Urachal cancer - current concepts of a rare cancer

Urachal cancer is arare 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 amultidisciplinary approach. The non-cystic variant accounts for the majority of cases (83%), is more common in men (63%), shows amedian age at diagnosis of 51years and has a5-year survival rate of about 50%. In organ-confined disease, usually apartial 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 abiological 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 adistinct entity on the molecular level with closer resemblance to colorectal adenocarcinomas than to urothelial carcinomas.