Academic Center for Urogenital tumours

Last updated: 365 days ago.

  • https://www.erasmusmc.nl/cs-kankerinstituut/4339032/4642747/jaarverslag-urogenital-tumors
  • Multidisciplinary approach of fundamental research, care, and epidemiologics in Urogenital Tumours between Urology, Pathology, Radiotherapy, Medical Oncology, Public Health, Radiology, and Clinical Chemistry
  • Translation of results into the regional care paths of the comprehensive cancer network south west Netherlands and the Anser Prostate Cancer Network via patient care centres and Anser Prostate Cancer Centres.
  • Enforcing its existing unique Erasmus specific aspects in epidemiology (screening and risk assessment), biobanking (materials, databases, mondial IT network), care (Cyberknife, hyperthermia, theragnostics), imaging (analysis), drug models (chemo-resistancy), and marker development (precision medicine, marker patents

Academic Center of Excellence

Research Activities

The clinically orientated departments within the ACE conduct Phase 1,2,and 3 clinical trials related to Urogenital Tumours Fundamental and translational research projects are many, all multidisciplinary and most internationally, including:

  • Prostate: Optimization of screening tests and surveillance (genomic and exosomal urinary markers); development and validation of E-health solutions; optimizing individualized care by risk-based and shared decision making; Development of new diagnostic tools using 3D microscopy of prostate cancer architecture; developing treatments of micro and oligometastatic disease by theragnostics; new agents for precision medicine in castration resistant disease.
  • Bladder; Marker development in urine for screening and surveillance (methylation prognostic markers MDxHealth), genomic analysis of circulating tumor cells and tissues for treatment stratification and new treatments, developing the centre for bladder preservation, stem cell research directed at elimination of radioresistant tumour cells
  • Germ Cells: exploration of metabolic pathways and innovative biomarkers for detection and treatment stratification to prevent possible over-/undertreatment, and to predict tumour recurrences. These include both markers on the protein level, genomic markers, as well as on microRNAs to be investigated predominantly in body fluids. Scientists from various departments are involved in international epidemiological trials around prostate cancer (European Randomised study on Screening of Prostate Cancer, Prostate Cancer International Active Surveillance, Movember Global Action Plans 1-4), and germ cell cancer (Movember GAP 5, ERN rare urologic diseases). Co-promotorship of scientists from Erasmus departments and international universities are realized.

Type of

Collaborations

Co-promotorship of scientists from Erasmus departments and international universities are realized. These are illustrated in the annual reports, see below

Educational

Contributions

The ACE contributes to Ba, MSc, and PhD programs as illustrated in the Annual Reports, below. Regular quality control audits are be performed.

The ACE contributes to the Clinical Technology and NanoBiology programs within the Medical Delta, and has the intention of providing master-phase scholarships for technical developments within research and care.

The ACE has initiated integrated training tracks for young clinical scientists for translational research, illustrated in the Annual Reports.

Individual ACE members undergo SET Q and D-RECT at department level.

Patient

Care Activities

All care related to urogenital tumours within Erasmus MC has been labelled as academic according to the ROBIJN and NFU criteria. Erasmus MC is the referral centre for metastatic germ cell tumours, and has a long track record on surgical postchemotherapy treatment.

Erasmus MC is preferred partner for urogenital treatments for health care insurances. The research of Gonadal tumours is participating in the ERN rare diseases: Testicular tumours. Prostate and Bladder cancer care is participating in ICHOM and in Value based health care programs. Their clinical paths are defined, and incorporated in multidisciplinary tumour boards.

The development of digital dashboards for clinical decision making and algorithms is incorporated in a recent STW-KWF program. Prostate cancer care is evaluated within the IKNL audit of ProstaatPartners. Erasmus MC conducts many clinical trials (Medical Oncology, Urology, Radiotherapy) for the development and validation of novel and adjuvant drugs or innovative treatments (e.g. virolytic neoadjuvant therapy).

Societal Relevance to Research, Education and Patient Care

The ACE contributes to the news site DUOS, that connects physicians of 23 Dutch urologic oncologic centres to the most recent developments in uro-oncology, and organizing trials and annual scientific meetings.

Members of this ACE are directly participating in international guideline committees of ESMO (gonadal tumours) and EAU (prostate cancer), and they are involved in the specific tumour work groups of the national professional societies for Urology, Medical Oncology, Radiotherapy, and Pathology, as well as Radiology and Clinical Chemistry.

Members of this ACE produce all together about 200 peer reviewed papers annually related to urogenital tumours. The ACe involves (inter) national activities for screening of prostate cancer on a public level (connection with the ACE Prevention) as well as an individual level (Prostate Risk Calculator). Patents have been filed for exosomal prostate cancer markers (G. Jenster).

A Patient Advisory Board consisting of representatives of major patient advocacy organisations (Prostaat Kanker Stichting, Stichting Waterloop, Stichting Teelbalkanker) is installed as of September 1st, 2016 to connect to charity foundations (KWF, Alpe d'Huzes, Inspire 2 Live, Movember). Based on patient participation in the strategic meetings of the ACE, three patient driven projects have been defined in 2017, while in 2018 a fourth project has been added considering a national randomized trial on life style and diet in prostate cancer patients, supported by governments, food-industry, coaching institutes, and patient advocacy groups.

Viability of Research, Education and Patient Care

https://www.erasmusmc.nl/cs-kankerinstituut/4339032/4642747/jaarverslag-urogenital-tumors

Scheme of monthly research meetings of all participants for knowledge sharing and research opportunities since 2015, including notes, discussions, agendas, and visitor registration by dedicated secretary (Diana Brusik):

  1. Annual retraite meeting for strategics and shared projects since 2015
  2. Quarterly strategic meetings of all PIs on education, governance, international research opportunities, and talent scouting, since 2016
  3. Two-monthly grant application reviews since 2016 by Research Buro Sophia
  4. Two-weekly management team for governance since 2016
  5. Number of PhD: 38 of which 5 international. (3 scolarships from the Chinese SC program, 1 from PRO-NEST and one from the University of Berlin). All students participate in conferences and are productive with annual publications for their dissertations. Impact of Publications within Erasmus MC: impact score Medical Oncology: 2.39; Urology 2.02;

Key and relevant publications of the last five years

  • Zuiverloon TC, Nieuweboer AJ, Vekony H, Kirkels WJ, Bangma CH, Zwarthoff EC: Markers predicting response to bacillus calmette-guerin immunotherapy in high-risk bladder cancer patients: a systematic review. European urology 61:128-45, 2012.
  • Rijlaarsdam MA, Tax DMJ, Gillis AJM, Dorssers LCJ, Koestler DC, De Ridder J, Looijenga LHJ. Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors. PLOS ONE 2015: Apr 10;10(4):e0122146
  • Aluwini S, Pos F, Schimmel E, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): acute toxicity results from a randomised non-inferiority phase 3 trial. Lancet Oncol 2015; 16(3): 274-83
  • Saad F, Fizazi K, Jinga V, Efstathiou E, Fong PC, Hart LL, Jones R, McDermott R, Wirth M, Suzuki K, MacLean DB, Wang L, Akaza H, Nelson J, Scher HI, Dreicer R, Webb IJ, de Wit R; for the ELM-PC 4 investigators. Orteronel plus prednisone in patients with chemotherapy-ve metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial. Lancet Oncol. 2015 Mar;16(3):338-48. doi: 10.1016/S1470-2045(15)70027-6. Epub 2015 Feb 18.
  • De Jong M., Essers J., van Weerden W.M. Imaging preclinical tumour models: improving translational power. Nature Rev. Cancer 14, 481–493 (2014).
  • Attenuated XPC Expression Is Not Associated with Impaired DNA Repair in Bladder Cancer. PLoS One (2015), 10, e0126029. Naipal, K.A.T., Raams, A., Bruens, S.T., Brandsma, I., Verkaik, N.S., Jaspers, N.G.J., Hoeijmakers, J.H.J., van Leenders, G.J., Pothof, J., Kanaar, R., Boormans, J. and van Gent, D.C.
  • Bruinsma SM, Zhang L, Roobol MJ, Bangma CH, Steyerberg EW, Nieboer D, Van Hemelrijck M; Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) consortium. The Movember Foundation's GAP3 cohort: a profile of the largest global prostate cancer active surveillance database to date. BJU Int. 2017 Dec 15.
  • El-Sayed IY, Daher A, Destouches D, Firlej V, Kostallari E, Maillé P, Huet E, Haidar-Ahmad N, Jenster G, de la Taille A, Abou Merhi R, Terry S, Vacherot F. Extracellular vesicles released by mesenchymal-like prostate carcinoma cells modulate EMT state of recipient epithelial-like carcinoma cells through regulation of AR signaling. Cancer Lett. 2017 Dec 1;410:100-111.
  • Del Re M, Biasco E, Crucitta S, Derosa L, Rofi E, Orlandini C, Miccoli M, Galli L, Falcone A, Jenster GW, van Schaik RH, Danesi R. The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients. Eur Urol. 2017 Apr;71(4):680-687.
  • Alves IT, Cano D, Böttcher R, van der Korput H, Dinjens W, Jenster G, Trapman J. A mononucleotide repeat in PRRT2 is an important, frequent target of mismatch repair deficiency in cancer. Oncotarget. 2017 Jan 24;8(4):6043-6056.
  • IV Bijnsdorp, ME van Royen, GW Verhaegh, ES Martens-Uzunova . The Non-Coding Transcriptome of Prostate Cancer: Implications for Clinical Practice. Molecular diagnosis & therapy 21 (4), 385-400 (2017)
  • Nonnekens J, Chatalic KL, Molkenboer-Kuenen JD, Beerens CE, Bruchertseifer F, Morgenstern A, Veldhoven-Zweistra J, Schottelius M, Wester HJ, van Gent DC, van Weerden WM, Boerman OC, de Jong M, Heskamp S. 213Bi-Labeled Prostate-Specific Membrane Antigen-Targeting Agents Induce DNA Double-Strand Breaks in Prostate Cancer Xenografts. Cancer Biother Radiopharm. 2017 Mar;32(2):67-73. (2017)
  • Gayet M, Mannaerts CK, Nieboer D, Beerlage HP, Wijkstra H, Mulders PFA, Roobol MJ. Prediction of Prostate Cancer: External Validation of the ERSPC Risk Calculator in a Contemporary Dutch Clinical Cohort. Eur Urol Focus. 2016 Aug 4.pii: S2405-4569(16)30107-9. doi: 10.1016/j.euf.2016.07.007. [Epub ahead of print] PubMed PMID: 28753781. (2017)
  • Fleshner K, Carlsson SV, Roobol MJ. The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA. Nat Rev Urol. 2017 Jan;14(1):26-37. doi: 10.1038/nrurol.2016.251. Epub 2016 Dec 20. Review. PubMed PMID: 27995937; PubMed Central PMCID: PMC5341610 (2017)
  • Real-time Watchful Surveillance Looks Like Active Waiting. Bangma C, Roobol M. Eur Urol. 2017 Dec;72(6): PMID: 2882258 (2017)
  • Presence of invasive cribriform or intraductal growth at biopsy outperforms percentage grade 4 in predicting outcome of Gleason score 3+4=7 prostate cancer. Kweldam CF, Kümmerlin IP, Nieboer D, Steyerberg EW, Bangma CH, Incrocci L, van der Kwast TH, Roobol MJ, van Leenders GJ. Mod Pathol. 2017 Aug;30(8):1126-1132. PMID:28530220 (2017)
  • ‘Systematic Review of Testicular Tumour Size and Rete Testis Invasion as Prognostic Factors for the Risk of Relapse of Clinical Stage I Seminoma Testis Patients Under Surveillance’ Eur Urol 2017; Nov 20 [Epub ahead of print] Joost L. Boormans, Javier Mayor de Castro, Lorenzo Marconi, Yuhong Yuan, M. Pilar Laguna Pes, Carsten Bokemeyer, Nicola Nicolai, Ferran Algaba, Jan Oldenburg, Peter Albers (2017)
  • ‘Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.’ Seiler R, Ashab HA, Erho N, van Rhijn BW, Winters B, Douglas J, Van Kessel KE, Fransen van de Putte EE, Sommerlad M, Wang NQ, Choeurng V, Gibb EA, Palmer-Aronsten B, Lam LL, Buerki C, Davicioni E, Sjödahl G, Kardos J, Hoadley KA, Lerner SP, McConkey DJ, Choi W, Kim WY, Kiss B, Thalmann GN, Todenhöfer T, Crabb SJ, North S, Zwarthoff EC, Boormans JL, Wright J, Dall'Era M, van der Heijden MS, Black PC. Eur Urol 2017; [Epub ahead of print]
  • Beukers W, van der Keur KA, Kandimalla R, Vergouwe Y, Steyerberg EW, Boormans JL, Jensen JB, Lorente JA, Real FX, Segersten U, Orntoft TF, Malats N, Malmstrom PU, Dyrskjot L, Zwarthoff EC. FGFR3, TERT and OTX1 as urinary biomarker combination for surveillance of bladder cancer patients in a large prospective multicenter study. J Urol. 2017 Jun;197(6):1410-8. (2017)
  • van Agthoven T, Eijkenboom WMH, Looijenga LHJ microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients. Cell Oncol (Dordr). 2017 Aug;40(4):379-388. doi: 10.1007/s13402-017-0333-9. Epub 2017 Jun 13. (2017)
  • Wortel RC, Incrocci L, Pos FJ, van der Heide UA, Lebesque JV, Aluwini S, Witte MG, Heemsbergen WD. Late side effects after image-guided intensity modulated radiotherapy compared to 3D-conformal radiotherapy for prostate cancer: results from two prospective cohorts. Int J Radiat Oncol Biol Phys 2016;95:680-9.
  • Aluwini S, Pos F, Schimmel E, Krol S, van der Toorn PP, de Jager H, Ghidey AW, Heemsbergen W, Heijmen B, Incrocci L. Hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: late toxicity in the Dutch Randomized phase III Hypofractionation Trial (HYPRO). Lancet Oncol 2016;17:464-74.
  • van den Tempel N, Odijk H, van Holthe N, Naipal K, Raams A, Eppink B, van Gent DC, Hardillo J, Verduijn GM, Drooger JC, van Rhoon GC, Smedts DHPM, van Doorn HC, Boormans JL, Jager A, Franckena M, Kanaar R. Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies. Int J Hyperthermia. 2017 Jul 31:1-8.
  • Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial. Petrylak DP, de Wit R, Chi KN, Drakaki A, Sternberg CN, Nishiyama H, Castellano D, Hussain S, Fléchon A, Bamias A, Yu EY, van der Heijden MS, Matsubara N, Alekseev B, Necchi A, Géczi L, Ou YC, Coskun HS, Su WP, Hegemann M, Percent IJ, Lee JL, Tucci M, Semenov A, Laestadius F, Peer A, Tortora G, Safina S, Del Muro XG, Rodriguez-Vida A, Cicin I, Harputluoglu H, Widau RC, Liepa AM, Walgren RA, Hamid O, Zimmermann AH, Bell-McGuinn KM, Powles T; RANGE study investigators. Lancet. 2017 Nov 18;390(10109):2266-2277. doi: 10.1016/S0140-6736(17)32365-6. Epub 2017 Sep 12. PMID: 28916371 (2017)
  • Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials. Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, Saad F, de Wit R, Aftab DT, Hirmand M, Limon A, Fizazi K, Fleisher M, de Bono JS, Scher HI. J Clin Oncol. 2017 Dec 22:JCO2017752998. doi: 10.1200/JCO.2017.75.2998. [Epub ahead of print] PMID: 29272162 (2017)
  • Testosterone Diminishes Cabazitaxel Efficacy and Intratumoral Accumulation in a Prostate Cancer Xenograft Model. Mout L, de Wit R, Stuurman D, Verhoef E, Mathijssen R, de Ridder C, Lolkema M, van Weerden W. EBioMedicine. 2018 Jan;27:182-186. doi: 10.1016/j.ebiom.2017.12.024. Epub 2017 Dec 20. PubMed PMID: 29276148; PubMed Central PMCID: PMC5828553. (2017)
  • Efficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells. Onstenk W, Sieuwerts AM, Kraan J, Van M, Nieuweboer AJ, Mathijssen RH, Hamberg P, Meulenbeld HJ, De Laere B, Dirix LY, van Soest RJ, Lolkema MP, Martens JW, van Weerden WM, Jenster GW, Foekens JA, de Wit R, Sleijfer S. Eur Urol. 2015 Dec;68(6):939-45. doi: 10.1016/j.eururo.2015.07.007. Epub 2015 Jul 15. PubMed PMID: 26188394.
  • What Is the Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in Excluding Prostate Cancer at Biopsy? A Systematic Review and Meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel. Moldovan PC, Van den Broeck T, Sylvester R, Marconi L, Bellmunt J, van den Bergh RCN, Bolla M, Briers E, Cumberbatch MG, Fossati N, Gross T, Henry AM, Joniau S, van der Kwast TH, Matveev VB, van der Poel HG, De Santis M, Schoots IG, Wiegel T, Yuan CY, Cornford P, Mottet N, Lam TB, Rouvière O. Eur Urol. 2017 Aug;72(2):250-266. doi: 10.1016/j.eururo.2017.02.026. Epub 2017 Mar 21. (2017)
  • 68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology. Dalm SU, Bakker IL, de Blois E, Doeswijk GN, Konijnenberg MW, Orlandi F, Barbato D, Tedesco M, Maina T, Nock BA, de Jong M. J Nucl Med. 2017 Feb;58(2):293-299. (2017)
  • 213Bi-Labeled Prostate-Specific Membrane Antigen-Targeting Agents Induce DNA Double-Strand Breaks in Prostate Cancer Xenografts. Nonnekens J, Chatalic KL, Molkenboer-Kuenen JD, Beerens CE, Bruchertseifer F, Morgenstern A, Veldhoven-Zweistra J, Schottelius M, Wester HJ, van Gent DC, van Weerden WM, Boerman OC, de Jong M, Heskamp S (2017) .Cancer Biother Radiopharm. 32: 67-73. (2017)
  • Snaterse G, Visser JA, Arlt W, Hofland J. Circulating steroid hormone variations throughout different stages of prostate cancer. Endocr Relat Cancer. 2017 Nov;24(11):R403-R420. doi: 10.1530/ERC-17-0155. Epub 2017 Sep 18. Review. PubMed PMID: 28924064.
  • A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable. van Kessel KE, van de Werken HJ, Lurkin I, Ziel-van der Made AC, Zwarthoff EC, Boormans JL. PLoS One. 2017 Mar 20;12(3):e0174039. doi: 10.1371/journal.pone.0174039. ECollection 2017.
  • Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy. Mod Path. 2016. Kweldam CF, Kümmerlin IP, Nieboer D, Verhoef EI, Steyerberg EW, van der Kwast TH, Roobol MJ, van Leenders GJ.
  • Hiltemann S, Jenster G, Trapman J, van der Spek P, Stubbs A. Discriminating somatic and germline mutations in tumor DNA samples without matching normals. Genome Res. 2015 Sep;25(9):1382-90
  • Screening for prostate cancer: results of the Rotterdam section of the European randomized study of screening for prostate cancer. Roobol MJ, Kranse R, Bangma CH, van Leenders AG, Blijenberg BG, van Schaik RH, Kirkels WJ, Otto SJ, van der Kwast TH, de Koning HJ,Schröder FH; ERSPC Rotterdam Study Group. Eur Urol. 2013 Oct;64(4):530-9.
  • Identification of TDRD1. as a direct target gene of ERG in primary prostate cancer. Boormans JL, Korsten H, Ziel – van der Made AJC, van Leenders GJLH, de Vos CV, Jenster G, Trapman J. Int J Cancer 2013;133:335-45.

PhD theses of the last five years

  • Giovanny Rodriguez Blanco - The Arachidonic Acid Pathway: A potential application in the diagnosis and prognosis of prostate cancer, 2017
  • Leonard Bokhorst - Prostate Cancer Screening and Active Surveillance, 2016
  • Hendrik Bergsma - Peptide Receptor Radionuclide Therapy & Oncology, 2017
  • Ines Teles Alves Characterization of Novel Genetic Alterations in Prostate Cancer (2015)
  • L. Venderbos, Quality of Life and Risk Stratification in Active Surveillance, 2015, December 2
  • T.C.M. Zuiverloon, Molecular diagnosis in Bladder Cancer, September 4, 2013
  • J. Kaprova. 2015. Malignant germ cell tumors and disorders of sex development: towards clinical implementation. (Promotor Looijenga)
  • Dr. G. van der Wielen: Erectile dysfunction after external beam radiotherapy for prostate cancer.
  • Robert J. van Soest, 2015 Sept. 9. Taxanes and Novel Androgen Receptor Targeted Agents in the Management of Metastatic Castration-Resistant Prostate Cancer.
  • Karin Schroten-Loef, Dept Urology, Erasmus MC-Cancer Institute. Thesis: ‘Interleukin 7 and patient selection in immunotherapy for prostate cancer’. Thesis defence: Jan 13th 2013. Acted as co-supervisor
  • Kristell Chatalic Novel ligands for prostate cancer imaging and therapy March 2016
  • Leonard Bokhorst, Prostate Cancer Screening and Active Surveillance, 2016
  • Local control of steroid hormone biosynthesis. J. Hofland. 30-05-2016

Non-scientific publications related to the ACE

  • annual report 2016 https://www.erasmusmc.nl/cs-kankerinstituut/4339032/4642747/jaarverslag-urogenital-tumors
  • Onderzoek van de lange adem CH Bangma, Medisch Contact 27 dec. 2017; www.medischcontact.nl/nieuws/laatste-nieuws/.../onderzoek-van-de-lange-adem.htm
  • Annual report AC Urogenital Tumours 2017 https://www.erasmusmc.nl/47659/51026/Jaarverslag2017.pdf
  • https://www.erasmusmc.nl/kankerinstituut/nieuws/2018/2018-10/Jaarverslag_2017_Academisch_Centrum_Urogenitale_tumoren/

Principal coordinator(s)