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Urethral cancer grows in the tube that carries urine out of the body, with fewer than one case per million people a year. With no randomised trials, it is treated by borrowing from bladder, anal or vulvar cancer depending on cell type and location; chemotherapy with radiotherapy before or instead of surgery lets more patients keep their organs.
Primary urethral carcinoma is defined by where in the urethra it starts and by the lining it arises from: urothelial carcinoma in the prostatic and proximal urethra, squamous cell carcinoma in the distal (penile or anterior) urethra, and adenocarcinoma, often of Skene or Littre gland origin or arising in a diverticulum, particularly in women. Risk factors include chronic stricture and inflammation, prior radiotherapy, urethral diverticulum and HPV infection for squamous tumours. Presentation is with bleeding, obstruction or a palpable mass, and diagnosis is frequently delayed because symptoms mimic stricture or infection.
There are no randomised trials. Distal tumours are treated with organ-sparing surgery (partial urethrectomy or distal penectomy in men; distal urethrectomy in women) or with radiotherapy; proximal and locally advanced tumours have historically required radical cystoprostatectomy or anterior exenteration, but the modern approach favours neoadjuvant or definitive platinum-based chemotherapy with or without radiotherapy, extrapolated from bladder cancer (cisplatin-based combinations for urothelial histology) and anal or vulvar cancer (mitomycin or cisplatin with fluorouracil and radiotherapy for squamous histology). Multi-institutional series such as those from the international collaboration on primary urethral carcinoma show better survival with multimodal therapy than with surgery alone, and the EAU has published a dedicated guideline.
The practical frontier is applying advances from urothelial cancer (enfortumab vedotin with pembrolizumab, checkpoint inhibitors) and HPV-associated squamous cancers to this tiny population through basket trials and registries.
One of the rarest genitourinary cancers, with fewer than one case per million per year in most registries; it is more common in men and in people over 60.
Renal cell carcinoma comes from the kidney's filtering cortex, urothelial cancer from the lining of the collecting system and bladder, and the adrenal on top hosts cortical and medullary (neuroblastoma) tumours.
Same organ: Collecting duct carcinoma of the kidney, Renal medullary carcinoma (SMARCB1-deficient), TFE3-rearranged (translocation) renal cell carcinoma, Fumarate hydratase-deficient renal cell carcinoma (HLRCC-associated), Succinate dehydrogenase-deficient renal cell carcinoma, Mucinous tubular and spindle cell carcinoma of the kidney, Eosinophilic solid and cystic renal cell carcinoma, Clear cell papillary renal cell tumour, Urothelial carcinoma of the urethra, Squamous cell carcinoma of the urethra, Adenocarcinoma of the urethra (including clear cell adenocarcinoma), Melanoma of the urethra, Non-muscle-invasive bladder cancer, Muscle-invasive and advanced bladder cancer, Bladder & urothelial cancer, Clear cell renal cell carcinoma, Papillary renal cell carcinoma, Chromophobe renal cell carcinoma, Renal cell carcinoma, Wilms tumour (nephroblastoma), Neuroblastoma (paediatric), Low-risk neuroblastoma (INRG very low and low risk, including stage MS), Intermediate-risk neuroblastoma, High-risk neuroblastoma, Adrenocortical carcinoma, Pheochromocytoma and paraganglioma (PPGL), Penile cancer, Localised penile cancer (organ-confined, node-negative), Node-positive and metastatic penile cancer, Localised adrenocortical carcinoma (ENSAT stage I to III, resectable), Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable), Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127), Metastatic pheochromocytoma and paraganglioma
Organ-sparing surgery (distal urethrectomy, partial penectomy) or radiotherapy including brachytherapy.
Neoadjuvant platinum-based chemotherapy (or chemoradiation for squamous histology) followed by surgery; definitive chemoradiation as organ-preserving alternative.
Treat by histology: urothelial-type regimens (enfortumab vedotin plus pembrolizumab, gemcitabine-cisplatin) or squamous regimens; clinical trials.
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Query for this cancer: (TITLE:"Urethral cancer" OR ABSTRACT:"Urethral cancer" OR TITLE:"Primary urethral carcinoma" OR ABSTRACT:"Primary urethral carcinoma" OR TITLE:"Carcinoma of the urethra" OR ABSTRACT:"Carcinoma of the urethra") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Urethral cancer, not a curated reading list.
Thiaudierre's description in a woman.
Gakis and colleagues pool multi-institutional data, showing benefit of perioperative chemotherapy and defining the EAU guideline.
Applied by extrapolation to urothelial-type urethral carcinoma.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
Temperature of 38 C or higher, or feeling shivery and unwell even without a fever. Antibody-drug conjugates suppress the bone marrow, and several carry a boxed warning for severe neutropenia.
Tingling, numbness or weakness that affects walking or using the hands; peripheral neuropathy is common with the vedotin (MMAE) payload and doses are reduced or stopped at grade 2 to 3.
Hyperglycaemia: hold if glucose above 13.9 mmol/L (250 mg/dL).
See all on the product pages:CisplatinEnfortumab vedotinFluorouracil (5-FU)Gemcitabine + cisplatinMitomycin CPembrolizumab·Printable cards in the navigator
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