Peter Iversen

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (129)419.4 Total impact

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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.
    Biomarkers in Medicine 03/2015; 9(4):319-26. DOI:10.2217/bmm.14.74 · 2.86 Impact Factor
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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.
    European Urology 02/2015; 65. DOI:10.1016/j.eururo.2015.01.027 · 12.48 Impact Factor
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    ABSTRACT: 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.
    12/2014; DOI:10.3109/21681805.2014.984324
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    ABSTRACT: 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.
    11/2014; DOI:10.3109/21681805.2014.970572
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    ABSTRACT: Background Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed. Objective To examine the association between ERG expression at diagnosis and the risk of progression during AS. Design, setting, and participants This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10–12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression. Outcome measurements and statistical analysis Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events. Results and limitations A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p < 0.0001) and of the subgroups PSA progression (p < 0.0001) and histopathologic progression (p < 0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3–29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7–68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62–3.72; p < 0.0001). The main limitation of this study is its observational nature. Conclusions In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes. Patient summary The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression.
    European Urology 11/2014; 66(5). DOI:10.1016/j.eururo.2014.02.058 · 12.48 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
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    ABSTRACT: To investigate the clinical implications of interobserver variation in the assessment of re-biopsies obtained during active surveillance (AS).
    BJU International 06/2014; DOI:10.1111/bju.12820 · 3.13 Impact Factor
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    ABSTRACT: Background Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. Methods In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. Results The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment. Conclusions Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.)
    New England Journal of Medicine 06/2014; 371(5). DOI:10.1056/NEJMoa1405095 · 54.42 Impact Factor
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    ABSTRACT: To investigate how location of positive surgical margins (PSM) in pT2 tumors affect the risk of biochemical recurrence (BR). The study includes 1,133 consecutive patients from 1995 until end of 2011, who had organ-confined disease (pT2) following RP. The location of PSM was stratified into apical and non-apical. BR was defined as the first PSA ≥ 0.2 ng/ml after RP. Risk of BR was analyzed with Kaplan-Meier and Cox regression analysis. Median follow-up was 3.6 years (range: 0.5-15.5 years). The overall pT2 PSM rate was 26.3%. Overall, a pT2 with PSM had a 3.1-fold increased risk of BR compared to margin negative patients. Patients with pT2 apical and non-apical PSM had a 5-year biochemical recurrence-free survival of 84.9% (95% CI: 77.6-92.2%) and 78.6% (95% CI: 71.3-85.9%), respectively. In multivariate analysis, pT2 apical and non-apical PSM was individually associated with a 2.2- and 3.8-fold increased risk of BR compared to margin negative patients. In our cohort the location of pT2 PSM was associated with time to BR, that is, patients with non-apical pT2 PSM endured the highest risk of BR compared to apical PSM. This may indicate that not all patients with pT2 PSM should be offered adjuvant therapy. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 06/2014; 109(8). DOI:10.1002/jso.23573 · 2.84 Impact Factor
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    ABSTRACT: Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection for the AS strategy and how they should be managed within the program. However, uncertainties persists concerning optimal patient selection and reliable progression criteria, as well as the long-term safety of AS. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 06/2014; 109(8). DOI:10.1002/jso.23584 · 2.84 Impact Factor
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    ABSTRACT: INTRODUCTION AND OBJECTIVES: Enzalutamide (ENZA), an oral androgen receptor inhibitor, improved overall survival (OS) in mPC patients (pts) who had received prior docetaxel (Scher et al, NEJM 367:13, 2012). The PREVAIL study examined the impact of ENZA on OS and radiographic progression-free survival (rPFS) in asymptomatic or mildly symptomatic chemotherapy-naïve men with mPC that had progressed on androgen deprivation therapy (ADT). Based on statistically significant benefits for ENZA in OS and rPFS, the Data Monitoring Committee recommended stopping the study at the interim analysis. Here we report primary endpoint results and subgroup analyses of pts with and without visceral disease defined as liver and/or lung metastases. METHODS: In this double-blind, multinational study, pts were randomized 1:1 to ENZA 160 mg/day or placebo. OS and rPFS were coprimary endpoints. Planned sample size was 1680 with 765 deaths to achieve 80% power to detect a target OS hazard ratio (HR) of 0.815 with a 2-sided type I error rate of 0.049 and a single interim analysis at 516 (67%) deaths. Prespecified subgroup analyses evaluated OS and rPFS in pts with and without visceral disease and followed the same statistical methodologies as the protocol-specified analyses for all pts. Additional subgroup analysis of time to cytotoxic chemotherapy, a key secondary endpoint, was performed post hoc. RESULTS: A total of 1717 men were randomized (1715 treated), including 1513 pts (88.1%) without and 204 (11.9%) with visceral disease at screening (63.7% lung and 36.3% liver and/or lung). Pts without visceral disease had lower baseline median PSA than pts with visceral disease (46.8 and 72.5 ng/mL, respectively), better performance status (68.9% and 61.8% ECOG PS ¼ 0), less lymph node disease (49.8% and 57.8%), but similar rates of bone disease (83.7% and 80.4%). OS, rPFS, and time to chemotherapy results by subgroup are shown in the table. CONCLUSIONS: Treatment with enzalutamide significantly improved OS and rPFS in men with chemotherapy-naïve mPC. Though pts with visceral disease progressed more rapidly regardless of treatment allocation, the benefit of enzalutamide was consistent among pts with or without visceral disease.
    The Journal of urology 05/2014; 191(4S):e223. DOI:10.1016/j.juro.2014.02.2577 · 3.75 Impact Factor
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    ABSTRACT: The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. 67 men were enrolled into the study. 62 patients (92·5%, 95% CI 86·2-98·8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer. Astellas Pharma Inc, Medivation Inc.
    The Lancet Oncology 04/2014; DOI:10.1016/S1470-2045(14)70129-9 · 24.73 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e768-e769. DOI:10.1016/j.juro.2014.02.2111 · 3.75 Impact Factor
  • European Urology Supplements 04/2014; 13(1):e345. DOI:10.1016/S1569-9056(14)60340-7 · 3.37 Impact Factor
  • European Urology Supplements 04/2014; 13(1):LBA3. DOI:10.1016/S1569-9056(14)61128-3 · 3.37 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e725. DOI:10.1016/j.juro.2014.02.1977 · 3.75 Impact Factor
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    ABSTRACT: Abstract Objective. The aim of this study was to describe recovery of urinary continence and potency and report oncological and functional outcomes using the survival, continence and potency (SCP) system for patients undergoing robot-assisted radical prostatectomy (RARP). Material and methods. From 2009 to 2012, 232 patients underwent RARP. Self-reported continence, erection sufficient for intercourse (ESI) and scores on the five-item version of the International Index of Erectile Function-5 (IIEF-5) were registered by questionnaire and physician's interview preoperatively and at 3, 6 and 12 month follow-up, and subsequently on a yearly basis. Continence was defined as 0 pads, and potency as ESI or IIEF-5 greater than 17 with or without the aid of phosphodiesterase type 5 inhibitors. Oncological success was defined as absence of biochemical failure (BF) [prostate-specific antigen (PSA) ≥0.2 ng/ml]. The SCP system was used to evaluate combined oncological and functional outcomes. Results. In total, 184 patients were followed for more than 1 year. The 12 month BF-free survival rate was 97.7%. Median time to regain continence was 6.2 months; 12 months postoperatively 79.9% used 0 pads/day. Of patients with preoperative ESI, 77.6% (67.9-86.1) and 34.4% (24.1-47.5) maintained ESI 12 months postoperatively after bilateral and unilateral nerve-sparing surgery (NS), respectively. NS (p < 0.0001), increasing prostate volume (p = 0.014) and lower age (p < 0.0001) were positively associated with recovery of potency. Using the SCP system and defining potency as ESI, functional and oncological success 12 months after surgery was achieved in 69 out of 135 (51.1%) preoperative continent and potent patients who underwent unilateral or bilateral NS, and did not require adjuvant treatment; when defining potency as IIEF greater than 17, this figure was 45 out of 108 (41.7%). As expected, the proportions were significantly higher for bilateral than for unilateral NS (p ≤ 0.0014). Conclusion. RARP provides good early BF-free survival, continence and potency recovery rates for patients eligible for NS.
    03/2014; 48(4). DOI:10.3109/21681805.2014.893534
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    ABSTRACT: To investigate risk factors associated with positive surgical margins (PSM) and biochemical recurrence (BR) in organ confined tumors (pT2) after radical prostatectomy (RP) for localized prostate cancer (PCa). Between 1995 and 2011, 1,649 patients underwent RP at our institution. The study includes the 1,133 consecutive patients with pT2 tumors at final histopathology. Logistic regression analysis was used for risk of PSM. Risk of BR, defined as the first PSA ≥ 0.2 ng/ml, was analyzed with Kaplan-Meier and Cox regression analysis. Median follow-up was 3.6 years (range: 0.5-15.5 years). In logistic regression, NS surgery was independently associated with an increased risk of pT2 PSM (OR = 1.68, 95% CI: 1.3-2.0, P = 0.01) relative to non-NS surgery. NS surgery was not independently associated with BR but the interaction of PSM and NS surgery trended (P = 0.08) to increase the risk of BR compared to PSM and non-NS surgery. Several factors influence the risk of pT2 PSMs in radical prostatectomy. In our cohort pT2 PSM is associated with NS surgery and trend to increase risk of BR compared to non-NS surgery. The optimal selection of candidates for NS surgery is still not clear. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 02/2014; 109(2). DOI:10.1002/jso.23469 · 2.84 Impact Factor
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    ABSTRACT: Abstract Objective.The aim of this study was to record prostate-specific antigen (PSA) response and overall survival (OS) for a group of metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide following progression after abiraterone treatment in the post-chemotherapy setting. Material and methods. Twenty-four mCRPC patients with progression after abiraterone treatment following primary docetaxel therapy received enzalutamide 160 mg/day. The percentage PSA response was recorded following first line docetaxel, abiraterone and enzalutamide treatment. Fischer's exact test, Mann-Whitney U test and linear regression model were used to test for differences in PSA response. Results.All patients had a follow-up of at least 3 months. The median PSA response following 1 month of enzalutamide was -12% (range -56% to 76%), while the median best PSA response was -22% (-76% to 76%). Forty-six percent had a greater than 30% decrease in PSA. The PSA response to enzalutamide did not correlate with the number of prior cancer treatments (p = 0.57), time from diagnosis to mCRPC (p = 0.11) or prior response to docetaxel (p = 0.67). However, patients treated with second line cabazitaxel had an inferior PSA response to enzalutamide (p = 0.03), and there was a trend for the PSA response to abiraterone to correlate with the PSA response to the succeeding enzalutamide (B = 0.22, p = 0.05). The median OS was 4.8 months. Conclusions.Previous abiraterone therapy is associated with a less marked fall in PSA following enzalutamide therapy in post-chemotherapy mCRPC patients compared with reported results in randomized trials. Larger prospective studies of sequencing are warranted.
    11/2013; DOI:10.3109/21681805.2013.860189
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    European Urology Supplements 11/2013; 12(6):152. DOI:10.1016/S1569-9056(13)62386-6 · 3.37 Impact Factor

Publication Stats

2k Citations
419.40 Total Impact Points

Institutions

  • 1998–2015
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2013–2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 1998–2013
    • Rigshospitalet
      • Department of Urology
      København, Capital Region, Denmark
  • 2000–2010
    • Walter Reed National Military Medical Center
      • Division of Urology
      Washington, Washington, D.C., United States
  • 2004
    • Technische Universität Dresden
      Dresden, Saxony, Germany
    • Herlev Hospital
      Herlev, Capital Region, Denmark
    • Medical College of Wisconsin
      • Department of Urology
      Milwaukee, Wisconsin, United States
  • 2002
    • Karolinska University Hospital
      • Department of Urology
      Tukholma, Stockholm, Sweden
  • 1997
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark