Urachal Carcinoma

Urachal carcinoma is a rare malignancy that arises from the epithelium of the urachal remnant, forming in the extraperitoneal midline between the bladder dome and the umbilicus. It represents 0.35 to 0.7 percent of bladder cancers and about 20 to 40 percent of adenocarcinomas of the bladder. The incidence is about 1 in 5 million, and the mean age at diagnosis is 50 to 60 years, with a slight male predominance.

The tumour is often diagnosed late, because of its location and insidious symptoms.

Adenocarcinoma (enteric, mucinous, signet ring, or not otherwise specified) accounts for 80 to 90 percent. The others are urothelial, squamous cell, small cell and sarcomas. Typical molecular features are TP53 mutations, KRAS and BRAF mutations, and amplification of genes in the MAPK pathway, with frequent microsatellite stability.

Criteria for diagnosis:

• a tumour located in the bladder dome
• a sharp demarcation between the tumour and the surface epithelium
• absence of cystitis cystica or glandularis beyond the dome
• absence of a primary adenocarcinoma elsewhere
• invasion of the bladder wall or beyond with a urachal remnant

Staging:

• stage I: tumour confined to the urachal mucosa
• stage II: invasion confined to the urachus itself
• stage IIIA: local extension to the bladder
• stage IIIB: extension to abdominal wall
• stage IIIC: extension to peritoneum
• stage IIID: extension to other viscera
• stage IVA: lymph node metastasis
• stage IVB: distant metastasis

Five year survival is about 40 to 50 percent overall, with 90 percent for stage I and under 20 percent for stage IV.

• Haematuria (macroscopic, in about 70 percent), the most common presentation.
• Mucusuria (mucus in the urine), irritative urinary symptoms, suprapubic pain, and a palpable infraumbilical midline mass.
• Umbilical discharge (blood, mucus or pus) or umbilical mass.
• Weight loss, fatigue, and recurrent urinary tract infections.
• Metastatic disease: pelvic lymph nodes, lung, bone, liver, peritoneum.
• Pseudomyxoma peritonei in rare cases, from mucin spread.
• Often an incidental finding of a midline mass on imaging.

• Cystoscopy: a mass at the dome or anterior wall, with intact urothelium in many; biopsy with deep sampling for histology (adenocarcinoma with CDX2, CK20 and β-catenin positivity); the endoscopic appearance can mimic bladder cancer.
• CT or MRI of the abdomen and pelvis: midline supravesical mass along the urachal tract, with calcification in 50 to 70 percent (peripheral and stippled), cystic and solid components, extension into the retropubic space.
• Colonoscopy and gastrointestinal imaging to exclude metastatic colorectal adenocarcinoma, as the pathology is identical; a normal colonoscopy is required.
• Tumour markers: CEA and CA 19-9 are elevated in about 60 percent and used for follow up; CA-125 may be increased.
• Staging with CT chest, abdomen, pelvis, bone scan or PET-CT if required; urine cytology is often negative.

• Complete surgical resection is the only curative treatment: en bloc partial cystectomy with removal of the urachal ligament, the umbilicus, the posterior rectus sheath, the peritoneum overlying the tumour and a cuff of normal bladder with negative margins (2 cm), plus bilateral pelvic lymphadenectomy. Radical cystectomy is reserved for tumours at the trigone or bladder neck, multifocal disease, or when negative margins cannot be obtained with a partial resection.
• Frozen section margins at surgery. Avoid tumour spillage; avoid transurethral resection alone, which is inadequate.
• Adjuvant therapy: systemic chemotherapy is used for stage III or IV, node positive or margin positive disease. It is based on gastrointestinal adenocarcinoma regimens:
  • FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and 5-fluorouracil 400 mg/m2 bolus then 2,400 mg/m2 over 46 hours every 14 days) or FOLFIRI
  • 5-fluorouracil with cisplatin (5-fluorouracil 1,000 mg/m2 on days 1 to 5 with cisplatin 70 mg/m2 on day 1 every 3 weeks)
  • gemcitabine with cisplatin for non-adenocarcinoma histology
  Responses are partial and survival improvement is modest.
• Metastatic disease: palliative chemotherapy with FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 bolus then 2,400 mg/m2 over 46 hours every 14 days) or FOLFIRI.
• Targeted options depend on molecular testing. Anti-EGFR therapy is not used in KRAS-mutated tumours. Use BRAF or microsatellite-instability-guided therapy where appropriate, e.g. pembrolizumab 200 mg every 3 weeks for microsatellite instability high tumours.
• Cytoreductive surgery and intraperitoneal chemotherapy are options for peritoneal disease in selected patients.
• Radiotherapy has a limited role and is used for palliation of bone metastases or local recurrence.
• Surveillance: clinical review, CEA, cystoscopy and CT chest, abdomen and pelvis every 3 to 4 months in the first 2 years, then every 6 months to 5 years, then yearly; the majority of recurrences occur in the first 3 years.