Axel Heidenreich

RWTH Aachen University, Aachen, North Rhine-Westphalia, Germany

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Publications (601)2256.58 Total impact

  • A Heidenreich · M Braun · M Oelcke · J Salem · H Schwaibold · R Berges · P.J. Goebell
    Der Urologe 08/2015; 54(8):1094-6. DOI:10.1007/s00120-015-3884-2 · 0.44 Impact Factor
  • C Parker · S Gillessen · A Heidenreich · A Horwich
    Annals of Oncology 07/2015; 26 Suppl 5. DOI:10.1093/annonc/mdv222 · 7.04 Impact Factor
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    ABSTRACT: Positive surgical margins (PSM) after radical prostatectomy have been shown to be associated with impaired outcome. In pT3pN0 patients with PSM either immediate radiotherapy or clinical and biological monitoring followed by salvage radiotherapy is recommended by the latest guidelines of the European Association of Urology. A retrospective, multicenter study of eight urological centers was conducted on 536 prostatectomy patients with pT3aN0/NxR1 tumors and no neoadjuvant/adjuvant therapy. A pathological re-review of all prostate specimens was performed. Association of clinical and pathological features with biochemical recurrence (BCR) was analyzed using univariate and multivariate analysis. With 48months median follow-up, BCR occurred in 39.7%. Preoperative PSA value, performance of pelvic lymph node dissection and Gleason score were significantly associated with BCR. In multivariate analysis, Gleason score was the only independent prognostic factor (p<0.001) for BCR. Five-year BCR-free survival rates were 74%, 70%, 38%, and 51% with Gleason score 6, 3+4=7a, 4+3=7b, and 8-10, respectively. In pT3aN0/NxR1 patients with no adjuvant/neoadjuvant treatment, Gleason Score permits independent prediction of the risk for BCR. These findings could help to estimate and discuss the individual risk for BCR with our patients on an individual basis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 06/2015; 116:119-124. DOI:10.1016/j.radonc.2015.06.021 · 4.36 Impact Factor
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    ABSTRACT: High-intensity focused ultrasound (HIFU) is a technology to ablate prostate cancer.The next generation Focal One® device has been used at various prostate cancer centers in Europe since 2014. It displays substantial improvements: fusion of multiparametric MRI (mpMRI) and transrectal ultrasound (TRUS) images, doubled lesion height enabling treatment of larger glands, dynamic focusing and intraoperative effectiveness monitoring by contrast-enhanced ultrasound. Precise treatment area contouring within the gland for focal therapy has now become easier. This study describes results obtained in patients treated with Focal One® at 6 German centers and Zürich. A total of 140 HIFU treatments were performed: 80 as focal/partial therapy (28 x Hemiabladation), 42 as whole-gland therapy and 18 as salvage therapy (9 after percutaneous radiotherapy, 6 after LDR brachytherapy and three after primary HIFU). Transurethral resection of the prostate was performed in 45 patients before and one patient after HIFU (33%). 84 (60%) patients received pretreatment mpMRI and 47 MRI of the pelvis. The average length of hospital stay was 3 days (average and median; 2-13). The indwelling catheter use was 2,1 days in the average.There were no complications of the rectum but two cases of incontinence grade I. Other complications occurred in 16 cases (3 x Clavien grade I, 12 x Clavien grade 2, 1 x Clavien grade 3 (TUR-P 2 weeks after HIFU)). On the other hand, 65 % of the patients were completely free of subjective complaints after treatment. In the group of focal treated patients the Gleason Score was 6 (Median; 43 x 6, 25 x 7a, 8 x 7b,1 x 8, 3 x 9), psa was 6.4ng/ml in the average. The clinical stage was cT3 in one and cT2a in 9 of the focally treated patients, cT1c in the others. Through markedly improved technology, the next generation Focal One® device goes beyond the scope of hitherto standard HIFU treatments (primary whole-gland treatment and salvage after radiotherapy) to enable much more precise, less traumatic and now also focal treatment. The new procedure has a remarkably low morbidity compared to previous generations of devices. For an assessment of oncological outcome and possible late complications the Follow-up is still too short. Pretreatment transurethral resection was rarely required.
    8th International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer, Noordwijk, The Netherlands; 06/2015
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    ABSTRACT: The first St.Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection.Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with advanced prostate cancer in clinical trials should be encouraged. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
    Annals of Oncology 06/2015; 26(8). DOI:10.1093/annonc/mdv257 · 7.04 Impact Factor
  • Axel Heidenreich
    BJU International 06/2015; 115(6):849-50. DOI:10.1111/bju.12995 · 3.53 Impact Factor
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    ABSTRACT: Baclground: Point mutations and small insertions/deletions (indels) in tumor relevant genes have been identified and proposed as new indicators of prognostic subsets in molecular pathology. Next generation sequencing (NGS) technologies provide the simultaneous analysis of genomic mutations in numerous target regions with high sensitivity. In the present study, multiplex PCR combined with NGS was used to establish a robust, low cost, and high sensitivity pipeline to analyse mutations of diagnostic relevant genes in prostate cancer with therapy resistance and metastases. Material & Methods: A total of more than 100 formalin-fixed and paraffin-embedded (FFPE) prostate cancer tissues including primary prostate carcinoma and the corresponding metastases, as well as prostate carcinoma from patients with transurethral resection or salvage therapy, were used for tumore macrodissection and automated DNA extraction. DNA was quantified by GeneRead quantitative PCR (Qiagen, Hilden GER) and cancer related gebe loci were amplified by multiplex PCR using primer sets designed and provided by Qiagen according to recent literature of whole exome sequencing reports. Specific barcode adapters were ligated and adapter library pools of each sample were sequenced using a MiSeq intrument platform (Illumina). Conventional Sanger sequencing served as a referenece technology. Primary data analysis and generation of fastq files was carried out by means of the MiSeq reporter program. Alignment and variant calling was performed using the CLC Cancer Workbench software (CLCbio, Qiagen). Results: We obtained a total of around 10 million reads per run. Each of the 1,837 amplicons was covered by 400 to 2,000 reads. After seperation of known single nucleotide polymorphisms (SNPs), silent mutations, and aberrations with allelic fraction <5%, mutation hotpsots in many of the 31 tumor specific genes were identified. Frequent mutations were found in TP53, the androgen receptor gene, in the epigenetic writer MLL2, as well as in the MED12 and PIK3CA genes. Conclusions: We established an easy to use, low cost, and fast pipeline of mutation analysis of a prostate cancer specific, hotspot gene panel covering the diagnostic relevant loci by a deep and highly reproducible coverage.
    99. Jahrestagung der deutschen Gesellschaft für Pathologie, Frankfurt/Main; 05/2015
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    Alexandra Kienel · Daniel Porres · Axel Heidenreich · David Pfister
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    ABSTRACT: Chemotherapy is an integral part in the treatment of castration resistant prostate cancer (CRPC). With the introduction of new drugs the need of identifying non responder is increasing. Till now there are no prognostic parameters with the initiation of any treatment. CfDNA was isolated from serum specimen before chemotherapy. Its value was correlated to recurrence-free and overall survival using Kaplan-Meier Curves. Uni- and multivariate Cox regression analysis had been performed for identifying independent predictors. 48 (81.4 %) of 59 men, had a measurable PSA decrease from PSA baseline. The median follow-up was 15.0 (2.4-58.4) months. The median cfDNA concentration from all men in this study was 27.71 ng/ml (mean 32.64 ng/ml). A threshold of 55,03ng/ml was significantly associated with a poor PSA resonse <30% (p=0.005). In a univariate and multivariate analysis, cell-free circulating DNA was an independent predictor for overall survival (UV: hazard ratio 0.36; 95 % confidence interval, 0.13-0.97; p=0.044; MV: hazard ratio 0.34; 95 % confidence interval, 0.12-0.91; p=0.032). Limitation of the study is its retrospective character as well as first- and second-line therapies. In our trial, cfDNA concentration before therapy may be a useful predictive and prognostic biomarker for PSA response and survival. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of urology 04/2015; 193(4). DOI:10.1016/j.juro.2015.04.055 · 4.47 Impact Factor
  • Axel Heidenreich · David Pfister
    Nature Reviews Urology 04/2015; 12(5). DOI:10.1038/nrurol.2015.81 · 4.84 Impact Factor
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    Axel Heidenreich · David Pfister
    04/2015; 9(3-4):232. DOI:10.5489/cuaj.2877
  • A. Heidenreich · D. Porres · D. Pfister
    European Urology Supplements 04/2015; 14(2):e601. DOI:10.1016/S1569-9056(15)60594-2 · 3.37 Impact Factor
  • The Journal of Urology 04/2015; 193(4):e496. DOI:10.1016/j.juro.2015.03.084 · 4.47 Impact Factor
  • A. Heidenreich · D. Porres · T. Kuru · D. Pfister
    European Urology Supplements 04/2015; 14(2):e1018. DOI:10.1016/S1569-9056(15)61006-5 · 3.37 Impact Factor
  • Julius van Essen · David Pfister · Axel Heidenreich
    03/2015; 02(01):43-55. DOI:10.1055/s-0034-1391396
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    ABSTRACT: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.
    World Journal of Urology 02/2015; 33(7). DOI:10.1007/s00345-015-1510-y · 2.67 Impact Factor
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    ABSTRACT: Histological tumor subtyping, staging, and grading are of utmost importance to stratify patients with bladder cancer for treatment and should be as precise as possible. In the presented study, we investigated the prognostic impact of standard clinicopathological parameters in cystectomy patients and compared embedding of the entire bladder with standard partial embedding via a virtual superimposed approach. The study included 121 cystectomy specimens, which were completely embedded. Clinical and histopathological data of patients were obtained (median follow-up 21.5 months; range 1-67 months). For 88 patients two-dimensional tumor maps (macrophotographs and histology-based maps) were prepared, and embedding of the entire bladder was compared with a virtual standard partial embedding, created by a virtual overlay and data extraction of the tumor maps. Kaplan-Meier plots, Cox regression estimators, Chi-square, and McNemar tests were used. In a multivariate Cox regression model for overall survival, only venous invasion (p = 0.008, HR = 3.35, 95 % CI 1.375-8.161) and organ-confined (pTis-pT2) versus non-organ-confined diseases (pT3-pT4; p = 0.021, HR 2.669, 95 % CI 1.157-6.159) were found significant. Advanced versus standard embedding revealed significant improvement in the detection of carcinoma in situ (50 versus 61, p = 0.003) and lymphatic invasion (18 versus 24, p = 0.041), but no significant advantage in the detection of tumor stage, tumor multifocality, or venous invasion (all p > 0.05). TNM classification, including lymphatic and venous invasion, is of utmost importance to stratify patients with advanced invasive bladder cancer. Histopathological details are detected more reliably by whole organ embedding, but this approach showed no significant benefit in terms of outcome-related parameters (max. tumor stage, venous invasion) in our cohort.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2015; 466(4). DOI:10.1007/s00428-015-1726-7 · 2.65 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 · 13.94 Impact Factor
  • D Pfister · D Porres · V Matveev · A Heidenreich
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    ABSTRACT: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is associated with complications and decreased adjunctive surgery. Little data are available concerning PC-RPLND in patients with advanced seminomas and residual retroperitoneal tumor lesions. We examined intra- and postoperative complications as well as the frequency of adjunctive surgeries in patients with seminoma and compared the data to a cohort of patients with non-seminomatous germ cell tumors (NSGCT) who underwent PC-RPLND. In our retrospective analysis, 580 patients (43 patients with advanced seminomas and 537 patients with NSGCT) underwent PC-RPLND between 1989 and 2010. The surgical approach was preferred via midline incision or a thoracoabdominal approach depending on the location of the residual tumor. Of the 43 patients with seminoma, a total number of 13 adjunctive surgeries were performed in 7 patients. There were only three intraoperative complications, two postoperative complications (prolonged intestinal paralyses). There were no significant differences in adjunctive surgeries and postoperative complications (p=0.49 and p=0.133) between the two groups. There were significantly fewer intraoperative complications in favor of seminomas (p=0.001). PCRLND in seminomas and NSGCT is a demanding surgical intervention. In contrast to other series we did not find significant differences in the two patient groups concerning adjunctive surgeries and postoperative complications. The indication for PCLND in patients with seminoma is limited, but if necessary it can be performed safely in experienced centers.
    Der Urologe 01/2015; DOI:10.1007/s00120-014-3708-9 · 0.44 Impact Factor
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    ABSTRACT: This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 (P < 0.044) in prostate cancer, while vinculin showed significant upregulation (P < 0.001). Secernin-1 overexpression in prostate tissue was validated using Western blot and immunohistochemistry while vinculin expression was validated using immunohistochemistry. These findings indicate that secernin-1 and vinculin are potential new tissue biomarkers for prostate cancer diagnosis and prognosis, respectively. For validation, protein levels in urine were also examined by Western blot analysis. Urinary vinculin levels in prostate cancer patients were significantly higher than in urine from nontumor patients (P = 0.006). Using multiple reaction monitoring-MS (MRM-MS) analysis, prostatic acid phosphatase (PAP) showed significant higher levels in the urine of prostate cancer patients compared to controls (P = 0.012), while galectin-3 showed significant lower levels in the urine of prostate cancer patients with biochemical relapse, compared to those without relapse (P = 0.017). Three proteins were successfully differentiated between patients with and without prostate cancer and patients with and without relapse by using MRM. Thus, this technique shows promise for implementation as a noninvasive clinical diagnostic technique.
    BioMed Research International 01/2015; 2015:454256. DOI:10.1155/2015/454256 · 3.17 Impact Factor
  • A Heidenreich · D Pfister · B Brehmer · D Porres
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    ABSTRACT: Androgen deprivation therapy (ADT) represents the standard treatment for patients with prostate cancer (PCA) and osseous metastases. We explored the role of cytoreductive radical prostatectomy in PCA with low volume skeletal metastases in terms of a feasibility study. A total of 23 patients with biopsy proven PCA, minimal osseous metastases (≤3 hot spots on bone scan), absence of visceral or extensive lymph node metastases and a decrease in prostate-specific antigen (PSA) to <1.0 ng/ml after neoadjuvant ADT were included in the feasibility study (group A). The control group (group B) consisted of 38 men with metastatic PCA who were treated by ADT alone. Surgery-related complications, time to castration resistance, symptom-free, cancer-specific and overall survival were analyzed using descriptive statistical analyses. The mean age was 61 years (range 42-69 years) and 64 years (47-83) in groups A and B, respectively, with similar patient characteristics in terms of initial PSA level, biopsy Gleason score, clinical stage and extent of metastatic disease. The median follow-up was 34.5 months (7-75 months) and 47 months (28-96 months) in groups A and B, respectively. Median time to castration resistance was 40 months (9-65 months) and 29 months (16-59 months) in groups A and B, respectively (p=0.04). Patients in group A experienced significantly better clinical symptom-free (38.6 versus 26.5 months, p=0.032) and cancer-specific survival rates (95.6% versus 84.2%, p=0.043) whereas the overall survival was similar. In group A none of the men underwent palliative surgical procedures for locally progressing PCA compared to 29% in group B. Cytoreductive radical prostatectomy is feasible in well-selected men with metastatic PCA who responded well to neoadjuvant ADT. These men have a long life expectancy and the risk of locally recurrent PCA and local complications are reduced. Cytoreductive radical prostatectomy might be a treatment option in the multimodal management of PCA with minimal osseous metastases.
    Der Urologe 12/2014; 54(1). DOI:10.1007/s00120-014-3697-8 · 0.44 Impact Factor

Publication Stats

11k Citations
2,256.58 Total Impact Points


  • 2009–2015
    • RWTH Aachen University
      • Department of Urology
      Aachen, North Rhine-Westphalia, Germany
    • University Medical Center Hamburg - Eppendorf
      Hamburg, Hamburg, Germany
  • 2005–2015
    • University Hospital RWTH Aachen
      Aachen, North Rhine-Westphalia, Germany
  • 2008–2012
    • Universitätsklinikum Düsseldorf
      • Urologische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
    • Heinrich-Heine-Universität Düsseldorf
      • Urologische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
    • Universitätsklinikum des Saarlandes
      Homburg, Saarland, Germany
  • 1994–2012
    • University of Cologne
      • Department of Urology
      Köln, North Rhine-Westphalia, Germany
  • 2011
    • Maria Hilf Hospital, Daun
      Daun, Rheinland-Pfalz, Germany
  • 2010
    • Technische Universität Dresden
      • Klinik und Poliklinik für Urologie
      Dresden, Saxony, Germany
  • 2007
    • Universitätsklinikum Dresden
      Dresden, Saxony, Germany
  • 1999–2007
    • Philipps-Universität Marburg
      • Klinik für Urologie und Kinderurologie (Marburg)
      Marburg an der Lahn, Hesse, Germany
  • 2004
    • Martin Luther University of Halle-Wittenberg
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2002
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany
  • 1997–1998
    • Uniformed Services University of the Health Sciences
      • Department of Surgery
      Maryland, United States
  • 1993
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 1992
    • Bundeswehrzentralkrankenhaus Koblenz
      Coblenz, Rheinland-Pfalz, Germany