcome measures We investigated the association between PCa diagnosis and escalation in T2DM treatment in this cohort. A treatment escalation was defined as a new or change in anti-T2DM prescription, as recorded in the prescribed drug register (ie, change from diet to meforrnin or sulphonylurea or insulin). We also investigated how PCa diagnosis was associated with two treatment escalations. Multivariate Cox proportional hazards regression with age as a time scale was used while adjusting for educational level and initial T2DM treatment. Results We found no association between PCa diagnosis and risk of a single treatment escalation (HR 0.99, 95% Cl 0.87 to 1.13). However, PCa diagnosis was associated with an increased risk of receiving two consecutive T2DM treatment escalations (HR 1.75, 95% CI 1.38 to 2.22). This increase was strongest for men on gonadotropin-releasing hormone (GnRH) agonists (HR 3.08, 95% Cl 2.14 to 4.40). The corresponding HR for men with PCa not on hormonal treatment was 1.40 (95% CI 1.03 to 1.92) and for men with PCa on antiandrogens 0.91 (95% Cl 0.29 to 2.82). Conclusions Men with T2DM who are diagnosed with PCa, particularly those treated with GnRH agonists, were more likely to have two consecutive escalations in T2DM treatment. This suggests a need for closer monitoring of men with both PCa and T2DM, as coexistence of PCa and its subsequent treatments could potentially worsen T2DM control.

  • 70.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Peri Operat Sci Urol & Androl, Umea, Sweden.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer.2018Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, nr 2, s. 209-216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

    SUBJECTS AND METHODS: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate- (T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

    RESULTS: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

    CONCLUSIONS: Men with T2DM were less likely to receive curative treatment for localized intermediate- and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under- nor overtreated.

  • 71. Crowe, Francesca L
    et al.
    Appleby, Paul N
    Travis, Ruth C
    Barnett, Matt
    Brasky, Theodore M
    Bueno-de-Mesquita, H Bas
    Chajes, Veronique
    Chavarro, Jorge E
    Chirlaque, Maria-Dolores
    English, Dallas R
    Gibson, Robert A
    Giles, Graham G
    Goodman, Gary E
    Henning, Susanne M
    Kaaks, Rudolf
    King, Irena B
    Kolonel, Lawrence N
    Kristal, Alan R
    Neuhouser, Marian L
    Park, Song-Yi
    Severi, Gianluca
    Siddiq, Afshan
    Stampfer, Meir J
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Tangen, Catherine M
    Tjønneland, Anne
    Trichopoulos, Dimitrios
    Tumino, Rosario
    Wilkens, Lynne R
    Key, Timothy J
    Allen, Naomi E
    Circulating fatty acids and prostate cancer risk: individual participant meta-analysis of prospective studies.2014Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 106, nr 109, artikel-id dju240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Individual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.

    METHODS: Principal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.

    RESULTS: Five thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18:0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, Ptrend = .001) and docosapentaenoic acid (22:5n-3) (OR = 1.16, 95% CI = 1.02 to 1.33, P trend = .003), but in each case there was heterogeneity between studies (P = .022 and P < .001, respectively). There was heterogeneity in the association between docosapentaenoic acid and prostate cancer by grade of disease (P = .006); the association was statistically significant for low-grade disease but not high-grade disease. The remaining 11 fatty acids were not statistically associated with total prostate cancer risk.

    CONCLUSION: There was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk. It is not clear whether the modest associations of stearic, eicosapentaenoic, and docosapentaenoic acid are causal.

  • 72.
    Dahlman, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Semenas, Egidijus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Brekkan, Einar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Bergman, Antonina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Detection and characterisation of renal lesions by multiphasic helical CT.2000Ingår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Acta Radiol., Vol. 41, nr 4, s. 361-366Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: The fast helical CT technique allows examination of the kidneys during different phases of contrast medium enhancement. However, every additional phase increases the radiation dosage to the patients. We investigated the detection rate and characterisation of renal lesions during different phases and evaluated them separately, and considered the possibility of excluding phases without loss of important information.

    MATERIAL AND METHODS: Sixty patients who underwent contrast-enhanced multiphasic renal helical CT examination were included. Every CT phase was evaluated separately. The number of lesions and the characteristics of the lesions were noted and all lesions were viewed together.

    RESULTS: A total of 153 cysts and 17 solid lesions were detected. The largest and an equal number of cysts (142/143) was detected in the nephrographic and excretory phases. However, the nephrographic phase detected more cortical cysts and the excretory phase detected more sinus cysts. All solid lesions were detected in all phases. Renal parenchymal tumours were best characterised in the cortical phase and angiomyolipomas in the native phase.

    CONCLUSION: The cortical phase was best for characterisation of renal parenchymal tumours. The nephrographic and excretory phases were best in detecting and characterising renal cysts. The nephrographic phase was the phase giving the least diagnostic information.

  • 73.
    Danielsson, Gun
    et al.
    Karolinska Univ Hosp, Patient Area Pelv Canc, Canc Theme, Stockholm, Sweden; Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Jahnson, Staffan
    Linköping Univ Hosp, Dept Urol, IKE, Linköping, Sweden.
    Wijkström, Hans
    Karolinska Univ Hosp, Patient Area Pelv Canc, Canc Theme, Stockholm, Sweden; Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Nyberg, Tommy
    Karolinska Inst, Dept Oncol Pathol, Clin Canc Epidemiol, Stockholm, Sweden; Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
    Thulin, Helena
    Karolinska Univ Hosp, Patient Area Pelv Canc, Canc Theme, Stockholm, Sweden; Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Bladder health in patients treated with BCG instillations for T1G2-G3 bladder cancer - a follow-up five years after the start of treatment2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 5-6, s. 377-384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) instillations.

    Materials and methods: Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients’ life.

    Results: In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being.

    Conclusion: Patients with bladder cancer T1G2–G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patient’s well-being. It is important to record the patients’ baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.

  • 74.
    Danneman, Daniela
    et al.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Drevin, Linda
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Delahunt, Brett
    Univ Otago, Wellington Sch Med & Hlth Sci, Wellington, New Zealand..
    Samaratunga, Hemamali
    Aquesta Pathol, Brisbane, Qld, Australia.;Univ Queensland, Sch Med, Brisbane, Qld, Australia..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Bratt, Ola
    Cambridge Univ Hosp, Dept Urol, Cambridge, England.;Lund Univ, Dept Translat Med, Lund, Sweden..
    Loeb, Stacy
    NYU, Dept Urol & Populat Hlth, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Egevad, Lars
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden..
    Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-20122017Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, nr 1, s. 50-56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

  • 75. Danneman, Daniela
    et al.
    Drevin, Linda
    Robinson, David
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Egevad, Lars
    Gleason inflation 1998-2011: a registry study of 97,168 men2015Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 115, nr 2, s. 248-55Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer.

    PATIENTS AND METHODS: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed.

    RESULTS: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned.

    CONCLUSIONS: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.

  • 76.
    Dansk, Viktor
    et al.
    PAREXEL, HERONtm Commercializat, Stockholm, Sweden..
    Malmstrom, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Blackberg, Mats
    Helsingborg Hosp, Dept Urol & Surg, Helsingborg, Sweden..
    Malmenas, Maria
    PAREXEL, HERONtm Commercializat, Stockholm, Sweden..
    Hexaminolevulinate hydrochloride blue-light flexible cystoscopy in the detection and follow-up of nonmuscle-invasive bladder cancer: cost consequences during outpatient surveillance in Sweden2016Ingår i: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 12, nr 8, s. 1025-1038Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: This study explored the cost consequences of introducing hexaminolevulinate hydrochloride-guided blue-light flexible cystoscopy (HAL BLFC) as an adjunct to white-light flexible cystoscopy compared with white-light flexible cystoscopy alone, for the detection and management of nonmuscle invasive bladder cancer in Sweden.

    Methods: The model evaluated 231 patients in the outpatient setting after successful initial transurethral resection of the bladder tumor.

    Results: HAL BLFC introduction across all risk groups resulted in minimal budget impact (+ 1.6% total cost/5 years, or 189 Swedish Krona [SEK] per patient/year), and translated to cost savings in intermediate-and high-risk groups from year 2.

    Conclusion: HAL BLFC allowed more outpatient treatment with improved recurrence detection and reduced transurethral resection of the bladder tumors, cystectomies, bed days and operating room time, with minimal cost impact across all risk groups, demonstrating the economic benefits of introducing HAL.

  • 77. de la Torre, M.
    et al.
    Eklöv, S.
    Häggman, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Björk, P.
    Busch, C.
    Nilsson, S.
    Elevated expression of estramustine binding protein (EMBP) in prostatic intraepithelial neoplasia (PIN) compared with malignant and benign prostatic epithelia1994Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 25, nr 3, s. 125-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The expression of estramustine-binding protein (EMBP) was studied immunohistochemically in whole-mount prostate sections. Specimens were taken from the prostates of 15 patients who had undergone total prostatectomy due to localized (TOd-T2 NO MO) prostatic cancer (PC). Almost all the examined whole-mount sections displayed areas with prostatic intraepithelial neoplasia (PIN). PIN is regarded as the main precursor of invasive PC. High- and low-grade PIN expressed EMBP. The average positively stained areas accounted for averages of 69.2% and 48.7%, respectively. High-grade PIN contained the highest EMBP levels of all the investigated (benign and malignant) epithelia, followed by moderately differentiated PC. With regard to areas with PC, the highest levels of EMBP expression (61.3%) were observed in moderately differentiated PC; poorly differentiated PC came second. Of all the examined epithelia, EMBP levels were lowest in well-differentiated PC (25.8%). Normal prostatic epithelia and hyperplasia were characterized by low EMBP expression, although somewhat higher than well-differentiated PC. A moderate expression (45%) was observed in the seminal vesicles. According to these results, EMBP was expressed mainly in the diseased peripheral zone (PZ), where PIN and prostatic cancer have their highest prevalence.

  • 78.
    Derogar, Maryam
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden..
    Dahlstrand, Hanna
    Karolinska Univ Hosptital, Dept Oncol, Stockholm, Sweden.;Karolinska Inst, Dept Oncol Pathol, Div Clin Canc Epidemiol, Stockholm, Sweden..
    Carlsson, Stefan
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Bjartell, Anders
    Lund Univ, Skane Univ Hosp, Dept Urol, Lund, Sweden..
    Hugosson, Jonas
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Axen, Elin
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Lagerkvist, Mikael
    UroClin, Stockholm, Sweden..
    Nyberg, Tommy
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Stranne, Johan
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Thorsteinsdottir, Thordis
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Univ Iceland, Sch Hlth Sci, Fac Nursing, Reykjavik, Iceland..
    Wallerstedt, Anna
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Haglind, Eva
    Univ Gothenburg, Sahlgrenska Acad, SSORG, Dept Surg,Inst Clin Sci, Gothenburg, Sweden..
    Wiklund, Peter
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Steineck, Gunnar
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Karolinska Inst, Dept Oncol Pathol, Div Clin Canc Epidemiol, Stockholm, Sweden..
    Preparedness for side effects and bother in symptomatic men after radical prostatectomy in a prospective, non-randomized trial, LAPPRO2016Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, nr 12, s. 1467-1476Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from urinary incontinence and decreased sexual health after surgery. Material and methods: We prospectively collected data from a non-selected group of men undergoing radical prostatectomy in 14 centers between 2008 and 2011. Before surgery, we asked about preparedness for surgery-induced urinary problems and decreased sexual health. One year after surgery, we asked about bother caused by urinary incontinence and erectile dysfunction. As a measure of the association between preparedness and bothersomeness we modeled odds ratios (ORs) by means of logistic regression. Results: Altogether 1372 men had urinary incontinence one year after surgery as well as had no urinary leakage or a small urinary dribble before surgery. Among these men, low preparedness was associated with bother resulting from urinary incontinence [OR 2.84; 95% confidence interval (CI) 1.59-5.10]. In a separate analysis of 1657 men we found a strong association between preparedness for decreased sexual health and experiencing bother from erectile dysfunction (OR 5.92; 95% CI 3.32-10.55). Conclusion: In this large-sized prospective trial, we found that preparedness before surgery for urinary problems or sexual side effects decreases bother from urinary incontinence and erectile dysfunction one year after surgery.

  • 79. Donovan, Michael J.
    et al.
    Khan, Faisal M.
    Fernandez, Gerardo
    Mesa-Tejada, Ricardo
    Sapir, Marina
    Zubek, Valentina Bayer
    Powell, Douglas
    Fogarasi, Stephen
    Vengrenyuk, Yevgen
    Teverovskiy, Mikhail
    Segal, Mark R.
    Karnes, R. Jeffrey
    Gaffey, Thomas A.
    Busch, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Hlavcak, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Freedland, Stephen J.
    Vollmer, Robin T.
    Albertsen, Peter
    Costa, Jose
    Cordon-Cardo, Carlos
    Personalized prediction of tumor response and cancer progression on prostate needle biopsy2009Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 182, nr 1, s. 125-132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To our knowledge in patients with prostate cancer there are no available tests except clinical variables to determine the likelihood of disease progression. We developed a patient specific, biology driven tool to predict outcome at diagnosis. We also investigated whether biopsy androgen receptor levels predict a durable response to therapy after secondary treatment. MATERIALS AND METHODS: We evaluated paraffin embedded prostate needle biopsy tissue from 1,027 patients with cT1c-T3 prostate cancer treated with surgery and followed a median of 8 years. Machine learning was done to integrate clinical data with biopsy quantitative biometric features. Multivariate models were constructed to predict disease progression with the C index to estimate performance. RESULTS: In a training set of 686 patients (total of 87 progression events) 3 clinical and 3 biopsy tissue characteristics were identified to predict clinical progression within 8 years after prostatectomy with 78% sensitivity, 69% specificity, a C index of 0.74 and a HR of 5.12. Validation in an independent cohort of 341 patients (total of 44 progression events) yielded 76% sensitivity, 64% specificity, a C index of 0.73 and a HR of 3.47. Increased androgen receptor in tumor cells in the biopsy highly significantly predicted resistance to therapy, ie androgen ablation with or without salvage radiotherapy, and clinical failure (p <0.0001). CONCLUSIONS: Morphometry reliably classifies Gleason pattern 3 tumors. When combined with biomarker data, it adds to the hematoxylin and eosin analysis, and prostate specific antigen values currently used to assess outcome at diagnosis. Biopsy androgen receptor levels predict the likelihood of a response to therapy after recurrence and may guide future treatment decisions.

  • 80. Duchek, Milos
    et al.
    Johansson, Robert
    Jahnson, Staffan
    Mestad, Oddvar
    Hellström, Pekka
    Hellsten, Sverker
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bacillus Calmette-Guerin Is Superior to a Combination of Epirubicin and Interferon-alpha 2b in the Intravesical Treatment of Patients with Stage T1 Urinary Bladder Cancer. A Prospective, Randomized, Nordic Study2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 1, s. 25-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bacillus Calmette-Guerin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed. Objective: To compare BCG to the combination of epirubicin and interferon-alpha 2b as adjuvant therapy of T1 tumours. Design, setting, and participants: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr. Measurements: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented. Results and limitations: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p = 0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p = 0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination. Conclusions: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

  • 81. Dyrskjot, L.
    et al.
    Reinert, T.
    Novoradovsky, A.
    Zuiverloon, T. C. M.
    Beukers, W.
    Zwarthoff, E.
    Malats, N.
    Real, F. X.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Knowles, M.
    Hurst, C.
    Sorge, J.
    Borre, M.
    Orntoft, T. F.
    Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR2012Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, nr 8, s. 1392-1398Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio = 7.4 (95% confidence interval: 3.4-15.9), P < 0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.

  • 82.
    Dyrskjot, Lars
    et al.
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Reinert, Thomas
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Algaba, Ferran
    Univ Autonoma Barcelona, Sect Pathol, Fundacio Puigvert, Barcelona, Spain.
    Christensen, Emil
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Nieboer, Daan
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
    Hermann, Gregers G.
    Frederiksberg Univ Hosp, Dept Urol, Frederiksberg, Denmark.
    Mogensen, Karin
    Frederiksberg Univ Hosp, Dept Urol, Frederiksberg, Denmark.
    Beukers, Willemien
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
    Marquez, Mirari
    Spanish Natl Canc Res Ctr, Madrid, Spain.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Hoyer, Soren
    Aarhus Univ Hosp, Dept Pathol, Aarhus, Denmark.
    Ulhoi, Benedicte P.
    Aarhus Univ Hosp, Dept Pathol, Aarhus, Denmark.
    Hartmann, Arndt
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany.
    Stohr, Robert
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany.
    Wach, Sven
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, Erlangen, Germany.
    Nawroth, Roman
    Tech Univ Munich, Dept Urol, Klinikum Rechts Isar, Munich, Germany.
    Schwamborn, Kristina
    Tech Univ Munich, Inst Pathol, Klinikum Rechts Isar, Munich, Germany.
    Tulic, Cane
    Univ Belgrade, Clin Ctr Serbia, Clin Urol, Fac Med, Belgrade, Serbia.
    Simic, Tatjana
    Univ Belgrade, Inst Med & Clin Biochem, Fac Med, Belgrade, Serbia.
    Junker, Kerstin
    Saarland Univ, Dept Urol, Homburg, Germany.
    Harving, Niels
    Aalborg Univ Hosp, Dept Urol, Aalborg, Denmark.
    Petersen, Astrid C.
    Aalborg Univ Hosp, Dept Pathol, Aalborg, Denmark.
    Jensen, Jorgen B.
    Aarhus Univ Hosp, Dept Urol, Aarhus, Denmark.
    Keck, Bastian
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, Erlangen, Germany.
    Grimm, Marc-Oliver
    Friedrich Schiller Univ Jena, Dept Urol, Jena, Germany.
    Horstmann, Marcus
    Friedrich Schiller Univ Jena, Dept Urol, Jena, Germany.
    Maurer, Tobias
    Tech Univ Munich, Dept Urol, Klinikum Rechts Isar, Munich, Germany.
    Steyerberg, Ewout W.
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
    Real, Francisco X.
    Spanish Natl Canc Res Ctr, Madrid, Spain;Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
    Malats, Nuria
    Spanish Natl Canc Res Ctr, Madrid, Spain.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 3, s. 461-469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/ 750 patients). Conclusions: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summary: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.

  • 83.
    Díaz de Ståhl, Teresita
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Molecular genetics of bladder cancer: an update2008Ingår i: Minerva Urologica e Nefrologica, ISSN 0393-2249, E-ISSN 1827-1758, Vol. 60, nr 4, s. 205-16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Urinary bladder cancer is a heterogeneous disease with tumors ranging from papillary non-invasive to solid muscle infiltrating high grade tumors. There are mainly three problems after initial management: recurrence, progression to higher stage and metastases. The respective risk is well known for each of the stages of the disease but not sufficiently for individual optimal risk assessments. The clinical need is initially to establish the correct risk irrespective of later treatment that is to find prognostic factors. Secondarily it is important to develop predictive factors for each specific therapy. With the advent of array-based molecular profiling it is possible to obtain a more complete picture of the cancer biology and thus hope to improve the prediction of risk. Today the microarray approach is implemented at DNA, RNA and protein level. Reported chromosomal alterations in low-grade papillary tumors are few and the most common are 9q and 9p deletions. Activation of the MAPK pathway through mutations of FGFR3, RAS or PI3K seems to be crucial in the genesis of these low malignant tumors. Muscle infiltrating bladder tumors typically have more genetic aberrations than non-muscle invasive cancers. Key genes are related to the p53 and RB pathways. Gene-expression signatures correlated to stage, CIS, progression and recurrence have been proposed but require further validation.

  • 84.
    Egevad, Lars
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Danneman, Daniela
    Karolinska Inst, Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Drevin, Linda
    Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
    Correlation of Gleason Score in Biopsy and Radical Prostatectomy Specimens 2000-2012-A Registry Study of 15598 Men2015Ingår i: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 95, s. 217A-218AArtikel i tidskrift (Övrigt vetenskapligt)
  • 85. Egevad, Lars
    et al.
    Kristiansen, Anna
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Prognostic Significance of Prostate Cancer with Seminal Vesicle Invasion on Radical Prostatectomy: A National Registry Study2017Ingår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 30, nr Suppl. 2, s. 222A-222A, artikel-id 896Artikel i tidskrift (Övrigt vetenskapligt)
  • 86. Egevad, Lars
    et al.
    Kristiansen, Anna
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Prognostic Significance of Prostate Cancer with Seminal Vesicle Invasion on Radical Prostatectomy: A National Registry Study2017Ingår i: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 97, s. 222A-222AArtikel i tidskrift (Refereegranskat)
  • 87. Fall, Katja
    et al.
    Garmo, Hans
    Regional Oncological Center, Uppsala University.
    Andrén, Ove
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Adolfsson, Jan
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Prostate-specific antigen levels as a predictor of lethal prostate cancer2007Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 99, nr 7, s. 526-532Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer. METHODS: To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided. RESULTS: During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at baseline (P = .05) and the rate of PSA change (P<.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level. CONCLUSIONS: Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting.

  • 88.
    FitzGerald, L. M.
    et al.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic 3004, Australia;Univ Tasmania, Menzies Inst Med Res, Canc Genet & Immunol, Hobart, Tas 7001, Australia.
    Zhao, S.
    NIEHS, Biostat & Computat Biol Branch, Res Triangle Pk, NC 27709 USA.
    Leonardson, A.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Geybels, M. S.
    Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Dept Epidemiol, NL-6211 LK Maastricht, Netherlands;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Kolb, S.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Lin, D. W.
    Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Wright, J. L.
    Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Eeles, R.
    Royal Marsden Natl Hlth Serv Fdn Trust, London, England;Royal Marsden Natl Hlth Serv Fdn Trust, Sutton SW3 6JJ, Surrey, England;Inst Canc Res, Sutton SM2 5NG, Surrey, England.
    Kote-Jarai, Z.
    Inst Canc Res, Sutton SM2 5NG, Surrey, England.
    Govindasami, K.
    Inst Canc Res, Sutton SM2 5NG, Surrey, England.
    Giles, G. G.
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Carlton, Vic 3053, Australia;Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic 3004, Australia.
    Southey, M. C.
    Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3010, Australia.
    Schleutker, J.
    Turku Univ Hosp, Dept Med Genet, Tuch Microbiol & Genet, Turku 20520, Finland;Univ Turku, Dept Med Biochem & Genet, Inst Biomed, Turku 20014, Finland.
    Tammela, T. L.
    Tampere Univ Hosp, Dept Urol, Tampere 33521, Finland;Univ Tampere, Prostate Canc Res Ctr, Sch Med, Tampere 33100, Finland.
    Sipeky, C.
    Univ Turku, Dept Med Biochem & Genet, Inst Biomed, Turku 20014, Finland.
    Penney, K. L.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA;Brigham & Womens Hosp, Dept Med, Charming Div Network Med, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Stampfer, M. J.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA;Brigham & Womens Hosp, Dept Med, Charming Div Network Med, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Gronberg, H.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
    Wiklund, F.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci, S-90187 Umea, Sweden.
    Hugosson, J.
    Univ Goteborgs, Inst Clin Sci, Dept Urol, S-40530 Goteborgs, Sweden.
    Karyadi, D. M.
    NHGRI, NIH, Bethesda, MD 20854 USA.
    Ostrander, E. A.
    NHGRI, NIH, Bethesda, MD 20854 USA.
    Feng, Z.
    MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
    Stanford, J. L.
    Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases2018Ingår i: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 21, nr 2, s. 228-237Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed.

    Methods: Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach.

    Results Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 x 10(-2)) and IL4 (rs2070874; HR 1.22; p-value = 1.1 x 10(-3)) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 x 10(-2)).

    Conclusions: This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.

  • 89.
    Forsberg, Ole
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Carlsson, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Ullenhag, Gustav
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Tötterman, Thomas H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Essand, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    High frequency of prostate antigen-directed T cells in cancer patients compared to healthy age-matched individuals2009Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 69, nr 1, s. 70-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND. In order to obtain a sustained cytotoxic T lymphocyte (CTL) response against cancer cells it is preferable to have CTLs directed against multiple peptide epitopes from numerous tumor-associated antigens.

    METHODS. We used a flow cytometry-based interferon (IFN)-g secretion assay to analyze whether CD8+ T cells directed against any of 24 HLA-A*0201-binding peptides from 15 prostate-associated proteins can be found in the peripheral blood of patients with localized prostate cancer. We also investigated whether multiple prostate antigen-specific CD8+ T cells can be generated simultaneously, from a naïve T cell repertoire. In that case, dendritic cells (DCs) from peripheral blood of healthy donors were divided in six portions and separately pulsed with six peptides. The peptide-pulsed DCs were then pooled and used to stimulate autologous T cells. The T cells were re-stimulated with peptide-pulsed monocytes.

    RESULTS. We found prostate antigen-restricted CD8+ T cells in the peripheral blood in 48 out of 184 (26.1%) analyzed samples from 25 cancer patients. This is significantly higher than 17 out of 214 analyzed samples (7.9%) from 10 healthy age-matched male individuals (p = 0.0249). In the cases when antigen-specific T cells could not be detected, we were able to generate IFN-g-producing CD8+ T cells specific for up to three prostate antigens simultaneously from a naïve T cell repertoire.

    CONCLUSIONS. CD8+ T cells directed against prostate antigen peptides can be found in, or generated from, peripheral blood. This indicates that such T cells could be expanded ex vivo for adoptive transfer to prostate cancer patients.

  • 90.
    Fortin, Marc-André
    et al.