Peter Iversen

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (161)665.56 Total impact

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    ABSTRACT: Objectives: To investigate whether the International Society of Urological Pathology (ISUP) 2005 revision of the Gleason grading system has influenced the risk of biochemical recurrence (BR) after radical prostatectomy (RP), as the new guideline implies that some prostate cancers (PCa) previously graded as Gleason score (GS) 6 (3+3) are now considered as GS 7 (3+4). Patients and methods: A matched pair analysis was conducted. Two-hundred-and-fifteen patients with GS 6 or GS 7 (3+4) PCa on biopsies who underwent RP prior to December 31st, 2005 (pre-ISUP group), were matched 1:1 by biopsy GS, clinical tumour category, PSA, and margin status to patients undergoing RP between January 1st, 2008 and December 31st, 2011 (post-ISUP group). Patients were followed until BR defined as PSA ≥0.2 ng/ml. Risk of BR was analysed in a competing risk model. Results: Median follow-up was 9.5 years in the pre-ISUP group and 4.8 years in the post-ISUP group. The 5-year cumulative incidences of BR were 34.0% and 13.9% (p<0.0001) in the pre-ISUP and post-ISUP groups, respectively. The difference in cumulative incidence applied to both patients with GS 6 (p=0.0002) and GS 7 (3+4) (p=0.004). There was no difference in the 5-year cumulative incidence of BR between patients with pre-ISUP GS 6 and post-ISUP GS 7 (3+4) (p=0.34). In a multiple Cox-proportional hazard regression model, ISUP 2005 grading was a strong prognostic factor for BR within 5 years of RP (hazard ratio = 0.34; 95%CI: 0.22-0.54; p<0.0001). Conclusion: The revision of the Gleason grading system has reduced the risk of BR following RP in patients with biopsy GS 6 and 7 (3+4). This may have consequences when comparing outcomes across studies and historical periods and may affect future treatment recommendations. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · BJU International
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    ABSTRACT: Aim: Urokinase plasminogen activator receptor (uPAR) plays a central role during cancer invasion by facilitating pericellular proteolysis. We initiated the prospective 'Copenhagen uPAR Prostate Cancer' study to investigate the significance of uPAR levels in prostate cancer (PCa) patients. Methods: Plasma samples and clinical data from patients with newly diagnosed PCa have been collected prospectively. The uPAR forms have been measured in plasma using time-resolved fluorescence immunoassays. Results: The level of intact uPAR(I-III) did not differ. Plasma uPAR(I-III) + uPAR(II-III) levels and uPAR(I) levels were significantly higher in hormone-naive and castrate-resistant patients compared with patients with localized disease (both: p < 0.0001). Conclusion: Our results show that cleaved uPAR forms are significantly increased in patients with advanced PCa.
    No preview · Article · Jan 2016 · Biomarkers in Medicine
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    ABSTRACT: Background The prognostic value of PSA kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel), and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting.
    No preview · Article · Dec 2015 · Annals of Oncology
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    ABSTRACT: Background Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial.
    No preview · Article · Nov 2015 · Annals of Oncology
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    ABSTRACT: Aim: Physical activity after prostate cancer diagnosis has been shown to reduce the risk of disease progression. Here, we aimed to evaluate the effect of a 2-year home-based endurance training intervention on body composition, biomarkers levels, and prostate-specific antigen (PSA) doubling time as a surrogate end-point for progressing disease. Methods: Out-clinic patients with either biochemical recurrence following radical prostatectomy or patients managed on active surveillance were randomized to either 24 months (3 times/week) of home-based endurance training or usual care. Aerobic fitness, body composition, insulin sensitivity, and biomarkers were measured at 0, 6, and 24 months of intervention. PSA doubling time (PSADT) was calculated based on monthly PSA measurements. Results: Twenty-five patients were enrolled, and 19 patients completed the study. PSADT increased in the training group from 28 to 76 months (p < 0.05) during the first 6 months and was correlated with changes in VO2max (p < 0.01, r (2) = 0.41). The training group lost 3.6 ± 1.0 kg (p < 0.05) exclusively as fat mass, yet the changes in body composition were not associated with the increased PSADT. The training group showed significant improvements in plasma triglycerides, adiponectin, IGF-1, IGFBP-1, and fasting glucose levels, but no changes in insulin sensitivity (measured as Matsuda index), testosterone, cholesterols, fasting insulin, plasma TNF-alpha, IL-6, or leptin levels. The control group showed no changes in any of the evaluated parameters across the 2-year intervention. Conclusion: In this small randomized controlled trial, we found that improvements in fitness levels correlated with increasing PSADT, suggesting a link between training and disease progression.
    No preview · Article · Nov 2015 · Cancer Causes and Control
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    ABSTRACT: Background: Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality. Methods: We conducted a case-control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man's number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies. Results: The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03). Conclusions: We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.
    Full-text · Article · Sep 2015 · Cancer Causes and Control
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    ABSTRACT: We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. ERG expression was assessed by immunohistochemistry (IHC) in 625 biopsy sets and 86 radical prostatectomy specimens from 265 patients with prostate cancer managed on active surveillance. For IHC, a rabbit monoclonal primary antibody was used (clone: EPR3864). TMPRSS2-ERG fluorescence in situ hybridisation (FISH) analyses were performed in 74 biopsies using the FISH ZytoLight TriCheck Probe (SPEC ERG/TMPRSS2). FISH results were correlated with IHC findings. The concordance between FISH and IHC was 97.3% and IHC demonstrated a sensitivity and specificity for ERG rearrangement of 100% and 95.5%, respectively. Applying IHC, 38.1% of patients were ERG-positive, 53.6% were ERG-negative and 8.3% showed both ERG-positive and negative tumour foci (ERG heterogeneous) at diagnosis. When ERG status was dichotomised (ERG-positive or heterogeneous vs ERG-negative), 95.6%-97.1% of patients did not experience ERG reclassification during the first two rounds of rebiopsies. The concordance in ERG status between biopsies and surgical specimen was 89.5%-94.2% depending on the number of rebiopsies included. Sampling bias was assumed to explain most (81.3%) of the mismatches in ERG status. Consistency in ERG status ranged from 90% to 95% for patients undergoing serial biopsies and radical prostatectomy. This indicates that biopsies can be used reliably to investigate ERG's prognostic and predictive value. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · Jun 2015 · Journal of Clinical Pathology
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    ABSTRACT: Castration-resistant prostate cancer (CRPC) is defined as tumour progression despite castrate levels of serum testosterone. During the past decade a number of new therapies, including chemotherapy and novel endocrine agents have been approved for CRPC treatment. The continued need for new effective drugs in CRPC has led to development of a novel therapeutic approach in CRPC treatment. Therapeutic vaccines activate the immune system to kill prostate cancer cells. This review describes recent pivotal phase 2 and 3 trials of CRPC vaccines and discusses the impact on future CRPC management.
    No preview · Article · May 2015 · Ugeskrift for laeger
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    ABSTRACT: Background Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC.Methods In total, 194 patients with advanced and/or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified on ERG-status. Risk reclassification and time-dependent area under the ROC curves were used to assess the discriminative ability of ERG-status. Time to PSA-nadir, proportion achieving PSA-nadir ≤0.2 ng/ml, and risk of PCa-specific death were secondary endpoints.ResultsMedian follow-up was 6.8 years (IQR: 4.9–7.3). In total, 105 patients (54.1%) were ERG-positive and 89 (45.9%) were ERG-negative. No difference in risk of CRPC was observed between ERG subgroups (P = 0.51). Median time to CRPC was 3.9 years (95%CI: 3.2–5.1) and 4.5 years (95%CI: 2.3-not reached) in the ERG-positive and ERG-negative group, respectively. Compared to a model omitting ERG-status, the ERG-stratified model showed comparable AUC values 1 year (77.6% vs. 78.0%, P = 0.82), 2 years (71.7% vs. 71.8%, P = 0.85), 5 years (68.5% vs. 69.9%, P = 0.32), and 8 years (67.9% vs. 71.4%, P = 0.21) from ADT initiation. No differences in secondary endpoints were observed.ConclusionsERG expression was not associated with risk of CRPC suggesting that ERG is not a candidate biomarker for predicting response to primary ADT in patients diagnosed with advanced and/or metastatic PCa. Prostate © 2015 Wiley Periodicals, Inc.
    Full-text · Article · May 2015 · The Prostate
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    ABSTRACT: The objective of this study was to investigate the association between active surveillance (AS) progression criteria and histopathology features in subsequent radical prostatectomy (RP) specimens. Of 229 patients managed on AS, 80 patients underwent RP, of whom 68 met at least one of the following three progression criteria: progression on rebiopsy, short prostate-specific antigen (PSA) doubling time (PSAdt) and increase clinical tumour category (cT). Patients revealing histopathological features in the RP specimens involving GS ≥ 7 (3 + 4) were considered to have achieved a potential survival gain from the procedure (timely RP). The association between the progression criteria and timely RP was analysed using univariate logistic regression analyses. Of the 68 patients who met at least one of the progression criteria, 66% had timely RP features. Progression on rebiopsy was significantly associated with timely RP [odds ratio (OR) = 5.00, 95% confidence interval (CI) 1.51-16.51]. Although not statistically significant, progression defined by PSAdt was negatively associated with timely RP (OR = 0.36, 95% CI 0.13-1.00). Increase in cT showed no association with timely RP (OR = 1.17, 95% CI 0.35-3.87). A poor association was found between the progression criteria employed in the AS programme and histopathology features after subsequent RP. Only progression on rebiopsy was significantly associated with final histopathology.
    Full-text · Article · Apr 2015 · Scandinavian Journal of Urology
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    ABSTRACT: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p=0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR=1.19 (95% CI: 1.00-1.43), p=0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care (n=991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment. Throughout the 14.6year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · European journal of cancer (Oxford, England: 1990)

  • No preview · Article · Apr 2015 · European Urology Supplements

  • No preview · Article · Apr 2015 · European Urology Supplements

  • No preview · Article · Apr 2015 · European Urology Supplements

  • No preview · Conference Paper · Mar 2015
  • Solvej Lippert · Peter Iversen · Klaus Brasso · Jens P Goetze
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    ABSTRACT: Seminal plasma offer a more organ-specific matrix for markers in prostatic disease. We hypothesized that C-type natriuretic peptide (CNP) expression may constitute such a new target. Patients with benign prostatic hyperplasia, clinically localized and metastatic prostate cancer were examined for CNP and CNP precursor (proCNP) concentrations in blood and seminal plasma. Furthermore, CNP and the CNP receptor (NPR-B) mRNA contents in tissue from prostate and seminal vesicles were analyzed by qPCR. CNP and NPR-B concentrations decreased with increasing tumor burden (p = 0.0027 and p = 0.0096, respectively). In contrast, seminal plasma CNP and proCNP concentrations were markedly increased with increased tumor burden (p < 0.0001 and p < 0.0001, respectively). CNP/proCNP could be new markers in human prostate cancer.
    No preview · Article · Mar 2015 · Biomarkers in Medicine
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    ABSTRACT: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. Open-label, single-arm study in patients with HNPC and noncastrate testosterone (≥230 ng/dl). Oral enzalutamide 160mg/d until disease progression or unacceptable toxicity. PSA response (≥80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk). The median (range) age was 73 (48-86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92-100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk. Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD. In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naïve prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. NCT01302041. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · European Urology
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    ABSTRACT: Objective: The aim of this study was to analyse relative survival, excess mortality and gain in life expectancy in men who underwent radical prostatectomy (RP) for localized prostate cancer (PCa) between 1995 and 2011 in Denmark. Material and methods: The study population comprised the complete cohort of 6489 men who underwent RP between 1995 and 2011. Risk of mortality was calculated using a competing risk model. Relative survival, excess mortality rate (EMR) and gain in life expectancy in men undergoing RP were calculated using a matched cohort Danish population based on date of birth and date of surgery. Results: During follow-up 328 patients died, 109 (33.2%) of PCa and 219 (66.8%) of other causes. The cumulative incidence of PCa mortality was 5.8% [95% confidence interval (CI) 4.4, 7.2] after 10 years. Relative survival was significantly above 1.0 for RP patients, except for high-risk patients. EMR was -9.34 (95% CI -10.56, -8.13) after 10 years, i.e. nine men would die in excess of the general population. Overall, the gain in life expectancy in men undergoing RP compared with the general population was 0.41 years. Conclusion: This population-based study demonstrated that the gain in life expectancy with RP compared with the general population in Denmark is minimal.
    No preview · Article · Dec 2014 · Scandinavian Journal of Urology
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    ABSTRACT: Objective: Evidence supports active surveillance (AS) as a means to reduce overtreatment of low-risk prostate cancer (PCa). The consequences of close and long-standing follow-up with regard to outpatient visits, tests and repeated biopsies are widely unknown. This study investigated the trajectory and costs of AS in patients with localized PCa. Materials and methods: In total, 317 PCa patients were followed in a prospective, single-arm AS cohort. The primary outcomes were number of patient contacts, prostate-specific antigen (PSA) tests, biopsies, hospital admissions due to biopsy complications and patients eventually undergoing curative treatment. The secondary outcome was cost. Results: The 5 year cumulative incidence of discontinued AS in a competing-risk model was 40%. During the first 5 years of AS patients underwent a median of two biopsy sets, and patients were seen in an outpatient clinic including PSA testing three to four times annually. In total, 38 of the 406 biopsy sessions led to hospital admission and 87 of the 317 patients required treatment for bladder outlet obstruction (BOO). With a median of 3.7 years' follow-up, the total cost of AS was euro (€) 1,240,286. Assuming all patients had otherwise undergone primary radical prostatectomy, the cost difference favoured AS with a net benefit of €662,661 (35% reduction). Conclusions: AS entails a close clinical follow-up with a considerable risk of rebiopsy complication, treatment of BOO and subsequent delayed definitive therapy. This risk should be weighed against a potential economic benefit and reduction in the risk of overtreatment compared to immediate radical treatment.
    Full-text · Article · Nov 2014 · Scandinavian Journal of Urology
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    Full-text · Article · Nov 2014 · European Urology Supplements

Publication Stats

3k Citations
665.56 Total Impact Points

Institutions

  • 1998-2015
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2013-2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
    • Copenhagen Trial Unit
      København, Capital Region, Denmark
  • 2007-2014
    • Herlev Hospital
      Herlev, Capital Region, Denmark
  • 2006-2013
    • Rigshospitalet
      • Department of Urology
      København, Capital Region, Denmark
  • 2004
    • Medical College of Wisconsin
      • Department of Urology
      Milwaukee, Wisconsin, United States
  • 2002
    • Karolinska University Hospital
      • Department of Urology
      Tukholma, Stockholm, Sweden
  • 1997
    • Næstved Hospital
      Нествед, Zealand, Denmark