Abstract
Urachal cancer is a rare but aggressive disease. In addition to the non-glandular tumors, non-cystic urachal adenocarcinomas are nowadays distinguished from the primary cystic variant. (Immunohistochemical) markers are only of minor differential diagnostic value and, therefore, the diagnosis is primarily established in a multidisciplinary approach. The non-cystic variant accounts for the majority of cases (83%), is more common in men (63%), shows a median age at diagnosis of 51 years and has a 5-year survival rate of about 50%. In organ-confined disease, usually a partial cystectomy of the tumor in the bladder dome, including the median umbilical ligament and umbilicus, is performed. In advanced stages, systemic therapy is needed while 5‑fuorouracil (5-FU) containing regimes have been shown to be more effective. Due to the rarity of the tumor, targeted therapy approaches based on a biological rationale are becoming increasingly relevant. As molecular data are still sparse, we compiled and analyzed the largest urachal cancer cohort to date. In 31% of the cases, MAPK-/PI3K signaling pathway alterations were detected (especially in K-/NRAS) with implications for anti-EGFR therapy approaches. Further potentially therapeutic alterations were detected in FGFR1, MET, PDGFRA, and erbB2/HER2. Additionally, PD-L1 tumor cell expression (clone: 22C3) was demonstrated in 16% of cases, therefore making anti-PD-1/PD-L1 immuno-oncological approaches worth considering despite the absence of mismatch repair deficiency (MMR-d) and/or high microsatellite instability (MSI-h). Finally, urachal adenocarcinomas seem to be a distinct entity on the molecular level with closer resemblance to colorectal adenocarcinomas than to urothelial carcinomas.
Zusammenfassung
Das Urachuskarzinom ist ein seltener aber aggressiver Tumor. Neben den nichtglandulären Tumoren wird heutzutage das primär zystische vom nichtzystischen Urachus-Adenokarzinom abgegrenzt. (Immunhistochemische) Marker sind in der Differentialdiagnose nur von begrenztem Nutzen, sodass die Diagnose primär multidisziplinär gestellt wird. Das nichtzystische Adenokarzinom (83 %) ist häufiger bei Männern (63 %), zeigt ein medianes Erkrankungsalter von 51 Jahren und eine 5‑Jahres-Überlebensrate von etwa 50 %. Im lokal begrenzten Stadium wird zumeist eine Resektion des tumortragenden Harnblasendaches sowie des medianen umbilikalen Ligaments und des Umbilicus angestrebt. In fortgeschrittenen Stadien bzw. Rezidiven ist eine chemotherapeutische Systemtherapie notwendig, wobei sich 5‑Fluorouracil-(5-FU-)haltige Regime als sinnvoll erwiesen haben. Bei der Seltenheit des Tumors kommt zielgerichteten Therapieversuchen – aufbauend auf einer biologischen Rationale – eine besondere Bedeutung zu. Bei bislang spärlichen Daten haben wir die bislang größte Urachuskarzinomkohorte kooperativ zusammengestellt und analysiert. In 31 % der Fälle zeigten sich Veränderungen der MAPK-/PI3K-Signalwege (bes. K-/NRAS) mit entsprechenden Implikationen für eine anti-EGFR-Therapie. Weitere potentiell therapeutisch nutzbare Veränderungen zeigten sich in FGFR1, MET, PDGFRA und erbB2/HER2. Zudem war eine PD-L1-Tumorzellexpression (Klon: 22C3) bei 16 % der Fälle vorhanden, sodass trotz des Fehlens einer MMR-d(„mismatch repair deficiency“)-/MSI-h(„high microsatellite instability“)-Situation immunonkologische Therapieversuche bedenkenswert erscheinen. Zuletzt ist das Urachuskarzinom eine molekular eigenständige Entität mit größerer Ähnlichkeit zum kolorektalen Adenokarzinom als zum Urothelkarzinom.
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H. Reis and T. Szarvas declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
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Reis, H., Szarvas, T. Urachal cancer—current concepts of a rare cancer. Pathologe 40 (Suppl 1), 31–39 (2019). https://doi.org/10.1007/s00292-018-0516-9
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DOI: https://doi.org/10.1007/s00292-018-0516-9