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Prädiktive Biomarker in der onkologischen Uropathologie

Predictive biomarkers in oncologic uropathology

  • Schwerpunkt: Präzisionsonkologie
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Zusammenfassung

Hintergrund

Urologische Tumoren zählen zu den häufigsten malignen Erkrankungen. In den letzten Jahren hat das Wissen um die molekularen Hintergründe und damit auch die potenzielle Zahl an prädiktiven Biomarkern deutlich zugenommen.

Ziel der Arbeit

Ziel der vorliegenden Arbeit ist es, eine Übersicht über aktuelle (molekulare) Entwicklungen und die damit verbundenen prädiktiven Biomarker in der urologischen Onkologie zu geben sowie einen Ausblick auf die kommenden Entwicklungen zu formulieren.

Material und Methoden

Es wurden die aktuelle Literatur und (Studien‑)Datenlage sowie eigene Erfahrungen berücksichtigt und zu Tumoren des ableitenden Harnsystems, der Niere und Prostata zusammengefasst.

Ergebnisse und Diskussion

Die molekularen Subtypen des muskelinvasiven Urothelkarzinoms der Harnblase (MIBC) zeigen eine prädiktive und prognostische Bedeutung mit klinikopathologischem Korrelat. Die Immuntherapie mit Checkpointinhibitoren (CPI) spielt besonders beim Urothelkarzinom, aber auch beim Nierenzellkarzinom und einer Subgruppe des Prostatakarzinoms eine Rolle. Bisher ist dabei lediglich die Erstlinientherapie des Urothelkarzinoms an die PD-L1-Expression gebunden (≥IC2/3, CPS ≥ 10). Weitere prädiktive Marker zur CPI-Therapie sind unter Evaluation, wobei die Wertigkeit der Tumormutationslast (TMB) noch nicht abschließend geklärt ist. Neben weiteren Subgruppen auch der Nierenzellkarzinome stellen Prostatakarzinome mit Veränderungen in den DNA-Reparaturmechanismen eine besondere klinische Gruppe mit speziellen Therapieoptionen dar (PARP-Inhibition, platinhaltige Chemotherapie). Die Vielzahl der potenziell therapierelevanten molekularen Veränderungen und damit verbundenen prädiktiven Marker macht differenzierte Genpanelanalysen sinnvoll, was in der urologischen Pathologie zu einer immer stärkeren Dynamik führt.

Abstract

Background

Tumors of the genitourinary system are common. In recent years, our understanding of their molecular background and therefore the number of potential predictive biomarkers has massively increased.

Objectives

The aim of the current work is to give an overview of recent (molecular) developments and predictive biomarkers in urologic oncology and to give a perspective of what might become relevant in the future of the field.

Material and methods

We considered the recent literature and study data and combined it with our own expertise in tumors of the urinary system, kidneys, and prostate.

Results and conclusions

The molecular subtypes of muscle-invasive urothelial bladder cancer (MIBC) hold a predictive and prognostic significance and correlate with clinicopathological features. Immune therapy with checkpoint inhibitors (CPI) has a major role in urothelial carcinoma (UC), but also in renal cell carcinoma and a subgroup of prostate cancers. The first-line use in UC is restricted to PD-L1-“positive” cases (≥IC2/3, CPS ≥ 10). Further predictive markers are currently under evaluation, while the predictive significance of tumor mutational burden (TMB) is under debate. In addition to a subgroup of renal cell carcinomas, a subgroup of prostate carcinomas with alterations in the DNA repair system might benefit from a customized therapy approach (PARP inhibitors, platin-containing chemotherapy). The multitude of potentially therapy-relevant molecular alterations and related predictive biomarkers calls for the implementation of sophisticated molecular analyses in daily routine. This will lead to an even more rapid dynamic in the field of genitourinary pathology.

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Funding

Förderung

Mit Unterstützung durch das ungarische Wissenschafts‑, Entwicklungs- und Innovationsministerium (NKFIH/FK 12443, NVKP_16-1-2016-004, ÙNKP-18-4-SE-66). T. Szarvas hat ein János-Bolyai-Forschungsstipendium von der ungarischen Akademie der Wissenschaften erhalten.

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Authors and Affiliations

  1. Institut für Pathologie, Westdeutsches Tumorzentrum Essen, Universitätsmedizin Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Deutschland

    H. Reis

  2. Klinik für Urologie, Westdeutsches Tumorzentrum Essen, Universitätsmedizin Essen, Universität Duisburg-Essen, Essen, Deutschland

    T. Szarvas

  3. Klinik für Urologie, Semmelweis-Universität, Budapest, Ungarn

    T. Szarvas

  4. Interdisziplinäre Uroonkologie des Westdeutschen Tumorzentrums Essen, Klinik für Urologie, Innere Medizin (Tumorforschung), Universitätsmedizin Essen, Universität Duisburg-Essen, Essen, Deutschland

    V. Grünwald

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Correspondence to H. Reis.

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Interessenkonflikt

H. Reis: Honorare von Roche, Bristol-Myer Squibb. Forschungsunterstützung von Bristol-Myer Squibb. V. Grünwald: Berater für Pfizer, Novartis, Bristol-Myer Squibb, Ipsen, Eisai, EUSAPharm, MSD, Merck Serono, Lilly und Roche. Honorare von AstraZeneca, Pfizer, Novartis, Bristol-Myer Squibb, MSD, Ipsen, Eisai, Lilly und Roche. Aktien von AstraZeneca, Bristol-Myer Squibb und MSD. Forschungsunterstützung von Bristol-Myer Squibb, MSD, AstraZeneca, Pfizer und Novartis. T. Szarvas: Honorare von Sandoz.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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K. W. Schmid, Essen

H. A. Baba, Essen

H.-U. Schildhaus, Essen

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Reis, H., Szarvas, T. & Grünwald, V. Prädiktive Biomarker in der onkologischen Uropathologie. Pathologe 40, 264–275 (2019). https://doi.org/10.1007/s00292-019-0606-3

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