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42. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

02. - 04.06.2016, Augsburg

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A 2-gene panel derived from prostate cancer-enhanced transcripts in whole blood is prognostic for survival and predicts treatment benefit in metastatic castration-resistant prostate cancer

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  • M.M. Heck - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany
  • M. Thalgott - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany
  • S.C. Schmid - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany
  • W.K. Oh - Mount Sinai Hospital, The Tisch Cancer Institute, Department of Hematology/Oncology, New York, United States
  • Y. Gong - Mount Sinai Hospital, The Tisch Cancer Institute, Department of Hematology/Oncology, New York, United States
  • L. Wang - The Tisch Cancer Institute, Genetic and Genomic Sciences, New York, United States
  • J. Zhu - The Tisch Cancer Institute, Genetic and Genomic Sciences, New York, United States
  • A.-K. Seitz - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany
  • D. Porst - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany
  • M. Höppner - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany
  • M. Retz - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany
  • J.E. Gschwend - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany
  • R. Nawroth - Klinikum rechts der Isar der Technischen Universität München, Klinik für Urologie, München, Germany

Bayerische Urologenvereinigung. Österreichische Gesellschaft für Urologie und Andrologie. 42. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie. Augsburg, 02.-04.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocFV44

doi: 10.3205/16urobay044, urn:nbn:de:0183-16urobay0445

Published: April 20, 2016

© 2016 Heck et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: To determine a prognostic model derived from prostate cancer-enhanced transcripts in whole blood of castration-resistant prostate cancer (CRPC) patients and explore its applicability as a surrogate of treatment response.

Patients and methods: Six out of 23 selected transcripts were identified as specific for detection of metastatic prostate cancer cells in peripheral blood using quantitative polymerase chain reaction (qPCR). Their prognostic value was explored in whole blood samples of a training cohort (n=22 CRPC patients, New York, USA). A resulting 2-gene panel (2GP) including KLK2 and TMPRSS2 was validated in an independent cohort with pretreatment and posttreatment blood draws after 9-16 weeks of systemic treament (n=86 CRPC patients, Munich, Germany). Overall survival (OS), prostate-specific antigen-progression-free survival (PSA-PFS) and clinical PFS were analyzed. Kaplan Meier and cox regression analyses were performed.

Results: An unfavourable 2GP (≥1 marker positive) identified patients with poor survival (median OS 10.0 months [95%CI 5.7-14.2] vs. not reached; p=0.023). This was validated in an independent cohort at pretreatment (median OS 7.8 [95%CI 6.5-9.2] vs. 17.3 months [95%CI 10.7-23.8]; p=0.004) and posttreatment blood draw (median OS 5.0 [95%CI 0.0-10.0] vs. 18.0 months [95%CI 9.5-26.6]; p=0.003). The 2GP independently predicted OS on multivariate analysis (hazard ratio 2.1 [95%CI 1.1-4.0]; p=0.034) and performed better than PSA decline at correlation with OS.

Conversion to favourable 2GP during treatment correlated with improved OS, PSA-PFS and clinical PFS.

Conclusions: The established 2GP is prognostic for survival at pre- and posttreatment blood draw in CRPC patients and conversion to favourable 2GP predicts treatment benefit.